an essay about dna

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Who discovered the structure of DNA?

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• National Center for Biotechnology Information - The Structure and Function of DNA
• Khan Academy - DNA
• Healthline - DNA explained and explored
• Biology LibreTexts - DNA
• Live Science - DNA: Definition, Structure & Discovery
• Genetic Home Reference - What Is DNA?
• National Human Genome Research Institute - Deoxyribonucleic Acid (DNA) fact sheet
• Nature - What Rosalind Franklin truly contributed to the discovery of DNA’s structure
• DNA - Children's Encyclopedia (Ages 8-11)
• DNA - Student Encyclopedia (Ages 11 and up)

What does DNA do?

Deoxyribonucleic acid (DNA) is an organic chemical that contains genetic information and instructions for protein synthesis . It is found in most cells of every organism. DNA is a key part of reproduction in which genetic heredity occurs through the passing down of DNA from parent or parents to offspring.

What is DNA made of?

DNA is made of nucleotides . A nucleotide has two components: a backbone, made from the sugar deoxyribose and phosphate groups, and nitrogenous bases, known as cytosine , thymine , adenine , and guanine . Genetic code is formed through different arrangements of the bases.

The discovery of DNA’s double-helix structure is credited to the researchers James Watson and Francis Crick , who, with fellow researcher Maurice Wilkins , received a Nobel Prize in 1962 for their work. Many believe that Rosalind Franklin should also be given credit, since she made the revolutionary photo of DNA’s double-helix structure, which was used as evidence without her permission.

Can you edit DNA?

Gene editing today is mostly done through a technique called Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), adopted from a bacterial mechanism that can cut out specific sections in DNA. One use of CRISPR is the creation of genetically modified organism (GMO) crops.

What’s the difference between DNA and RNA?

DNA is the master blueprint for life and constitutes the genetic material in all free-living organisms. RNA uses DNA to code for the structure of proteins synthesized in cells . Learn more about the differences between DNA and RNA.

Recent News

DNA , organic chemical of complex molecular structure that is found in all prokaryotic and eukaryotic cells and in many viruses . DNA codes genetic information for the transmission of inherited traits.

A brief treatment of DNA follows. For full treatment, see genetics: DNA and the genetic code .

The chemical DNA was first discovered in 1869, but its role in genetic inheritance was not demonstrated until 1943. In 1953 James Watson and Francis Crick , aided by the work of biophysicists Rosalind Franklin and Maurice Wilkins , determined that the structure of DNA is a double-helix polymer , a spiral consisting of two DNA strands wound around each other. The breakthrough led to significant advances in scientists’ understanding of DNA replication and hereditary control of cellular activities.

Each strand of a DNA molecule is composed of a long chain of monomer nucleotides . The nucleotides of DNA consist of a deoxyribose sugar molecule to which is attached a phosphate group and one of four nitrogenous bases : two purines ( adenine and guanine ) and two pyrimidines ( cytosine and thymine ). The nucleotides are joined together by covalent bonds between the phosphate of one nucleotide and the sugar of the next, forming a phosphate-sugar backbone from which the nitrogenous bases protrude. One strand is held to another by hydrogen bonds between the bases; the sequencing of this bonding is specific—i.e., adenine bonds only with thymine, and cytosine only with guanine.

The configuration of the DNA molecule is highly stable, allowing it to act as a template for the replication of new DNA molecules, as well as for the production ( transcription ) of the related RNA (ribonucleic acid) molecule. A segment of DNA that codes for the cell’s synthesis of a specific protein is called a gene .

DNA replicates by separating into two single strands, each of which serves as a template for a new strand. The new strands are copied by the same principle of hydrogen-bond pairing between bases that exists in the double helix. Two new double-stranded molecules of DNA are produced, each containing one of the original strands and one new strand. This “semiconservative” replication is the key to the stable inheritance of genetic traits.

Within a cell, DNA is organized into dense protein-DNA complexes called chromosomes . In eukaryotes , the chromosomes are located in the nucleus , although DNA also is found in mitochondria and chloroplasts . In prokaryotes , which do not have a membrane-bound nucleus, the DNA is found as a single circular chromosome in the cytoplasm . Some prokaryotes, such as bacteria , and a few eukaryotes have extrachromosomal DNA known as plasmids , which are autonomous , self-replicating genetic material. Plasmids have been used extensively in recombinant DNA technology to study gene expression.

The genetic material of viruses may be single- or double-stranded DNA or RNA. Retroviruses carry their genetic material as single-stranded RNA and produce the enzyme reverse transcriptase , which can generate DNA from the RNA strand. Four-stranded DNA complexes known as G-quadruplexes have been observed in guanine-rich areas of the human genome .

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Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002.

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Molecular Biology of the Cell. 4th edition.

The structure and function of dna.

Biologists in the 1940s had difficulty in accepting DNA as the genetic material because of the apparent simplicity of its chemistry. DNA was known to be a long polymer composed of only four types of subunits, which resemble one another chemically. Early in the 1950s, DNA was first examined by x-ray diffraction analysis, a technique for determining the three-dimensional atomic structure of a molecule (discussed in Chapter 8). The early x-ray diffraction results indicated that DNA was composed of two strands of the polymer wound into a helix. The observation that DNA was double-stranded was of crucial significance and provided one of the major clues that led to the Watson-Crick structure of DNA. Only when this model was proposed did DNA's potential for replication and information encoding become apparent. In this section we examine the structure of the DNA molecule and explain in general terms how it is able to store hereditary information.

• A DNA Molecule Consists of Two Complementary Chains of Nucleotides

A DNA molecule consists of two long polynucleotide chains composed of four types of nucleotide subunits. Each of these chains is known as a DNA chain , or a DNA strand . Hydrogen bonds between the base portions of the nucleotides hold the two chains together ( Figure 4-3 ). As we saw in Chapter 2 ( Panel 2-6 , pp. 120-121), nucleotides are composed of a five-carbon sugar to which are attached one or more phosphate groups and a nitrogen-containing base. In the case of the nucleotides in DNA, the sugar is deoxyribose attached to a single phosphate group (hence the name deoxyribonucleic acid ), and the base may be either adenine (A), cytosine (C), guanine ( G ), or thymine (T) . The nucleotides are covalently linked together in a chain through the sugars and phosphates, which thus form a “backbone” of alternating sugar-phosphate-sugar-phosphate (see Figure 4-3 ). Because only the base differs in each of the four types of subunits, each polynucleotide chain in DNA is analogous to a necklace (the backbone) strung with four types of beads (the four bases A, C, G, and T). These same symbols (A, C, G, and T) are also commonly used to denote the four different nucleotides—that is, the bases with their attached sugar and phosphate groups.

DNA and its building blocks. DNA is made of four types of nucleotides, which are linked covalently into a polynucleotide chain (a DNA strand) with a sugar-phosphate backbone from which the bases (A, C, G, and T) extend. A DNA molecule is composed of two (more...)

The way in which the nucleotide subunits are lined together gives a DNA strand a chemical polarity. If we think of each sugar as a block with a protruding knob (the 5′ phosphate) on one side and a hole (the 3′ hydroxyl ) on the other (see Figure 4-3 ), each completed chain, formed by interlocking knobs with holes, will have all of its subunits lined up in the same orientation. Moreover, the two ends of the chain will be easily distinguishable, as one has a hole (the 3′ hydroxyl) and the other a knob (the 5′ phosphate) at its terminus. This polarity in a DNA chain is indicated by referring to one end as the 3 ′ end and the other as the 5 ′ end .

The three-dimensional structure of DNA — the double helix —arises from the chemical and structural features of its two polynucleotide chains. Because these two chains are held together by hydrogen bonding between the bases on the different strands, all the bases are on the inside of the double helix, and the sugar -phosphate backbones are on the outside (see Figure 4-3 ). In each case, a bulkier two-ring base (a purine ; see Panel 2-6 , pp. 120–121) is paired with a single-ring base (a pyrimidine ); A always pairs with T, and G with C ( Figure 4-4 ). This complementary base-pairing enables the base pairs to be packed in the energetically most favorable arrangement in the interior of the double helix. In this arrangement, each base pair is of similar width, thus holding the sugar-phosphate backbones an equal distance apart along the DNA molecule . To maximize the efficiency of base-pair packing, the two sugar-phosphate backbones wind around each other to form a double helix, with one complete turn every ten base pairs ( Figure 4-5 ).

Complementary base pairs in the DNA double helix. The shapes and chemical structure of the bases allow hydrogen bonds to form efficiently only between A and T and between G and C, where atoms that are able to form hydrogen bonds (see Panel 2-3, pp. 114–115) (more...)

The DNA double helix. (A) A space-filling model of 1.5 turns of the DNA double helix. Each turn of DNA is made up of 10.4 nucleotide pairs and the center-to-center distance between adjacent nucleotide pairs is 3.4 nm. The coiling of the two strands around (more...)

The members of each base pair can fit together within the double helix only if the two strands of the helix are antiparallel —that is, only if the polarity of one strand is oriented opposite to that of the other strand (see Figures 4-3 and 4-4 ). A consequence of these base-pairing requirements is that each strand of a DNA molecule contains a sequence of nucleotides that is exactly complementary to the nucleotide sequence of its partner strand.

• The Structure of DNA Provides a Mechanism for Heredity

Genes carry biological information that must be copied accurately for transmission to the next generation each time a cell divides to form two daughter cells. Two central biological questions arise from these requirements: how can the information for specifying an organism be carried in chemical form, and how is it accurately copied? The discovery of the structure of the DNA double helix was a landmark in twentieth-century biology because it immediately suggested answers to both questions, thereby resolving at the molecular level the problem of heredity. We discuss briefly the answers to these questions in this section , and we shall examine them in more detail in subsequent chapters.

DNA encodes information through the order, or sequence, of the nucleotides along each strand. Each base —A, C, T, or G —can be considered as a letter in a four-letter alphabet that spells out biological messages in the chemical structure of the DNA. As we saw in Chapter 1, organisms differ from one another because their respective DNA molecules have different nucleotide sequences and, consequently, carry different biological messages. But how is the nucleotide alphabet used to make messages, and what do they spell out?

As discussed above, it was known well before the structure of DNA was determined that genes contain the instructions for producing proteins. The DNA messages must therefore somehow encode proteins ( Figure 4-6 ). This relationship immediately makes the problem easier to understand, because of the chemical character of proteins. As discussed in Chapter 3, the properties of a protein , which are responsible for its biological function, are determined by its three-dimensional structure, and its structure is determined in turn by the linear sequence of the amino acids of which it is composed. The linear sequence of nucleotides in a gene must therefore somehow spell out the linear sequence of amino acids in a protein. The exact correspondence between the four-letter nucleotide alphabet of DNA and the twenty-letter amino acid alphabet of proteins—the genetic code —is not obvious from the DNA structure, and it took over a decade after the discovery of the double helix before it was worked out. In Chapter 6 we describe this code in detail in the course of elaborating the process, known as gene expression , through which a cell translates the nucleotide sequence of a gene into the amino acid sequence of a protein.

The relationship between genetic information carried in DNA and proteins.

The complete set of information in an organism's DNA is called its genome , and it carries the information for all the proteins the organism will ever synthesize. (The term genome is also used to describe the DNA that carries this information.) The amount of information contained in genomes is staggering: for example, a typical human cell contains 2 meters of DNA. Written out in the four-letter nucleotide alphabet, the nucleotide sequence of a very small human gene occupies a quarter of a page of text ( Figure 4-7 ), while the complete sequence of nucleotides in the human genome would fill more than a thousand books the size of this one. In addition to other critical information, it carries the instructions for about 30,000 distinct proteins.

The nucleotide sequence of the human β-globin gene. This gene carries the information for the amino acid sequence of one of the two types of subunits of the hemoglobin molecule, which carries oxygen in the blood. A different gene, the α-globin (more...)

At each cell division , the cell must copy its genome to pass it to both daughter cells. The discovery of the structure of DNA also revealed the principle that makes this copying possible: because each strand of DNA contains a sequence of nucleotides that is exactly complementary to the nucleotide sequence of its partner strand, each strand can act as a template , or mold, for the synthesis of a new complementary strand. In other words, if we designate the two DNA strands as S and S′, strand S can serve as a template for making a new strand S′, while strand S′ can serve as a template for making a new strand S ( Figure 4-8 ). Thus, the genetic information in DNA can be accurately copied by the beautifully simple process in which strand S separates from strand S′, and each separated strand then serves as a template for the production of a new complementary partner strand that is identical to its former partner.

DNA as a template for its own duplication. As the nucleotide A successfully pairs only with T, and G with C, each strand of DNA can specify the sequence of nucleotides in its complementary strand. In this way, double-helical DNA can be copied precisely. (more...)

The ability of each strand of a DNA molecule to act as a template for producing a complementary strand enables a cell to copy, or replicate , its genes before passing them on to its descendants. In the next chapter we describe the elegant machinery the cell uses to perform this enormous task.

• In Eucaryotes, DNA Is Enclosed in a Cell Nucleus

Nearly all the DNA in a eucaryotic cell is sequestered in a nucleus , which occupies about 10% of the total cell volume. This compartment is delimited by a nuclear envelope formed by two concentric lipid bilayer membranes that are punctured at intervals by large nuclear pores, which transport molecules between the nucleus and the cytosol . The nuclear envelope is directly connected to the extensive membranes of the endoplasmic reticulum . It is mechanically supported by two networks of intermediate filaments: one, called the nuclear lamina , forms a thin sheetlike meshwork inside the nucleus, just beneath the inner nuclear membrane ; the other surrounds the outer nuclear membrane and is less regularly organized ( Figure 4-9 ).

A cross-sectional view of a typical cell nucleus. The nuclear envelope consists of two membranes, the outer one being continuous with the endoplasmic reticulum membrane (see also Figure 12-9). The space inside the endoplasmic reticulum (the ER lumen) (more...)

The nuclear envelope allows the many proteins that act on DNA to be concentrated where they are needed in the cell, and, as we see in subsequent chapters, it also keeps nuclear and cytosolic enzymes separate, a feature that is crucial for the proper functioning of eucaryotic cells. Compartmentalization, of which the nucleus is an example, is an important principle of biology; it serves to establish an environment in which biochemical reactions are facilitated by the high concentration of both substrates and the enzymes that act on them.

Genetic information is carried in the linear sequence of nucleotides in DNA . Each molecule of DNA is a double helix formed from two complementary strands of nucleotides held together by hydrogen bonds between G -C and A-T base pairs. Duplication of the genetic information occurs by the use of one DNA strand as a template for formation of a complementary strand. The genetic information stored in an organism's DNA contains the instructions for all the proteins the organism will ever synthesize. In eucaryotes, DNA is contained in the cell nucleus .

• Cite this Page Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. The Structure and Function of DNA.
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9.1 The Structure of DNA

Learning objectives.

• Describe the structure of DNA
• Describe how eukaryotic and prokaryotic DNA is arranged in the cell

In the 1950s, Francis Crick and James Watson worked together at the University of Cambridge, England, to determine the structure of DNA. Other scientists, such as Linus Pauling and Maurice Wilkins, were also actively exploring this field. Pauling had discovered the secondary structure of proteins using X-ray crystallography. X-ray crystallography is a method for investigating molecular structure by observing the patterns formed by X-rays shot through a crystal of the substance. The patterns give important information about the structure of the molecule of interest. In Wilkins’ lab, researcher Rosalind Franklin was using X-ray crystallography to understand the structure of DNA. Watson and Crick were able to piece together the puzzle of the DNA molecule using Franklin's data ( Figure 9.2 ). Watson and Crick also had key pieces of information available from other researchers such as Chargaff’s rules. Chargaff had shown that of the four kinds of monomers (nucleotides) present in a DNA molecule, two types were always present in equal amounts and the remaining two types were also always present in equal amounts. This meant they were always paired in some way. In 1962, James Watson, Francis Crick, and Maurice Wilkins were awarded the Nobel Prize in Medicine for their work in determining the structure of DNA.

Now let’s consider the structure of the two types of nucleic acids, deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). The building blocks of DNA are nucleotides, which are made up of three parts: a deoxyribose (5-carbon sugar), a phosphate group , and a nitrogenous base ( Figure 9.3 ). There are four types of nitrogenous bases in DNA. Adenine (A) and guanine (G) are double-ringed purines, and cytosine (C) and thymine (T) are smaller, single-ringed pyrimidines. The nucleotide is named according to the nitrogenous base it contains.

The phosphate group of one nucleotide bonds covalently with the sugar molecule of the next nucleotide, and so on, forming a long polymer of nucleotide monomers. The sugar–phosphate groups line up in a “backbone” for each single strand of DNA, and the nucleotide bases stick out from this backbone. The carbon atoms of the five-carbon sugar are numbered clockwise from the oxygen as 1', 2', 3', 4', and 5' (1' is read as “one prime”). The phosphate group is attached to the 5' carbon of one nucleotide and the 3' carbon of the next nucleotide. In its natural state, each DNA molecule is actually composed of two single strands held together along their length with hydrogen bonds between the bases.

Watson and Crick proposed that the DNA is made up of two strands that are twisted around each other to form a right-handed helix, called a double helix . Base-pairing takes place between a purine and pyrimidine: namely, A pairs with T, and G pairs with C. In other words, adenine and thymine are complementary base pairs, and cytosine and guanine are also complementary base pairs. This is the basis for Chargaff’s rule; because of their complementarity, there is as much adenine as thymine in a DNA molecule and as much guanine as cytosine. Adenine and thymine are connected by two hydrogen bonds, and cytosine and guanine are connected by three hydrogen bonds. The two strands are anti-parallel in nature; that is, one strand will have the 3' carbon of the sugar in the “upward” position, whereas the other strand will have the 5' carbon in the upward position. The diameter of the DNA double helix is uniform throughout because a purine (two rings) always pairs with a pyrimidine (one ring) and their combined lengths are always equal. ( Figure 9.4 ).

The Structure of RNA

There is a second nucleic acid in all cells called ribonucleic acid, or RNA. Like DNA, RNA is a polymer of nucleotides. Each of the nucleotides in RNA is made up of a nitrogenous base, a five-carbon sugar, and a phosphate group. In the case of RNA, the five-carbon sugar is ribose, not deoxyribose. Ribose has a hydroxyl group at the 2' carbon, unlike deoxyribose, which has only a hydrogen atom ( Figure 9.5 ).

RNA nucleotides contain the nitrogenous bases adenine, cytosine, and guanine. However, they do not contain thymine, which is instead replaced by uracil, symbolized by a “U.” RNA exists as a single-stranded molecule rather than a double-stranded helix. Molecular biologists have named several kinds of RNA on the basis of their function. These include messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA)—molecules that are involved in the production of proteins from the DNA code.

How DNA Is Arranged in the Cell

DNA is a working molecule; it must be replicated when a cell is ready to divide, and it must be “read” to produce the molecules, such as proteins, to carry out the functions of the cell. For this reason, the DNA is protected and packaged in very specific ways. In addition, DNA molecules can be very long. Stretched end-to-end, the DNA molecules in a single human cell would come to a length of about 2 meters. Thus, the DNA for a cell must be packaged in a very ordered way to fit and function within a structure (the cell) that is not visible to the naked eye. The chromosomes of prokaryotes are much simpler than those of eukaryotes in many of their features ( Figure 9.6 ). Most prokaryotes contain a single, circular chromosome that is found in an area in the cytoplasm called the nucleoid.

The size of the genome in one of the most well-studied prokaryotes, Escherichia coli, is 4.6 million base pairs, which would extend a distance of about 1.6 mm if stretched out. So how does this fit inside a small bacterial cell? The DNA is twisted beyond the double helix in what is known as supercoiling. Some proteins are known to be involved in the supercoiling; other proteins and enzymes help in maintaining the supercoiled structure.

Eukaryotes, whose chromosomes each consist of a linear DNA molecule, employ a different type of packing strategy to fit their DNA inside the nucleus ( Figure 9.7 ). Before the structure of DNA was even uncovered, Marie Maynard Daly and Arthur E. Mirsky conducted extensive research in the 1940s and 1950s to understand the molecules and structures in involved. At the most basic level, DNA is wrapped around proteins known as histones to form structures called nucleosomes. The DNA is wrapped tightly around the histone core. This nucleosome is linked to the next one by a short strand of DNA that is free of histones. This is also known as the “beads on a string” structure; the nucleosomes are the “beads” and the short lengths of DNA between them are the “string.” The nucleosomes, with their DNA coiled around them, stack compactly onto each other to form a 30-nm–wide fiber. This fiber is further coiled into a thicker and more compact structure. At the metaphase stage of mitosis, when the chromosomes are lined up in the center of the cell, the chromosomes are at their most compacted. They are approximately 700 nm in width, and are found in association with scaffold proteins.

In interphase, the phase of the cell cycle between mitoses at which the chromosomes are decondensed, eukaryotic chromosomes have two distinct regions that can be distinguished by staining. There is a tightly packaged region that stains darkly, and a less dense region. The darkly staining regions usually contain genes that are not active, and are found in the regions of the centromere and telomeres. The lightly staining regions usually contain genes that are active, with DNA packaged around nucleosomes but not further compacted.

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biotechnology?

DNA is a complex, long-chained molecule that contains the genetic blueprint for building and maintaining all living organisms. Found in nearly all cells, DNA carries the instructions needed to create proteins, specific molecules essential to the development and functioning of the body. It also transfers hereditary information between generations.

This vial contains some of the first DNA Friedrich Miescher isolated from salmon sperm. It is in the possession of the University of Turbingen, Germany. Credit: Alfons Renz.

DNA is central to biotechnology and medicine by virtue of the fact that it not only provides the basic blueprint for all life, it is a fundamental determinant of how the body functions and the disease process. Understanding the structure and function of DNA has helped revolutionise the investigation of disease pathways, assess an individual’s genetic susceptibility to specific diseases, diagnose genetic disorders, and formulate new drugs. It is also critical to the identification of pathogens. Aside from its medical uses, the fact that DNA is unique to each individual makes it a vital forensic tool identifying criminals, the remains of a missing person, and determining the biological parent of a child. Within agriculture DNA is also used to help improve animal livestock and plants.

The discovery of DNA stretches back to 1869, when Friedrich Miescher, a Swiss physician and biologist, began examining leucocytes, a type of white blood cell, he had sourced from pus collected on fresh surgical bandages. This he did while working in the laboratory of Felix Hoppe-Seyler in Tubingen, Germany as part of project to determine the chemical building blocks of cells. On looking through the microscope he observed that a substance separated from the solution of the cells whenever he added an acid and then dissolved again once alkali was added. The compound bore no resemblance to any known protein. Believing the substance to originate from the nuceli of the cell, Miescher nicknamed it 'nuclein'. On investigating further he discovered nuclein to be present in many other tissues. While possessing only simple tools and methods, by 1874 Miescher had come close to working out the genetic role of nuclein. He lacked sufficient communication skills, however, to convey the importance of what he had found to the wider scientific world. In 1881 Albrecht Kossel, a German biochemist, renamed Miescher's compound deoxyribonucleic acid (DNA) based on the fact that he had discovered it to be a nucleic acid. Following this, he began working out its chemical composition. By 1901 he determined it to be made up of five nitrogen bases: adenine (A), cytosine (C), guanine (G), thymine (T) and uracil (U). For many decades DNA remained little studied because it was assumed to be an inert substance incapable of carrying genetic material because of its simple structure. Proteins were instead thought to be the carriers of genetic material. In part this was because they had a more complex structure, being made up of 20 different amino acids. It would not be until the mid 20th century that attitudes towards DNA began to change. This was prompted by the work of Oswald Avery at Rockefeller Institute in New York. From the early 1930s, Avery began to investigate how a type of non-infectious bacteria associated with pneumonia could transform into dangerous virulent forms if mixed with dead cells from the virulent strain and carried this trait into their offspring. The phenomenon had been first observed by Fred Griffith, a British physician, in 1928. By 1944 Avery had demonstrated with the help of his colleagues Colin MacLeod and Maclyn McCarty, that the transformation of the bacteria was linked to a stringy white substance – DNA. While not universally accepted at the time, Avery's finding helped kindle a new interest in DNA. It would take another few years before scientists finally accepted that it was DNA, not proteins, that carried DNA. It was finally agreed following experiments conducted by Alfred Hershey and Martha Hershey at Cold Spring Harbor in 1952. By the 1950s a number of researchers had begun to investigate the structure of DNA in the hope that this would reveal how the molecule worked. Its structure was finally unveiled in 1953 through the combined efforts of the biophysicists Rosalind Franklin and Maurice Wilkins, based at King's College London, and Francis Crick and James Watson based in the Cavendish Laboratory, Cambridge University. Their work determined DNA to be a long linear molecule made up of two strands coiled around each other in a spiral configuration later known as the 'double helix'. Each strand was made up of four complementary nucleotides, chemical subunits: adenine (A), cytosine (C), guanine (G) and thymine (T). The two strands were oriented in opposite directions so that adenine always joined thymines (A T) and cytosines were linked with guanines (C G). Watson and Crick argued this structure helped each strand to reconstruct the other and facilitate the passing on of hereditary information.

Application

The analysis of DNA is pivotal to understanding both the biological mechanisms of life and diseases that arise when this process goes wrong. Many different applications have been developed to understand this process. Today scientists can analyse the molecule through a range of techniques, including DNA sequencing which helps work out its structure, through to PCR, which rapidly amplifies tiny quantities of DNA into billions of copies. Such techniques underpin all tests carried out today to for example identify a genetic mutation that causes cancer, or to determine whether a person carries a gene for a hereditary disease that can be passed on to their offspring. In addition, scientists have found ways to manipulate and construct new forms of DNA, known as recombinant DNA or gene cloning. Such technology is crucial to the mass production of many drugs, such as interferon, and the development of gene therapy.

DNA: timeline of key events

First observation of chromosomes by Swiss botanist Karl von Nageli

13 Aug 1844

Johann Friedrich Miescher was born in Basel, Switzerland

Edouard van Beneden was born in Leuven, Belgian

1864 - 1865

Nucleus shown to contain genetic substance

Discovery of DNA

25 Feb 1869

Phoebus Levene was born in Sagor, Russia (now Zagare, Lithuania)

1877 - 1880

Nucleic acid shown to have protein and non-protein components

21 Oct 1877

Oswald T Avery was born in Halifax, Canada

Chromosomes and the process of mitiotic cell division first discovered

Chromosome first discovered

1885 - 1901

Nucleic acids structure determined

Richard Altmann, German pathologist, renames nuclein as nucleic acid

26 Aug 1895

Johann Friedrich Miescher died

A nucelotide called tuberculinic acid found to bind to the protein tuberculin. It is now regarded as the precursor to the discovery of DNA methylation

28 Feb 1901

Linus C Pauling was born in Portland OR, USA

Chromosomes linked with inheritance

The notion genetics is introduced

24 Sep 1905

Severo Ochoa was born in Luarca, Spain

Alexander R Todd was born in Glasgow, Scotland

The term gene is first used

First description of the building blocks of DNA

28 Apr 1910

Edouard van Beneden died

22 Nov 1912

Paul Zamecnik was born in Cleveland, Ohio, USA

First mapping of a chromosome

14 Dec 1914

Solomon Spiegelman was born in Brooklyn, NY, USA

Francis H C Crick was born in Northampton, UK

15 Dec 1916

Maurice H F Wilkins was born in Pongaroa, New Zealand

Arthur Kornberg was born in Brooklyn NY, USA

13 Aug 1918

Frederick Sanger, twice Nobel Prize winner, born

25 Jul 1920

Rosalind E Franklin was born in London, UK

Evelyn Witkin was born in New York City, USA

15 Oct 1921

Seymour Benzer was born in Brooklyn, NY, USA

Har Gobind Khorana was born in Raipur, India

John D Smith was born in Southampton, UK

23 May 1925

Joshua Lederberg was born in Montclair, NJ, USA

T.B. Johnson and R.D. Coghill reported detecting a minor amount of methylated cytosine derivative as byproduct of hyrdrolysis of tuberculinic acid with sulfuric acid but other scientists struggled to replicate their results.

30 Jun 1926

Paul Berg was born in New York NY, USA

10 Apr 1927

Marshall W Nirenberg was born in New York NY, USA

Bacteria shown capable of transformation

James D Watson was born in Chicago, IL, USA

14 Aug 1928

Ray Wu was born in Beijing, China

30 Oct 1928

Daniel Nathans was born in Wilmington, Delaware, USA

Werner Arber was born in Granichen, Switzerland

Franklin W Stahl was born in Boston, Massachusetts, USA

23 Jan 1930

Beverly Griffin was born in Delhi, Louisiana, USA

Barbara McClintock and Harriet Creighton, her graduate student, provided first experimental proof that genes are positioned on chromosomes

23 Aug 1931

Hamilton O Smith was born in New York City, USA

Sanger attends Bryanston School, Dorset, as boarder

21 Mar 1932

Walter Gilbert was born in Boston MA, USA

30 Jun 1935

Stanley Norman Cohen was born in Perth Amboy, NJ, USA

1936 - 1940

Sanger takes degree in Natural Sciences at Cambridge University

10 Jul 1936

Herbert Boyer was born in Derry, Pennsylvania, USA

David Baltimore was born in New York City

1940 - 1943

Sanger studies for a doctorate at Cambridge University

Phoebus Levene died

Term 'genetic engineering' first coined

27 Mar 1942

John E Sulston born in Cambridge, UK

26 Feb 1943

Erwin Schrodinger proposed that life was passed on from generation to generation in a molecular code.

15 May 1943

Oswald claimed DNA to be the 'transforming factor' and the material of genes

Richard J Roberts was born in Derby, United Kingdom

Sanger starts working on amino acid composition of insulin

Evelyn Witkin discovered radiation resistance in bactiera

DNA identified as a hereditary agent

14 Oct 1946

J Craig Venter was born in Salt Lake City, Utah

29 Nov 1947

Robert Swanson was born in Florida, USA

DNA content of a cells linked to a cell's number of chromosomes

1949 - 1950

DNA four base ratio shown to be always consistent

Sickle cell shown to be caused by genetic mutation

Esther Lederberg discovered the lambda phage

Purified DNA and DNA in cells shown to have helical structure

First observation of the modification of viruses by bacteria

28 Sep 1952

Experiments proved DNA, and not proteins, hold the genetic code

Nature published Crick and Watson's letter on Molecular Structure of Nucleic Acids

25 Apr 1953

Nature published three papers showing the molecular structure of DNA to be a double helix

31 Oct 1954

Linus Pauling was awarded the Nobel Prize

Sanger completes the full sequence of amino acids in insulin

Oswald T Avery died

15 Oct 1955

Virus dismantled and put back together to reconstitute a live virus

Transfer RNA (tRNA) discovered

First observation of messenger RNA, or mRNA

16 Apr 1956

DNA polymerase isolated and purified and shown to replicate DNA

Victor Ingram breaks the genetic code behind sickle-cell anaemia using Sanger's sequencing technique

19 Sep 1957

Francis Crick presented the theory that the main function of genetic material is to control the synthesis of proteins

First synthesis of DNA in a test tube

Sanger awarded his first Nobel Prize in Chemistry

16 Apr 1958

Rosalind E Franklin died

15 Jul 1958

DNA replication explained

16 Mar 1959

Existence of gene regulation established

Steps in protein synthesis outlined

New technique published for mapping the gene shows genes are linear and cannot be divided

National Biomedical Research Foundation established

Sanger begins to devise ways to sequence nucleic acids, starting with RNA

1961 - 1966

Genetic code cracked for the first time

'Jumping genes', transposable elements, discovered by Barbara McClintock

13 May 1961

Experiment confirms existence of mRNA

15 May 1961

Coding mechanism for DNA cracked

Sanger moves to the newly created Laboratory of Molecular Biology in Cambridge

23 Jan 1962

Idea of restriction and modification enzymes born

18 Oct 1962

Nobel Prize for Physiology or Medicine awarded for determining the structure of DNA

19 Oct 1962

Nobel Prize awarded for uncovering the structure of DNA

Evelyn Witkin discovered that UV mutagenesis in E. coli could be reversed through dark exposure

Transfer RNA is the first nucleic acid molecule to be sequenced

First comprehensive protein sequence and structure computer data published as 'Atlas of Protein Sequence and Structure'

Ledley publishes Uses of Computers in Biology and Medicine

Sanger and colleagues publish two-dimension partition sequencing method

18 Jan 1965

First summary of the genetic code was completed

Werner Arber predicted restriction enzymes could be used as a labortory tool to cleave DNA

Discovery ligase, an enzyme that facilitates the joining of DNA strands

First automatic protein sequencer developed

Chromosome with a specific gene isolated from hybrid cells produced from fused mouse and human cells

14 Dec 1967

Functional, 5,000-nucleotide-long bacteriophage genome assembled

The first partial sequence of a viral DNA is reported

Paul Berg started experiments to generate recombinant DNA molecules

First principles for PCR published

New species of bacterium is isolated from hot spring in Yellowstone National Park by Thomas Brock

New idea for generating recombinant DNA conceived

Discovery of methylase, an enzyme, found to add protective methyl groups to DNA

First complete gene synthesised

First method published for staining human or other mammalian chromosomes

First restriction enzyme isolated and characterised

27 Jul 1970

Reverse transcriptase first isolated

Mertz started her doctorate in biochemistry at Stanford University under Paul Berg

Process called repair replication for synthesising short DNA duplexes and single-stranded DNA by polymerases is published

First plasmid bacterial cloning vector constructed

Complete sequence of bacteriophage lambda DNA reported

Janet Mertz forced to halt experiment to clone recombinant DNA in bacteria after safety concerns raised

First experiments published demonstrating the use of restriction enzymes to cut DNA

26 Sep 1972 - 4 Sep 1972

First time possible biohazards of recombinant DNA technology publicly discussed

First recombinant DNA generated

Janet Mertz and Ronald Davis published first easy-to-use technique for constructing recombinant DNA showed that when DNA is cleaved with EcoRI, a restriction enzyme, it has sticky ends

The sequencing of 24 basepairs is reported

1973 - 1976

Discovery of DNA repair mechanism in bacteria - the SOS response

Ames test developed that identifies chemicals that damage DNA

10 Jun 1973 - 13 Jun 1973

First international workshop on human gene mapping held

First time DNA was successfully transferred from one life form to another

Regulation begins for recombinant genetic research

Recombinant DNA successfuly reproduced in Escherichia coli

Temporary moratorium called for on genetic engineering until measures taken to deal with potential biohazards

Mertz completed her doctorate

Sanger and Coulson publish their plus minus method for DNA sequencing

DNA methylation suggested as mechanism behind X-chomosome silencing in embryos

DNA methylation proposed as important mechanism for the control of gene expression in higher organisms

Asilomar Conference called for voluntary moratorium on genetic engineering research

Yeast genes expressed in E. coli bacteria for the first time

11 Mar 1976

Proto-oncogenes suggested to be part of the genetic machinery of normal cells and play important function in the developing cell

Genentech founded

23 Jun 1976

NIH released first guidelines for recombinant DNA experimentation

Human growth hormone genetically engineered

Complete sequence of bacteriophage phi X174 DNA determined

First computer programme written to help with the compilation and analysis of DNA sequence data

Two different DNA sequencing methods published that allow for the rapid sequencing of long stretches of DNA

Human insulin produced in E-coli

Nobel Prize given in recognition of discovery of restriction enzymes and their application to the problems of molecular genetics

Biogen filed preliminary UK patent for technique to clone hepatitis B DNA and antigens

First DNA fragments of Epstein Barr Virus cloned

University of Edinburgh scientists published the successful isolation and cloning DNA fragments of the hepatitis B virus in Escherichia coli

May 1979 - Oct 1979

Pasteur Institute scientists reported successful cloning of hepatitis B DNA in Escherichia coli

30 Aug 1979

UCSF scientists announced the successful cloning and expression of HBsAg in Escherichia coli

21 Dec 1979

Biogen applied for European patent to clone fragment of DNA displaying hepatitis B antigen specificity

Genetic engineering recognised for patenting

First patent awarded for gene cloning

Cesar Milstein proposed the use of recombinant DNA to improve monoclonal antibodies

Sanger awarded his second Nobel Prize in Chemistry

European Molecular Biology Laboratory convenes meeting on Computing and DNA Sequences

Polyoma virus DNA sequenced

31 Jul 1980

UCSF scientists published method to culture HBsAg antigens in cancer cells

Scientists reported the first successful development of transgenic mice

15 Sep 1980

Largest nucleic acid sequence database in the world made available free over telephone network

First genetically-engineered plant reported

First genetically cloned mice

First evidence provided to show that DNA methylation involved in silencing X-chromosome

UCSF and Merck filed patent to snthesise HBsAg in recombinant yeast

10 Jul 1981

Complete library of overlapping DNA fragments of Epstein Barr Virus cloned

Whole genome sequencing method is introduced for DNA sequencing

1982 - 1985

Studies reveal azacitidine, a cytoxic agent developed by Upjohn, inhibits DNA methylation

NIH agrees to provide US$3.2 million over 5 years to establish and maintain a nucleic sequence database

First recombinant DNA based drug approved

Sanger retires

Widespread loss of DNA methylation found on cytosine-guanine (CpG) islands in tumour samples

20 Jan 1983

Solomon Spiegelman died

Polymerase chain reaction (PCR) starts to be developed as a technique to amplify DNA

Results from PCR experiments start being reported

Genetically engineered vaccine against hepatitis B reported to have positive trial results

10 Sep 1984

First genetic fingerprint revealed

First chimeric monoclonal antibodies developed, laying foundation for safer and more effective monoclonal antibody therapeutics

Carol Greider and Elizabeth Blackburn announced the discovery of telomerase, an enzyme that adds extra DNA bases to the ends of chromosomes

DNA methylation found to occur on specific DNA segments called CpG islands

Mullis and Cetus Corporation filed patent for the PCR technique

DNA fingerprinting principle laid out

17 May 1985

1st legal case resolved using DNA fingerprinting

20 Dec 1985

The Polymerase Chain Reaction (PCR) technique was published

First machine developed for automating DNA sequencing

Plans for sequencing human genome first laid out

First humanised monoclonal antibody created

First genetically engineered vaccine against hepatitis B approved

Interferon approved for treating hairy cell leukaemia

26 Jun 1986

US regulatory framework established to regulate development and introduction of biotechnology products

Genetically engineered hepatitis B vaccine, Engerix-B, approved in Belgium

18 Dec 1986

Results released from first small-scale clinical trial of recombinant interferon-alpha therapy for post-transfusion chronic hepatitis B

mRNA encapsulated into liposome made with cationic lipids injected into mouse cells shown to produce proteins

Campath-1H is created - the first clinically useful humanised monoclonal antibody.

US Congress funds genome sequencing

Development of first rapid search computer programme to identify genes in a new sequence

12 Apr 1988

OncoMouse patent granted

20 Oct 1988

Cloning of first mammalian enzyme (DNA methyltransferase, DNMT) that catalyses transfer of methyl group to DNA

Genetically engineered hepatitis B vaccine, Engerix-B, approved in US

Genetically engineered hepatitis B vaccine, GenHevac, approved in France

25 May 1989

David Deamer draws the first sketch to use a biological pore to sequence DNA

DNA methylation suggested to inactivate tumour suppressor genes

First pitch for US Human Genome Project

Human Genome Project formally launched

BRCA1, a single gene on chromosome 17, shown to be responsible for many breast and ovarian cancers

21 Dec 1990

BRCA1 gene linked with inherited predisposition to cancer

GenBank is integrated into the NIH National Center for Biotechnology Information

Method devised to isolate methylated cytosine residues in individual DNA strands providing avenue to undertake DNA methylation genomic sequencing

13 Jul 1992

FDA approved the use of genetically engineered interferon-alpha, Intron A, for the treatment of hepatitis B

First experimental evidence showing links between diet and DNA methylation and its relationship with cancer

13 Oct 1993

Cetus Corporation was sold to Chiron and its patent rights sold for US$300 million to Hoffman-La Roche

Severo Ochoa died

30 Dec 1993

FDA appproved genetically engineered enzyme drug for cystic fibrosis

19 Aug 1994

Linus C Pauling died

22 Dec 1994

First chimeric monoclonal antibody therapeutic approved for market

21 Apr 1995

First evidence published to demonstrate reduced DNA methylation contributes to formation of tumours

28 Jul 1995

First complete genome sequence published for a self-replicating free-living organism

Complete genome sequence of the first eukaryotic organism, the yeast S. cerevisiae, is published

Pyrosequencing is introduced for DNA sequencing

10 Jan 1997

Alexander R Todd died

First humanised monoclonal antibody approved for market

Commercial Human Genome Project launched

11 Jun 1998

Complete genome sequence of bacteria that causes tuberculosis published

17 Jul 1998

Genome map published for Treponema pallidum, bacteria that causes syphilis

11 Dec 1998

Publication of complete genome sequence of the nematode worm Caenorhabditis elegans

First human chromosome sequence published

20 Jul 1999

DNA methylation of CpG islands shown to be linked to colorectal cancer

16 Nov 1999

Daniel Nathans died

Term 'nanopore' used for first time in a publication

Robert Swanson died

Complete sequences of the genomes of the fruit fly Drosophila and the first plant, Arabidopsis, are published

26 Jun 2000

Human genome draft sequence announced

14 Dec 2000

First complete plant genome sequenced

First consensus sequence of human genome published

Complete genome sequence of the first mammalian model organism, the mouse, is published

12 Jul 2002

Polio: First ever virus synthesised from chemicals alone

Genomic sequence of the principal malaria parasite and vector completed

The sequence of the first human genome was published

22 Nov 2003

John D Smith died

FDA approved first DNA methylation inhibitor drug, azacitidine (Vidaza®), for treatment of rare bone marrow disorder

28 Jul 2004

Francis Crick died.

Maurice H F Wilkins died

23 Dec 2004

FDA approved first DNA microarray diagnostic device

Enzyme Ubp10 demonstrated to protect the genome from potential destabilising molecular events

Oxford Nanopore Technology secured two rounds of seed funding from IP Group Plc

FDA approved second DNA methylation inhibitior, decatabine (Dacogen)

Last human chromosome is sequenced

2007 - 2016

Human Microbiome Project (HMP) carried out

Oxford Nanopore Technology decides to focus its resources on developing nanopore sequencing for DNA sequencing

26 Oct 2007

Arthur Kornberg died

30 Nov 2007

Seymour Benzer died

Structure of telomerase, an enzyme that conserves the ends of chomosomes, was decoded

2008 - 2012

METAgenomics of the Human Intestinal Tract (MetaHIT) project carried out

Joshua Lederberg died

10 Feb 2008

Ray Wu died in Ithaca, USA

27 Dec 2009

Paul Zamecnik died

DNA sequencing proves useful to documenting the rapid evolution of Streptococcus pneumococci in response to the application of vaccines

Hand-held DNA sequencer (MinION) successfully used to sequence first piece of DNA

Har Gobind Khorana died

15 Feb 2012 - 18 Feb 2012

MinION presented in public for first time

DNA sequencing helps identify the source of an MRSA outbreak in a neornatal intensive care unit

DNA sequencing utilised for identifying neurological disease conditions different from those given in the original diagnosis

19 Nov 2013

Fred Sanger, the inventor of DNA sequencing, died at the age of 95

Promising results announced from trial conducted with HIV patients

Oxford Nanopore Technology released its palm-sized DNA sequencer to researchers through its MinION Access Programme

Nobel Prize in Chemistry was awarded to scientists for understanding the process of DNA repair

13 Jun 2016

Beverly Griffin died

Research showed simple blood test can identify patients at most risk of skin cancer returning

15 Nov 2017

Rare mutation of gene called Serpine 1 discovered to protect against biological ageing process

29 Jan 2018

MinION shown to be promising tool for sequencing human genome

John E Sulson died

12 Jul 2018

Genetic test shown to accurately predict which women benefit from chemotherapy

Genomics England completed sequencing 100,000 whole genomes

NHS introduced new fast-track DNA test to scan for rare diseases in babies and children

15 Feb 2023

Paul Berg died

Science links: Science home | Cancer immunotherapy | CRISPR-Cas9 | DNA extraction | DNA polymerase | DNA Sequencing | Epigenetics | Faecal microbiota transplant | Gene therapy | Immune checkpoint inhibitors | Infectious diseases | Messenger RNA (mRNA) | Monoclonal antibodies | Nanopore sequencing | Organ-on-a-chip | p53 Gene | PCR | Phage display | Phage therapy | Plasmid | Recombinant DNA | Restriction enzymes | Stem cells | The human microbiome | Transgenic animals |

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Unit 15: DNA as the genetic material

About this unit.

This unit is part of the Biology library. Browse videos, articles, and exercises by topic.

Structure of DNA

• DNA (Opens a modal)
• Molecular structure of DNA (Opens a modal)
• Antiparallel structure of DNA strands (Opens a modal)
• Nucleic acids (Opens a modal)
• Nucleic acids Get 3 of 4 questions to level up!

Discovery of DNA

• DNA as the "transforming principle" (Opens a modal)
• Hershey and Chase: DNA is the genetic material (Opens a modal)
• Classic experiments: DNA as the genetic material (Opens a modal)
• The discovery of the double helix structure of DNA (Opens a modal)
• Discovery of the structure of DNA (Opens a modal)
• Discovery of DNA Get 3 of 4 questions to level up!

DNA replication

• DNA replication and RNA transcription and translation (Opens a modal)
• Leading and lagging strands in DNA replication (Opens a modal)
• Speed and precision of DNA replication (Opens a modal)
• Molecular mechanism of DNA replication (Opens a modal)
• Mode of DNA replication: Meselson-Stahl experiment (Opens a modal)
• DNA proofreading and repair (Opens a modal)
• Telomeres and telomerase (Opens a modal)
• DNA replication Get 3 of 4 questions to level up!

Realizing the benefits of human genetics and genomics research for people everywhere.

2022 DNA Day Essay Contest: Full Essays

1 st  Place : Man Tak Mindy Shie, Grade 12 Teacher:  Dr. Siew Hwey Alice Tan School:  Singapore International School (Hong Kong) Location:  Hong Kong, China

Many would say that the most significant stride in recent genetics has been the completion of the human genome, which laid the basis for studying genetic variation. However, let us not forget that this began with the understanding of heredity based on Gregor Mendel’s observations in 1857.

Observations from Mendel’s pea plant hybridization experiments led to two fundamental principles of inheritance (1). The first was the Law of Segregation, which states that reproductive gamete cells transmit only one allele to their offspring. This means that a diploid offspring will inherit one allele from each parent. We now understand genes to be the units of heredity that carry genetic information and alleles to be different variants of a gene (2). Mendel’s second principle, the Law of Independent Assortment, states that alleles are assorted independent of each other during gamete formation, leading to individual traits being inherited independently (1). Additionally, Mendel discovered that alleles could either be dominant or recessive. An allele that constituted a phenotypic trait over the other in a heterozygous genotype was labeled dominant, while the other phenotypically unexpressed allele was called recessive (3). A class of diseases was subsequently named after Mendel as they follow the same observations; Mendelian disorders are inherited monogenic diseases that result from mutation at a single gene locus (4). A notable example is phenylketonuria, where loss-of-function mutations in the PAH gene cause systemic excess phenylalanine, resulting in behavioral abnormalities (5).

Mendel’s Laws still provide important insight in understanding Mendelian traits. For example, the Law of Segregation created the basis of dominant and recessive phenotypic ratios (6). The phenotypic ratios in family pedigrees thus allow inference of dominant and recessive traits. This is additionally helpful when an unknown disorder is found to be a Mendelian trait. Since Mendelian traits have complete penetrance, i.e. individuals carrying the pathogenic variant always express the associated trait, it is possible to search for the gene-of-interest when parental genomes are also sequenced. In present-day analysis, Whole Exome Sequencing leverages the fact that most complete penetrance genes lie in the coding region of the genome; this reduces cost and search space for identifying novel diseases (7).

We now know that the Law of Independent Assortment is applicable only when traits are located on different chromosomes. Therefore, it is important in laying the assumption of the lack of linkage between different traits whose loci are genetically far apart. Traditionally, linkage analysis used this prerequisite to identify specific loci within the disease-causing organism, as genes in proximity are often in linkage and do not sort independently (7). Regardless, this stipulation could lead to the belief that the Law of Independent Assortment has less direct value in understanding Mendelian disorders.

In contrast to monogenic diseases, complex diseases arise from multiple genetic and/or environmental factors, displaying complicated inheritance and genetics (1,8). Asthma, for example, was shown to be associated with more than 100 genes with significant inter-population variation (9), and is clinically associated with environmental allergens. Researchers are still looking for contributing variants of many common complex diseases as, unlike Mendelian Disorders, the additive inheritance explained by the associated variants does not explain the genetic contribution to the disease determined by twin studies (8). This is known as the ‘missing heritability problem’, and has prompted scientists to look for other clues.

One way to unravel complex disease genetics lies in the functional characterization of gene variants. Mendelian Diseases thus became an important way to study the link between the genotype-phenotype relationship due to a clear causal relationship and complete penetrance. This puts us in a better position to understand why a variant results in a phenotypic trait (6). Moreover, Mendelian traits allow us to elucidate the functional perturbation due to the mutation itself, providing an excellent opportunity to understand how a change in RNA/protein function caused by mutations can contribute to pathogenesis (6). When variants within complex traits, whether rare or common, are involved within neighboring variants of Mendelian traits, molecular insight may be provided regarding the pathways involved in pathogenesis. Therefore, studying the molecular basis of Mendelian traits could provide essential clues to the bigger puzzle of complex disease.

In the late 2000s, Genome-Wide Associated Studies focused on complex traits and forced Mendelian Diseases to take a back seat; yet today we find that many genetic variants must first be understood through studying Mendelian Diseases. While most Mendelian Diseases are low in incidence, they nonetheless provide valuable lessons as we continue on our journey to understand human genetics.

Citations/References:

• Kennedy, M.A. (2005). Mendelian Genetic Disorders. In eLS, (Ed.). https://doi.org/10.1038/npg.els.0003934
• Cooper, G. M. (2000). The Cell: A Molecular Approach. 2nd edition. NCBI. Retrieved 2022, from https://www.ncbi.nlm.nih.gov/books/NBK9944/
• Wanjin, X., & Morigen, M. (2015). Understanding the cellular and molecular mechanisms of dominant and recessive inheritance in genetics course. Yi chuan = Hereditas, 37(1), 98–108. https://doi.org/10.16288/j.yczz.2015.01.014
• Prosen, T., & Hogge, W. (2008). Molecular and Mendelian Disorders. The Global Library of Women’s Medicine. https://www.glowm.com/section-view/heading/Molecular%20and%20Mendelian%20Disorders/item/223#.YhygEJNBzAN
• MedlinePlus. (2021). Phenylketonuria. https://medlineplus.gov/genetics/condition/phenylketonuria/
• Mendel, G., & Bateson, W. (2013). Mendel’s Principles of Heredity Dover Books on Biology. Courier Corporation.
• Antonarakis, S. E., Chakravarti, A., Cohen, J. C., & Hardy, J. (2010). Mendelian disorders and multifactorial traits: the big divide or one for all?. Nature reviews. Genetics, 11(5), 380–384. https://doi.org/10.1038/nrg2793
• What are complex or multifactorial disorders?: MedlinePlus Genetics. (2021). Medline Plus. https://medlineplus.gov/genetics/understanding/mutationsanddisorders/complexdisorders/
• Allergic asthma: MedlinePlus Genetics. (2020). MedlinePlus. https://medlineplus.gov/genetics/condition/allergic-asthma/

2 nd  Place: Gillian Wells, Grade 11 Teacher:  Mrs. Rebecca Hodgson School:  Ulverston Victoria High School Location:  Ulverston, England, UK

Mendel is often referred to as the “Father of Modern Genetics” (1). Prior to his experiments in plant hybridization, it was believed inherited traits resulted from blending the traits of each parent (2). From his studies, Mendel derived three principles of inheritance: the laws of dominance (in a heterozygote, the dominant allele conceals the presence of the recessive allele), segregation (each individual possesses two alleles for a specific trait, one inherited from each parent, and segregated during meiosis) and independent assortment (alleles for separate traits are inherited independently) (3, 4).

These principles give a pattern of inheritance followed by Mendelian or monogenic disorders – disorders caused by variation in a single gene (5). Mendel’s law of dominance explains the pattern of inheritance for autosomal dominant monogenic disorders, which present in individuals with only one dominant mutated allele (2). The heredity of dominant disorders – for example, Huntington’s disease and myotonic dystrophy – therefore follow the same pattern as the dominant traits Mendel observed in pea plants (4, 6). Mendel’s law of dominance also explains the pattern of inheritance for autosomal recessive monogenic disorders, which are not expressed in heterozygous individuals (carriers) as the dominant allele ‘hides’ the mutated recessive allele. Therefore, in families with multiple affected generations, the disorder will appear to ‘skip’ generations, only presenting in individuals that inherit two recessive mutated alleles of the same gene, one from each parent, as explained by Mendel’s law of segregation (2). The heredity of recessive disorders – for example, phenylketonuria and cystic fibrosis – therefore follow the same pattern as the recessive traits Mendel observed in pea plants (4, 6).

This understanding of inheritance patterns establishes the causal relationship between genes and Mendelian disorders, between genotype and phenotype (7). From this, many Mendelian disorder gene identification approaches have been developed, from positional cloning and linkage mapping to whole exome and genome sequencing (8, 9). The results are compiled in Online Mendelian Inheritance in Man (OMIM), a comprehensive database of human genes and genetic disorders, with over 26,000 entries describing over 16,000 genes and 9,000 Mendelian phenotypes (10, 11). Identifying these causal genes improves understanding of specific Mendelian disorders, allowing for molecular diagnosis and carrier testing (9).

In contrast, complex or polygenic diseases are caused by variation in multiple genes interacting with environmental and lifestyle factors, and so do not follow Mendelian inheritance patterns (12). However, widespread comorbidity between Mendelian disorders and complex diseases has been identified, suggesting a genetic association (14). Recent studies have shown that nearly 20% of the identified genes underlying Mendelian disorders contain variants responsible for genome-wide association study (GWAS) signals that cause complex diseases. 15% of all genes underlie Mendelian disorders. Mendelian genes are therefore enriched in GWAS signals and so contribute to the etiology of corresponding complex diseases (13, 14).

Given that different variants of the same gene can give rise to several different phenotypes, some Mendelian genes carry variants that contribute to complex diseases as well as causal variants for Mendelian disorders (13, 15). For example, the gene ABCA4 causes the monogenic conditions retinitis pigmentosa and Stargardt disease, as well as the complex disease age-related macular degeneration (15). Therefore, selecting genes that cause Mendelian disorders for candidate gene association studies can reveal variants that contribute to the etiology of complex diseases, allowing their genetic basis to be understood (10).

Given this genetic association between Mendelian disorders and complex diseases, the identification of Mendelian genes and knowledge of their expression can be used to further understand the mechanisms of associated complex diseases. An example in cardiovascular disease (CVD) research is the identification of causal genes for the monogenic disorder severe hypercholesterolemia. This has provided invaluable insights into lipid transport, leading to an improved understanding of CVD. From this, successful therapies have been developed for CVD using knowledge of the relevant genes and pathways (16). Mutation mechanisms observed in Mendelian disorders that can provide insight into complex disease include anticipation, gene dosage effects, and uniparental disomy (10).

Overall, Mendel’s discoveries revolutionized genetics, creating a model of inheritance that led to advancements in the diagnosis, treatment, and genetic understanding of inherited Mendelian disorders. In turn, research of Mendelian disorders has provided an understanding of the causes and mechanisms of complex diseases through genetic association – up to 23% of genes known to cause Mendelian disorders have been associated with a complex disease (17). The study of Mendelian phenotypes has and will continue to provide breakthroughs in the development of treatments and therapies of all genetic disorders (10).

References/Citations:

• Dastur, AdiE, and PD Tank. “Gregor Johann Mendel: The Father of Modern Genetics.” Journal of Prenatal Diagnosis and Therapy, vol. 1, no. 1, 2010, p. 3, https://doi.org/10.4103/0976-1756.62132.
•  Reyna, Barbara, and Rita Pickler. “Patterns of Genetic Inheritance.” Neonatal Network, vol. 18, no. 1, Feb. 1999, pp. 7–10, https://doi.org/10.1891/0730-0832.18.1.7.
•  Miko, Ilona. “Gregor Mendel and the Principles of Inheritance | Learn Science at Scitable.” Nature.com, 2014, www.nature.com/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593/#.
• Mendel, Gregor. “Versuche Über Pflanzen-Hybriden.” Der Züchter, vol. 13, no. 10-11, Oct. 1941, pp. 221–68, https://doi.org/10.1007/bf01804628.
• Jensen, Peter K. A. “[Monogenic Hereditary Diseases].” Ugeskrift for Laeger, vol. 165, no. 8, Feb. 2003, pp. 805–9, pubmed.ncbi.nlm.nih.gov/12625123/.
• Chial, Heidi. “Gregor Mendel and Single-Gene Disorders | Learn Science at Scitable.” Nature.com, 2014, www.nature.com/scitable/topicpage/mendelian-genetics-patterns-of-inheritance-and-single-966/.
• Hansen, Adam W., et al. “A Genocentric Approach to Discovery of Mendelian Disorders.” The American Journal of Human Genetics, vol. 105, no. 5, Nov. 2019, pp. 974–86, https://doi.org/10.1016/j.ajhg.2019.09.027.
•  Botstein, David, and Neil Risch. “Discovering Genotypes Underlying Human Phenotypes: Past Successes for Mendelian Disease, Future Approaches for Complex Disease.” Nature Genetics, vol. 33, no. S3, Mar. 2003, pp. 228–37, https://doi.org/10.1038/ng1090.
• Gilissen, Christian, et al. “Unlocking Mendelian Disease Using Exome Sequencing.” Genome Biology, vol. 12, no. 9, 2011, p. 228, https://doi.org/10.1186/gb-2011-12-9-228.
• Antonarakis, Stylianos E., and Jacques S. Beckmann. “Mendelian Disorders Deserve More Attention.” Nature Reviews Genetics, vol. 7, no. 4, Mar. 2006, pp. 277–82, https://doi.org/10.1038/nrg1826.
• Hamosh, Ada. “OMIM Entry Statistics.” Omim.org, omim.org/statistics/entry#.
• SCHORK, NICHOLAS J. “Genetics of Complex Disease.” American Journal of Respiratory and Critical Care Medicine, vol. 156, no. 4, Oct. 1997, pp. S103–9, https://doi.org/10.1164/ajrccm.156.4.12-tac-5.
• Blair, David R., et al. “A Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk.” Cell, vol. 155, no. 1, Sept. 2013, pp. 70–80, https://doi.org/10.1016/j.cell.2013.08.030.
• Chong, Jessica X., et al. “The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities.” The American Journal of Human Genetics, vol. 97, no. 2, Aug. 2015, pp. 199–215, https://doi.org/10.1016/j.ajhg.2015.06.009.
• Dean, Michael. “Approaches to Identify Genes for Complex Human Diseases: Lessons from Mendelian Disorders.” Human Mutation, vol. 22, no. 4, Aug. 2003, pp. 261–74, https://doi.org/10.1002/humu.10259.
• Kathiresan, Sekar, and Deepak Srivastava. “Genetics of Human Cardiovascular Disease.” Cell, vol. 148, no. 6, Mar. 2012, pp. 1242–57, https://doi.org/10.1016/j.cell.2012.03.001.
• Spataro, Nino, et al. “Properties of Human Disease Genes and the Role of Genes Linked to Mendelian Disorders in Complex Disease Aetiology.” Human Molecular Genetics, vol. 26, no. 3, Feb. 2017, pp. 489–500, https://doi.org/10.1093/hmg/ddw405.

3 rd  Place:  Yiyang Zhang, Grade 11 Teacher:  Dr. Qiongyu Zeng School:  Shanghai High School International Division Location:  Shanghai, China

Natural populations are characterized by astonishing phenotypic diversity determined by genes and dynamic environmental factors. In 1865, Gregor Mendel showed how traits are passed between generations through his classical pea crosses, giving us the first insight into the heritable basis of phenotypic variation [1]. Mendel’s findings revolutionized the concept of genotype-phenotype relationships and laid the foundation for modern genetics. However, our understanding of the spectrum and continuum between Mendelian and non-Mendelian diseases remains incomplete, and more work is needed to fully unravel the mechanisms underlying human diseases [2].

Mendelian diseases such as sickle cell anemia are characterized by monogenic genetic defects that result in discrete phenotypic differences [3]. Such Mendelian mutations are thought to segregate in predictable patterns, similar to the simple traits Mendel demonstrated in his pea crosses. Indeed, genetic mapping in family-based studies has led to remarkable discoveries of rare chromosomal abnormalities in patients with Mendelian diseases such as Duchenne muscular dystrophy [4]. However, even monogenic diseases follow a Mendelian inheritance pattern only sporadically. For example, in cystic fibrosis (CF), which has nearly 2000 mutant alleles in the primary causative gene Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and six other loci associated with but not causing the disease, patients exhibit considerable interindividual variability in symptom severity [5, 6]. Thus, there is no pure Mendelian inheritance [7] or, in other words, there are essentially no simple diseases [8].

In Mendelian diseases, mutations in critical genes are usually embryologically lethal, which explains the low prevalence of Mendelian disorders in natural populations [9]. In contrast, common forms of human disease such as diabetes, heart disease, and cancer occur in previously healthy individuals, and instead of dominant disease-causing alleles, many weak genetic factors exert miniscule and accumulative effects on phenotypic outcomes. This multifactorial nature of complex diseases, which are either oligogenic or polygenic [10], means that they do not strictly adhere to Mendelian inheritance patterns in conventional mapping analyses, as segregation of genetic variants in the recombinant offspring of genetically distinct parents can easily hide extreme phenotypes and mask association signals. Therefore, researchers have developed a threshold model that assumes that there is a distribution of susceptibility for a particular trait in the population and that the trait only occurs when a threshold is exceeded [11]. This model could explain ‘all or none’ phenotypes such as cleft palate and why relatives of affected individuals are at higher risk of multifactorial traits such as hypertension or diabetes than the general population [12].

With the advent of genome-wide association studies (GWAS), which use a large sample of unrelated individuals, significant progress has been made in reliably identifying genes that influence the risk of complex diseases [13]. However, even though many thousands of disease susceptibility loci have been characterized, challenges remain, such as the ‘dark matter of inheritance’ that cannot be assigned for most complex traits [14]. Several explanations have been proposed for this, including numerous low-influence variants, rare variants, poorly recognized structural variants, and inadequate estimation of gene-gene and gene-environment interactions [15].

Gene interaction was first demonstrated in retinitis pigmentosa (RP). Since the structural integrity of retinal photoreceptors depends on the functional complexes formed by Retinal Degeneration Slow (RDS) and Rod Outer segment Membrane protein 1 (ROM1), mutations at discrete loci disrupt digenic interactions and produce the same phenotype as alleles of the same locus [16, 17]. This is a perfect example of how pushing the boundaries of Mendelian genetics can help us unravel the true physiological and cellular nature of complex diseases.

In addition to gene-gene interactions, gene-environment interactions also contribute to quantitative traits and trigger the occurrence of complex diseases such as asthma, which are influenced by numerous genetic and nongenetic factors [18]. Environmental factors can also influence traits epigenetically. For example, the more methyl donors such as folic acid or vitamin B12 are present in the diet of young mice, the higher the frequency of methylation at the CpG site of the agouti gene and the darker the coat coloration in adulthood [19, 20].

Our understanding of the causes of disease has evolved from a simplified paradigm of the Mendelian model (one variant-one disease) to a more sophisticated polygenic model. Expanding Mendelian concepts and constructing theoretical models with higher complexity is the first step toward creating a conceptual continuum between Mendelian and non-Mendelian genetic traits. In the long term, genomics and phenomics will continue to be inexhaustible sources of information to elucidate the genetic architecture of both single gene anomalies and complex diseases and to enable more personalized diagnosis and treatment.

• Mendel, J.G., Versuche u ̈ber Pflanzenhybriden Verhandlungen des naturforschenden Vereines in Brünn, Bd. IV für das Jahr, Abhandlungen. 1865: p. 3-47.
• Badano, J.L. and N. Katsanis, Beyond Mendel: an evolving view of human genetic disease transmission. Nat Rev Genet, 2002. 3(10): p. 779-89.
• Steinberg, M.H. and A.H. Adewoye, Modifier genes and sickle cell anemia. Curr Opin Hematol, 2006. 13(3): p. 131-6.
• Monaco, A.P., et al., Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature, 1986. 323(6089): p. 646-50.
• Drumm, M.L., A.G. Ziady, and P.B. Davis, Genetic variation and clinical heterogeneity in cystic fibrosis. Annu Rev Pathol, 2012. 7: p. 267-82.
• Emond, M.J., et al., Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis. Nat Genet, 2012. 44(8): p. 886-9.
• Van Heyningen, V. and P.L. Yeyati, Mechanisms of non-Mendelian inheritance in genetic disease. Hum Mol Genet, 2004. 13 Spec No 2: p. R225-33.
• Dean, M., Approaches to identify genes for complex human diseases: lessons from Mendelian disorders. Hum Mutat, 2003. 22(4): p. 261-74.
• Quintana-Murci, L. and L.B. Barreiro, The role played by natural selection on Mendelian traits in humans. Ann N Y Acad Sci, 2010. 1214: p. 1-17.
• Assimes, T.L. and P.S. de Vries, Making the Most out of Mendel’s Laws in Complex Coronary Artery Disease. J Am Coll Cardiol, 2018. 72(3): p. 311-313.
• Wright, S., An Analysis of Variability in Number of Digits in an Inbred Strain of Guinea Pigs. Genetics, 1934. 19(6): p. 506-36.
• Korf, B.R., Basic genetics. Prim Care, 2004. 31(3): p. 461-78, vii.
• Crawford, N.P., Deciphering the Dark Matter of Complex Genetic Inheritance. Cell Syst, 2016. 2(3): p. 144-6.
• Kere, J., Genetics of complex disorders. Biochem Biophys Res Commun, 2010. 396(1): p. 143-6.
• Zuk, O., et al., The mystery of missing heritability: Genetic interactions create phantom heritability. Proc Natl Acad Sci U S A, 2012. 109(4): p. 1193-8.
• Clarke, G., et al., Rom-1 is required for rod photoreceptor viability and the regulation of disk morphogenesis. Nat Genet, 2000. 25(1): p. 67-73.
• Travis, G.H., et al., Identification of a photoreceptor-specific mRNA encoded by the gene responsible for retinal degeneration slow (rds). Nature, 1989. 338(6210): p. 70-3.
• Papi, A., et al., Asthma. Lancet, 2018. 391(10122): p. 783-800.
• Wolff, G.L., et al., Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. FASEB J, 1998. 12(11): p. 949-57.
• Waterland, R.A. and R.L. Jirtle, Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol, 2003. 23(15): p. 5293-300.

Honorable Mentions

Lena Chae Glenbrook South High School Glenview, Illinois Teacher: Mrs. Marianne Gudmundsson

Angelina Jolie, a famous actress, underwent bilateral mastectomy and oophorectomy to prevent hereditary breast and ovarian cancer that is prevalent in her family [1]. This was only possible because she was able to predict her risk of developing these cancers in her lifetime, which was substantially high enough to warrant prevention surgery. We now know that germline mutations found in BRCA1/2 genes are responsible for hereditary breast and ovarian cancer syndrome transmitted in an autosomal dominant fashion [2]. This discovery was made possible through progress in genetics which began with Mendel’s experiments in the 1800s [3].

Mendel’s discovery helped us better understand Mendelian disorders that involve single-gene mutations. First, the principles of inheritance found in plants opened up opportunities for scientists to apply their observations to patterns they noticed across human generations. This progress towards human studies from plants, helped scientists dissect human diseases that are inherited in a systematic manner. Second, Mendel’s discoveries allowed us to discover and understand the genetic material known as DNA. Because of Mendel’s observations, Watson and Crick were able to demonstrate the structure of the DNA molecule through their discovery of the double helix [4]. The Human Genome Project led by Craig Venter and Francis Collins laid the foundation for us to locate genes responsible for pathogenesis [5]. Third, understanding both the inheritance pattern of specific human hereditary diseases, along with the knowledge of the sequences in the human genome, contributed to the specific discovery of the mutations in such hereditary diseases. For instance, mutations in the HTT gene can cause Huntington’s disease [6], while mutations in the CFTR gene can cause cystic fibrosis [7]. Due to Mendel’s original discovery and experiments, scientists have been able to link genetics to human pathology.

The study of Mendelian disorders aided in a better understanding of complex diseases in two different ways. First, pedigree studies, or family tree analysis, were used to study monogenic Mendelian disorders with high penetrance; this led to a realization that many human diseases cannot be explained by the Mendelian principle of inheritance. Except for a few hereditary diseases, most human diseases involve more than one gene abnormality when comparing the affected versus unaffected members within a family. This finding led to the concept of stepwise multigene abnormalities and environmental interaction with respect to pathogenesis. Second, Genome-Wide Association Studies (GWAS), which is the population-level study of genes and human diseases, could be understood as an aggregate of linkage analyses based on Mendelian principles [8]. It also extended the field of genetics. GWAS made it possible for scientists to define the role of single DNA mutations in complex diseases. Hundreds of thousands of single-nucleotide polymorphisms (SNPs) can be tested to explore the associations between these variants and disease in larger populations. For example, through the GWAS study, over 40 loci have been found to be associated with Type 2 Diabetes Mellitus (DM) [9]. Another highly heritable psychiatric disorder, schizophrenia, is linked with 108 genetic loci according to a GWAS consisting of more than 150,000 samples [10]. An improved understanding of comprehensive genomic mutations involved in such complex diseases led to the creation of a risk profile score (RPS), which is currently used to predict the risk of such disease development [11].

However, human diseases can sometimes be more than just changes in DNA. Both pedigree analysis and GWAS assume that hereditary diseases can fully be explained by genetic mutations. But epigenetic changes can be equally or more important [12]. Epigenetic processes such as DNA methylation or histone modifications, triggered by environmental and behavioral changes, may turn the target gene expressions “on” or “off”. Furthermore, protein modification may also play a role in pathogenesis. Therefore, to better understand complex diseases, it is critical to utilize both the study of genetics stemming from Mendel’s discoveries, and the non-genetic processes including epigenetics, transcriptomics, and proteomics [12].

In summary, Mendel’s discovery helped us better understand Mendelian disorders but also more complex diseases. Owing to Mendel’s principles of inheritance, scientists are now equipped with platforms and techniques to analyze both Mendelian disorders and complex diseases. Individualized treatments are now made possible through accurate diagnoses including identification of mutations leading to disease. Just as Angelina Jolie was able to prevent hereditary breast and ovarian cancer through germline DNA profiling, further in-depth DNA screening in a population can lead to a significant reduction in the risk of various hereditary and complex diseases.

• Jolie, A. (2013, May 14). My Medical Choice. New York Times, pp. 25–25.
• Rebbeck, T. R., Friebel, T., Lynch, H. T., Neuhausen, S. L., van ’t Veer, L., Garber, J. E., Evans, G. R., Narod, S. A., Isaacs, C., Matloff, E., Daly, M. B., Olopade, O. I., & Weber, B. L. (2004). Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: THE PROSE Study Group. Journal of Clinical Oncology, 22(6), 1055–1062. https://doi.org/10.1200/jco.2004.04.188
• B. (2021, May 21). Gregor Mendel. Biography. https://www.biography.com/scientist/gregor-mendel
• Pray, L. (2008) Discovery of DNA structure and function: Watson and Crick. Nature Education 1(1):100
• Adams, J. (2008) Sequencing human genome: the contributions of Francis Collins and Craig Venter. Nature Education 1(1):133
• Conneally P. M. (1984). Huntington disease: genetics and epidemiology. American journal of human genetics, 36(3), 506–526.
• Gallati S. (2003). Genetics of cystic fibrosis. Seminars in respiratory and critical care medicine, 24(6), 629–638. https://doi.org/10.1055/s-2004-815659
• Manolio T. A. (2010). Genomewide association studies and assessment of the risk of disease. The New England journal of medicine, 363(2), 166–176. https://doi.org/10.1056/NEJMra0905980
• Hakonarson, H., & Grant, S. F. (2011). Genome-wide association studies (GWAS): impact on elucidating the aetiology of diabetes. Diabetes/metabolism research and reviews, 27(7), 685–696. https://doi.org/10.1002/dmrr.1221
• Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511(7510), 421–427. https://doi.org/10.1038/nature13595
• Xiao, E., Chen, Q., Goldman, A. L., Tan, H. Y., Healy, K., Zoltick, B., Das, S., Kolachana, B., Callicott, J. H., Dickinson, D., Berman, K. F., Weinberger, D. R., & Mattay, V. S. (2017). Late-Onset Alzheimer’s Disease Polygenic Risk Profile Score Predicts Hippocampal Function. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2(8), 673–679. https://doi.org/10.1016/j.bpsc.2017.08.004
• Centers for Disease Control and Prevention. (2020, August 3). What is epigenetics? Centers for Disease Control and Prevention. Retrieved March 1, 2022, from https://www.cdc.gov/genomics/disease/epigenetics.htm

  Aadit Jain International Academy Bloomfield Hills, Michigan Teacher: Mrs. Suzanne Monck

Nearly two centuries ago, Gregor Mendel launched the scientific community into the vast world of genetics and diseases with his experiments on the common pea plant (1,2). Specifically, his principles have been instrumental in the plethora of discoveries that have been made in Mendelian disorders. With around 400 million people worldwide suffering from one of the 7,000 Mendelian disorders, much research today centers on identifying the genetic causes of these diseases (3). While Mendel was unaware of genes and DNA when he conducted his study (2), his discoveries kickstarted the substantial research that scientists have undertaken on Mendelian disorders.

Mendel’s principles have directly allowed scientists to understand how Mendelian disorders are inherited. For example, his notable discovery that phenotypes of recessive traits can skip generations (2) applies to Mendelian disorders in the case of carriers (4). These are individuals who may not display the disorder phenotype but still carry and can pass on the altered gene (4). Therefore, it is essential to analyze pedigrees of affected families to determine whether the disease-causing gene has a dominant or recessive phenotype. Importantly, this knowledge helps genetics professionals understand the risk that individuals have of passing on a disorder (5). For example, a person who suffers from an autosomal dominant disorder bears a 50% chance of passing the affected gene to each offspring (5). In contrast, two heterozygous parents for an autosomal recessive disorder have a 25% chance of having an offspring affected with the disorder with each pregnancy (5).

Mendel’s principles of uniformity, segregation, and independent assortment demonstrate how genes and alleles are inherited (2). However, subsequent research revealed exceptions such as the sex-linked pattern of inheritance (2,6). Contrary to inheritance of autosomal single-gene diseases, males and females receive a different number of copies of the implicated gene for sex-linked disorders due to their respective pairs of sex chromosomes (1). As a result, sex-linked diseases tend to be prevalent in only one gender (1). For example, Hemophilia A, a blood clotting disorder, typically affects only males because it is an X chromosome-linked recessive disease (1). It is evident that although Mendel’s principles have laid a strong foundation of inheritance patterns, the scientific community’s understanding of Mendelian disorders is greatly enhanced through new research.

Mendel’s discoveries have been fundamental in developing effective methods to test for disorders. With the understanding that the same allele codes for a specific phenotype, researchers have individuals with the same phenotype disorder undergo sequencing in order to identify the defective gene (7). Such was the case in 2010, when scientists discovered that the MLL2 gene was responsible for Kabuki syndrome: 7 out of 10 individuals in the group suffered from a loss of function in that gene (7). Since then, with the Matchmaker Exchange (MME) and the Monarch Initiative, there has been an emphasis on sharing phenotype and genotype data in order to discover new Mendelian disorders (7).

Although complex diseases are influenced by several factors and do not fully follow the inheritance patterns (8), investigating Mendelian disorders can provide insight into the implicated genes and pathways in them. By analyzing data from established databases, genetic researchers found that in fact 54% of Mendelian disease genes play a notable role in complex diseases as well (9). Genes underlying both diseases tend to be associated with more phenotypes and protein interactions, so studying them can be quite useful in understanding Mendelian disorders and consequently complex diseases (9). In some cases, individuals diagnosed with complex diseases have an underlying monogenic condition that is the cause (10). This specifically highlights the significance of research techniques for single-gene disorders to investigations of complex diseases. In the case of hypercholesterolemia, for example, monogenic forms of the disease were used to determine the impact of lipid transport and to identify the involved pathways in the development of this complex disease (10).

Research on Mendelian disorders has helped scientists understand gene function and mechanisms overall. Studying single-gene disorders can further provide insight into the genetic pathways of complex diseases (9). In fact, with genome-wide association studies (GWAS) into single nucleotide polymorphisms (SNP), thousands of genes implicated in complex diseases have been identified (9). Although many details of complex diseases have been established, heritable aspects still remain uncertain (9). Overall, knowledge of Mendel’s principles and Mendelian disorders will be essential in this case and others as research delves further into disease processes.

• Chial, Heidi. “Mendelian Genetics: Patterns of Inheritance and Single-Gene Disorders.” Edited by Terry McGuire. Nature Education, 2008, www.nature.com/scitable/topicpage/mendelian-genetics-patterns-of-inheritance-and-single-966/.
• Miko, Ilona. “Gregor Mendel and the Principles of Inheritance.” Edited by Terry McGuire. Nature Education, 2008, www.nature.com/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593/.
• Ganguly, Prabarna. “NIH funds new effort to discover genetic causes of single-gene disorders.” National Human Genome Research Institute, 15 July 2021, www.genome.gov/news/news-release/NIH-funds-new-effort-to-discover-genetic-causes-of-single-gene-disorders.
• “Carrier.” National Human Genome Institute, www.genome.gov/genetics-glossary/Carrier.
• “If a genetic disorder runs in my family, what are the chances that my children will have the condition?” MedlinePlus, medlineplus.gov/genetics/understanding/inheritance/riskassessment/.
• Nickle, Todd, and Isabelle Barrette-Ng. “3.5: Sex-Linkage- An Exception to Mendel’s First Law.” Biology LibreTexts, 3 Jan. 2021, bio.libretexts.org/Bookshelves/Genetics/Book%3A_Online_Open_Genetics_(Nickle_and_Barrette-Ng)/03%3A_Genetic_Analysis_of_Single_Genes/3.05%3A__Sex-Linkage-_An_Exception_to_Mendels_First_Law.
• Seaby, Eleanor G., et al. “Strategies to Uplift Novel Mendelian Gene Discovery for Improved Clinical Outcomes.” Frontiers in Genetics, 17 June 2021, www.frontiersin.org/articles/10.3389/fgene.2021.674295/full.
• Craig, Johanna. “Complex Diseases: Research and Applications.” Edited by Alexandre Vieira. Nature Education, 2008, www.nature.com/scitable/topicpage/complex-diseases-research-and-applications-748/.
• Jin, Wenfei, et al. “A systematic characterization of genes underlying both complex and Mendelian diseases.” Human Molecular Genetics, vol. 21, no. 7, 20 Dec. 2011, academic.oup.com/hmg/article/21/7/1611/2900796.
• Chong, Jessica X., et al. “The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities.” Science Direct, www.sciencedirect.com/science/article/pii/S0002929715002451.

  Sharanya Ravishanker Conestoga High School Berwyn, Pennsylvania Teacher: Mrs. Liz Gallo

Through his genetic experimentations with pea plants, Gregor Mendel established the following Laws of Inheritance that remain critical to our understanding of heredity: The Law of Segregation, The Law of Independent Assortment, and The Law of Dominance (1, 2). In summation, phenotypes—expressed characteristics—are correlated with the type of allele inherited from each parent during gamete formation when genes randomly separate. If an allele is dominant, it is expressed; if an allele is recessive, the associated characteristic will not be displayed unless a matching recessive allele is inherited from the other parent.

These laws and inheritance patterns form the basis of our understanding of Mendelian disorders, rare monogenic diseases caused by alterations—often single-nucleotide polymorphisms (SNPs) and corresponding amino-acid substitutions resulting in the production of unwanted or malfunctioning proteins—in just one of the 25,000 genes in a human genome (3, 4, 5). These mutations typically occur in germline cells, and are thus passed down through DNA to every cell of the offspring (6). Well known Mendelian diseases include cystic fibrosis, sickle cell anemia, and Huntington’s disease.

Through the application of Mendel’s Laws, geneticists have identified five modes of inheritance for Mendelian disorders: autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and mitochondrial (7), paving the way for geneticists to accurately diagnose Mendelian disorders, a step crucial in providing patients with the treatment and specific care they require, as well as revealing significant information vital to the family planning of individuals who carry recessive alleles for threatening disorders. Genealogical records and pedigree analyses have been utilized to trace inheritance through families, but next-generation sequencing technology has gained traction as a method to detect changes in nucleotide orders. Exome-sequencing, for example, focuses on identifying variants in the protein-coding region (exons), and is regarded as cost-effective due to its specificity, focusing on only 1% of the human genome (8, 9, 10). On the other hand, whole genome sequencing can be advocated for due to its capture of DNA variations outside of exons as well as within. Still, as benign polymorphisms are highly prevalent and frequent, entire genome sequencing can make it difficult to prioritize harmful mutations due to the sheer amount of variants shown (9, 11). RNA sequencing can provide support here by quantifying the effect to which a gene is expressed (11, 12 ).

Information gathered from these methods and Mendelian principles regarding dominance also enable geneticists to determine trait-associated gene loci, allowing for a better understanding of protein formation, modification, and function (13). In fact, as Rockefeller University president and accomplished biochemist Dr. Richard Lifton notes, understanding the connection between genes and expressed traits—SNP and product—has served as “starting points for understanding disease and human biology in general”. For example, analysis of a Mendelian form of hypertension resulted in the discovery of a pathway regulating salt reabsorption and potassium secretion in the kidney (14). Similar discoveries of pathways as a result of studies into Mendelian disorders can increase our understanding and ability to treat complex disorders such as cancer, even if these diseases disregard Mendelian principles of inheritance on account of being caused by numerous genetic and environmental factors interacting with one another.

In the same vein, understanding the results of SNP modification allows for research into the genetic susceptibility for various complex disorders and its correlation with environmental exposure. For example, it was determined that individuals whose genotype is homozygous recessive for xeroderma pigmentosum are highly susceptible to UV light related disorders due to mutations in DNA-repairing genes. Similarly, individuals with a mutation in the Alpha-1 gene are at a greater risk for emphysema, especially through smoking, though the mutation itself isn’t causative of the disease (15). The aforementioned linkages between genes and phenotypes would not be possible without the research into Mendelian disorders that revealed crucial information regarding the impacts of individual genes on expressed phenotypes.

Overall, studies into Mendelian diseases—in turn impacted by the understanding of Mendel’s Laws of Inheritance—have contributed significantly to our knowledge of more complex disorders. This knowledge will prove beneficial in developing more efficient medicinal drugs and therapies that effectively target detrimental proteins or alter gene expression to receive desired results (16). As Dr. James Luspki, Professor of Molecular and Human Genetics at Baylor College of Medicine says, “We’re on the threshold of new explanations of disease inheritance and development” (14). Resulting discoveries from studies into Mendelian principles and disorders will undoubtedly clear the way towards greater advancements in our ability to treat complex disorders.

References/Citations: Mendel’s Law of Segregation. 15 Aug. 2020, https://bio.libretexts.org/@go/page/13271. “Inheritance of Traits by Offspring Follows Predictable Rules.” Nature. Scitable by Nature Education, www.nature.com/scitable/topicpage/inheritance-of-traits-by-offspring-follows-predictable-6524925/#:~:text=One%20allele%20for%20every%20gene,same%22)%20for%20that%20allele. Accessed 22 Feb. 2022. Jackson, Maria et al. “The genetic basis of disease.” Essays in biochemistry vol. 62,5 643-723. 2 Dec. 2018, doi:10.1042/EBC20170053 Coding single-nucleotide polymorphisms associated with complex vs. Mendelian disease: Evolutionary evidence for differences in molecular effects. Paul D. Thomas, Anish Kejariwal. Proceedings of the National Academy of Sciences Oct 2004, 101 (43) 15398-15403; DOI: 10.1073/pnas.0404380101 The 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature 526, 68–74 (2015). https://doi.org/10.1038/nature15393 “Germline Mutation.” National Cancer Institute, www.cancer.gov/publications/ dictionaries/cancer-terms/def/germline-mutation. Accessed 22 Feb. 2022. Genetic Alliance; District of Columbia Department of Health. Understanding Genetics: A District of Columbia Guide for Patients and Health Professionals. Washington (DC): Genetic Alliance; 2010 Feb 17. Appendix B, Classic Mendelian Genetics (Patterns of Inheritance) Available from: https://www.ncbi.nlm.nih.gov/books/NBK132145/ “Exome Sequencing.” Science Direct, 2018, www.sciencedirect.com/topics/ agricultural-and-biological-sciences/exome-sequencing. Accessed 22 Feb. 2022. “What are whole exome sequencing and whole genome sequencing?” MedlinePlus, 28. July 2021, medlineplus.gov/genetics/understanding/testing/sequencing/. Accessed 22 Feb. 2022. Bamshad, M., Ng, S., Bigham, A. et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet 12, 745–755 (2011). https://doi.org/10.1038/nrg3031 Byron, S., Van Keuren-Jensen, K., Engelthaler, D. et al. Translating RNA sequencing into clinical diagnostics: opportunities and challenges. Nat Rev Genet 17, 257–271 (2016). https://doi.org/10.1038/nrg.2016.10 Wang, Zhong et al. “RNA-Seq: a revolutionary tool for transcriptomics.” Nature reviews. Genetics vol. 10,1 (2009): 57-63. doi:10.1038/nrg2484 Chial, H. (2008) Rare Genetic Disorders: Learning About Genetic Disease Through Gene Mapping, SNPs, and Microarray Data. Nature Education 1(1):192 Benowitz, Steven. “Centers for Mendelian Genomics uncovering the genomic basis of hundreds of rare conditions.” National Human Genome Research Institute, 6 Aug. 2015, www.genome.gov/news/news-release/ Centers-for-Mendelian-Genomics-uncovering-the-genomic-basis-of-hundreds-of-rare-conditions. Accessed 22 Feb. 2022. Craig, J. (2008) Complex diseases: Research and applications. Nature Education 1(1):184 Heguy, A et al. “Gene expression as a target for new drug discovery.” Gene expression vol. 4,6 (1995): 337-44.

Zhiyuan Shi BASIS International School Hangzhou Hangzhou, China Teacher: Dr. Dongchen Xu

Mendelian theories provided the foundations for the contemporary understanding of heredity. Mendel’s legacy has been particularly beneficial to medical sciences, where research on inheritance patterns of Mendelian disorders has been made possible through utilizing Mendel’s theory. Mendelian theories serve as robust models for evaluating and verifying the inheritance patterns of particular diseases. Even though our current understanding of genetics has moved beyond the Mendelian model, studying certain Mendelian disorders such as oculocutaneous albinism can lead to an improved understanding of complex disorders with polygenic inheritance.

Oculocutaneous albinism is an autosomal-recessive condition caused by the extremely low level of melanin biosynthesis due to mainly four genes (1, 2). Individuals with this illness will also experience whitening of the skin, certain degrees of vision deterioration, and a higher risk of contracting skin cancer due to the lack of dermal melanin (1, 2); understanding the underlying inheritance pattern of albinism would be advantageous towards the prevention of skin cancers. The genetic cause of oculocutaneous albinism can be explained by Mendelian genetics. The disorder is autosomal, meaning neither the gender of the parents nor the gender of the offspring plays a role in its inheritance. The disorder is recessive, meaning both parents must be carriers for birthing an Albino child (3). Through examination of information like the ones above and specific pathology of the disorder, one can establish critical predictions of an offspring’s genotype based on the family’s history. Such analyses enable us to speculate and reconstruct pedigrees for Mendelian disorders using family history. Information regarding Mendelian disorders running in the family and the possible genotypes for offsprings (50% risk of being carriers and 25% risk of being affected) are important to parents seeking family planning suggestions, reinforcing prevention.

Mendelian and non-Mendelian diseases are often regarded as segregated families of genetic disorders. Complex non-Mendelian disorders involve polygenic traits that don’t follow Mendelian disorders’ monogenic properties. However, genes responsible for monogenic diseases correspondingly contribute to the expression of polygenic traits (4). Mendelian disorders are key in providing the individual monogenic components that contribute to complex disease’s polygenic causes. Some of the gene variants responsible for skin pigmentation disorder and skin cancer are the exact genes responsible for the pigment deficiency in the Mendelian disorder oculocutaneous albinism. The 2 most notable ones are variants of the gene TYRP1, a gene coding for the protein tyrosinase-related protein 1, which contributes to melanosome integrity; and gene SLC45A2, which code for a cation exchange protein that transports material required for melanin synthesis into the melanosome (2, 6, 7). Variants of these genes are inherited as monogenic traits, and studies show they contribute to the formation of polygenic skin cancers such as squamous skin cell carcinoma (8). Mendelian inheritance of other variants of the 2 listed genes can even cause other polygenic skin cancers such as melanoma, exhibiting excessive melanin levels. Research showed that heterozygous variants of TYRP1 and SLC45A2 are overrepresented in families with multiple cases of melanoma (9).

Although overrepresentation of SLC45A2 is found in cases of melanoma, variants of the gene can have the opposite effect. A meta-analysis conducted by Ibarrola-Villava et al., 2012, revealed that the SLC45A2 p.Phe374Leu variant had an odds ratio of 0.41 for melanoma (p = 3.50 * 10^-17), enough for concluding that SLC45A2 p.Phe374Leu negatively correlates with melanoma formation (13). This and the previous evidence suggest that factors affecting melanin concentration, one of the key determinants for the presence of different types of polygenic skin cancers, could be partially attributed to the variants of TYRPI and SLC45A2 genes that involve Mendelian inheritance mechanisms.

Another polygenic disorder with Mendelian roots is growth disorder, in which several genes that contribute to the complex disorder of growth disorders are monogenic. For instance, one factor contributing to the common short stature in growth disorders such as dwarfism is the autosomal dominant Mendelian disorder achondroplasia, resulting from the Mendelian inheritance of the mutated FGFR3 gene (10,11). Another monogenic disorder that contributes to growth disorders such as dwarfism is growth hormone deficiency, an autosomal recessive disorder resulting from the mutation and Mendelian inheritance of the mutated GH1 or GHRHR gene (12).

The Mendelian factors underlying both skin cancer and growth disorders demonstrated the value of studying Mendelian inheritance patterns in complex disorders. Although Mendelian diseases only contribute to a small proportion of all known human disorders, understanding their underlying mechanism and pattern, and utilizing them alongside conventional methods for the investigation of complex diseases is of great importance(5), and would produce spectacular innovations in the field of genetics.

• Marçon, C. R., & Maia, M. (2019). Albinism: Epidemiology, genetics, cutaneous characterization, psychosocial factors. Anais brasileiros de dermatologia. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857599/
• Grønskov, K., Ek, J., & Brondum-Nielsen, K. (2007, November 2). Oculocutaneous albinism. Orphanet journal of rare diseases. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211462/
• Gulani, A. (2021, May 8). Genetics, autosomal recessive. StatPearls [Internet]. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK546620/
• Franić, S., Groen-Blokhuis, M. M., Dolan, C. V., Kattenberg, M. V., Pool, R., Xiao, X., Scheet, P. A., Ehli, E. A., Davies, G. E., van der Sluis, S., Abdellaoui, A., Hansell, N. K., Martin, N. G., Hudziak, J. J., van Beijsterveldt, C. E. M., Swagerman, S. C., Hulshoff Pol, H. E., de Geus, E. J. C., Bartels, M., … Boomsma, D. I. (2015, October). Intelligence: Shared genetic basis between Mendelian disorders and a polygenic trait. European journal of human genetics : EJHG. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4592100/
• Lango Allen, H., Estrada, K., Lettre, G., Berndt, S. I., Weedon, M. N., Rivadeneira, F., Willer, C. J., Jackson, A. U., Vedantam, S., Raychaudhuri, S., Ferreira, T., Wood, A. R., Weyant, R. J., Segrè, A. V., Speliotes, E. K., Wheeler, E., Soranzo, N., Park, J.-H., Yang, J., … Hirschhorn, J. N. (2010, October 14). Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955183/
• Del Bino, S., Duval, C., & Bernerd, F. (2018, September 8). Clinical and biological characterization of skin pigmentation diversity and its consequences on UV impact. International journal of molecular sciences. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163216/
• Federico, J. R. (2021, August 27). Albinism. StatPearls [Internet]. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK519018/
• Board, P. D. Q. C. G. E. (2009, July 29). Genetics of Skin Cancer (PDQ®). PDQ Cancer Information Summaries [Internet]. Retrieved March 1, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK65895/
• Nathan, V., Johansson, P. A., Palmer, J. M., Howlie, M., Hamilton, H. R., Wadt, K., Jönsson, G., Brooks, K. M., Pritchard, A. L., & Hayward, N. K. (2019). Germline variants in oculocutaneous albinism genes and predisposition to familial cutaneous melanoma. Pigment Cell & Melanoma Research, 32(6), 854–863. https://doi.org/10.1111/pcmr.12804
• Krakow, D., & Rimoin, D. L. (2010, April 27). The skeletal dysplasias. Nature News. Retrieved March 1, 2022, from https://www.nature.com/articles/gim201054
• U.S. National Library of Medicine. (2020, August 18). Achondroplasia: Medlineplus genetics. MedlinePlus. Retrieved March 1, 2022, from https://medlineplus.gov/genetics/condition/achondroplasia/#inheritance
• U.S. National Library of Medicine. (2020, August 18). Isolated growth hormone deficiency: Medlineplus Genetics. MedlinePlus. Retrieved March 1, 2022, from https://medlineplus.gov/genetics/condition/isolated-growth-hormone-deficiency/
• Ibarrola-Villava, M., Hu, H.-H., Guedj, M., Fernandez, L. P., Descamps, V., Basset-Seguin, N., Bagot, M., Benssussan, A., Saiag, P., Fargnoli, M. C., Peris, K., Aviles, J. A., Lluch, A., Ribas, G., & Soufir, N. (2012). MC1R, SLC45A2 and Tyr genetic variants involved in melanoma susceptibility in southern European populations: Results from a meta-analysis. European Journal of Cancer, 48(14), 2183–2191. https://doi.org/10.1016/j.ejca.2012.03.006

Audric Thakur Reading School Reading, United Kingdom Teacher: Ms. Francis Howson

Mendel’s research intended to determine how characteristics of an individual were inherited by their offspring. At the time, the scientific community lacked the genotypic knowledge required to explain how genetic information was transferred to an individual¹. Only in 1826 did Augustin Sageret discover the idea of trait dominance³ (amid a cultural resurgence of Preformation Theory²), and so it was through observational study that Mendel developed the laws of heredity which ground our understanding of Mendelian disorders today.

Most famous of Mendel’s work are those regarding the rugosus locus and the presence or absence of the SBE1 gene⁴, phenotypically expressed by the distinctive ’round’ or ‘wrinkled’ shapes of pea pods respectively⁵. Specifically, he determined the recessive nature of the wrinkled trait through his monohybrid crossing of a uniformly heterozygous generation of pea plants (which themselves were the progeny of a homozygous-dominant and homozygous-recessive cross)⁵. Naturally, this uniform generation of heterozygous peas all possessed the round characteristic. However, Mendel proved that these peas retained their parents’ ‘elementen’⁵ (or more accurately, DNA), since they went on to produce offspring with characteristics from the grandparent generation, evidenced by the 3:1 ratio of round to wrinkled offspring – clear to us now through use of a Punnett square⁶. Of course, these results were the aggregate of a large sample size across several iterations⁵, and therefore incredibly precise (to the point of controversy⁷). As such, they formed the basis for his laws of heredity.

Deriving Mendel’s laws from his work on pea plants is critical to understanding monogenic conditions because their inheritance patterns are often identical⁸, enabling us to make accurate comparisons between the two. This is demonstrated by the Mendelian condition phenylketonuria (PKU)⁹-¹⁰, an autosomal recessive disorder caused by an absent PAH gene at the genetic locus 12q23.2¹⁰.

Citing national Newborn Screening Reports¹¹, 1.7606% of Caucasian-Americans (1996-2000) are heterozygous carriers of PKU. If I apply some simplified mathematics (i.e. ignoring lifestyle factors), the probability of both parents in a Caucasian-American household being carriers of PKU is 0.0310% (0.017606²). Therefore, as per the rules of inheritance followed by Mendel’s pea plants, 0.0077% (0.0310*0.25) of the Caucasian-American population should be expressors of PKU. According to the National Library of Medicine¹¹, the official estimate is 0.0075% – a remarkable example of the accuracy and utility of Mendel’s work, and how understanding and implementing his discoveries has relevant real-world significance, being comparable to large-scale medical statistics to this day.

Unfortunately, it must be noted that Mendelian disorders are an exceptional minority of genetic conditions – the emerging consensus that most exist on a spectrum from Mendelian conditions¹² (high gene penetrance and low gene-environment interaction¹³) to increasingly complex conditions (incomplete or varying gene penetrance and high gene-environment interaction¹³), and that complex disorders are influenced by a multitude of interconnected factors¹⁴. This is why scientists approach complex disorders by assessing risk of onset, rather than applying Mendelian rules of inheritance. Nevertheless, links between the genotypic expression of Mendelian conditions in an individual and the onset of associated complex disorders have been established in the last decade or so of scientific inquiry¹³.

Studies regarding Mendelian comorbidities alongside complex disorders have proved that genetic loci containing causal variants for both Mendelian disorders and complex disease tend to have a greater influence on the onset of a complex disorder compared to genes that pertain to risk factors for only that complex disorder¹³. This means, for an individual afflicted by a series of Mendelian disorders, the probability that they will develop a complex disorder whose determinant genes are simultaneously involved in expressing those Mendelian disorders is significantly higher¹³. For example, an increased risk of schizophrenia is involved with patients who carry genetic variants of Lujan-Fryns and velo-cardio-facial syndromes¹⁷ (clear correlation), and a higher likelihood of developing type-2 diabetes mellitus if the patient suffers from Huntington’s disease, Friedreich’s ataxia and beta-thalassemia¹⁵-¹⁶ (partially supported correlation). This demonstrates that Mendelian-associated genes are certainly influential in determining emergence of a complex disorder. Therefore, understanding inheritance patterns of these Mendelian conditions is essential to create an accurate way of ascertaining the risk of onset for more complex conditions.

Despite the elusive nature of inheritance patterns surrounding several complex disorders, insight can nevertheless be found in studying genes associated with Mendelian conditions. Due to their high penetrance and straightforward inheritance patterns¹³, these monogenic conditions are easy to diagnose and engage in research with, providing a unique foothold to better understand many complex conditions, and allowing us to form more realistic models to predict their onset¹⁸.

Note: citations from sources published prior to 2015 have been used for historical knowledge or to explain/discuss historical scientific experiments only. The exception to this is reference 15.

• Durmaz, A. A., Karaca, E., Demkow, U., Toruner, G., Schoumans, J., & Cogulu, O. (2015). Evolution of genetic techniques: Past, present, and beyond. BioMed research international. Retrieved February 28, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385642/
• Maienschein, J. (2005, October 11). Epigenesis and Preformationism. Stanford Encyclopedia of Philosophy. Retrieved February 28, 2022, from https://plato.stanford.edu/entries/epigenesis/#8
• Zirkle, C. (1951, June). Gregor Mendel & his Precursors. Retrieved February 28, 2022, from https://www.mun.ca/biology/scarr/Zirkle_%281951%29_Gregor_Mendel_&_his_Precursors,%20Isis_42,97-104.pdf
• Smith, A., & Martin, C. (2020, December 11). A history of wrinkled-seeded research in PEA. John Innes Centre. Retrieved February 28, 2022, from https://www.jic.ac.uk/advances/a-history-of-wrinkled-seeded-research-in-pea/
• Miko, I. (2008). Gregor Mendel and the Principles of Inheritance. Nature news. Retrieved February 28, 2022, from https://www.nature.com/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593/
• (while the citation doesn’t reference the SBE1 gene in particular, it does discuss other recessive pea plant traits, making it useful nevertheless) LibreTexts, O. S. (2021, September 22). 8.2: Laws of inheritance. Biology LibreTexts. Retrieved February 28, 2022, from https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Book%3A_Concepts_in_Biology_(OpenStax)/08%3A_Patterns_of_Inheritance/8.02%3A_Laws_of_Inheritace
• Radlick, G. (2015, October 9). Beyond mendelfisher – eprints.whiterose.ac.uk. Beyond the “Mendel-Fisher controversy”. Retrieved February 28, 2022, from https://eprints.whiterose.ac.uk/91201/2/BeyondMendelFisher091015%5B1%5D.pdf
• Chial, H. (2008). Mendelian Genetics: Patterns of Inheritance and Single-Gene Disorders. Nature news. Retrieved February 28, 2022, from https://www.nature.com/scitable/topicpage/mendelian-genetics-patterns-of-inheritance-and-single-966/
• NHS. (2019, December 3). Phenylketonuria. NHS choices. Retrieved February 28, 2022, from https://www.nhs.uk/conditions/phenylketonuria/
• Hillert, A., Anikster, Y., Belanger-Quintana, A., Burlina, A., Burton, B. K., Carducci, C., Chiesa, A. E., Christodoulou, J., Đorđević, M., Desviat, L. R., Eliyahu, A., Evers, R. A. F., Fajkusova, L., Feillet, F., Bonfim-Freitas, P. E., Giżewska, M., Gundorova, P., Karall, D., & Blau, N. (2020, July 14). The genetic landscape and epidemiology of phenylketonuria. The American Journal of Human Genetics. Retrieved February 28, 2022, from https://www.sciencedirect.com/science/article/pii/S0002929720301944
• Arbesman, J., Ravichandran, S., Funchain, P., & Thompson, C. L. (2018, July 1). Melanoma cases demonstrate increased carrier frequency of phenylketonuria/hyperphenylalanemia mutations. Pigment cell & melanoma research. Retrieved February 28, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6013363/
• 12.Freund, M. K., Burch, K. S., Shi, H., Mancuso, N., Kichaev, G., Garske, K. M., Pan, D. Z., Miao, Z., Mohlke, K. L., Laakso, M., Pajukanta, P., Pasaniuc, B., & Arboleda, V. A. (2018, October 4). Phenotype-specific enrichment of mendelian disorder genes near gwas regions across 62 complex traits. The American Journal of Human Genetics. Retrieved February 28, 2022, from https://www.sciencedirect.com/science/article/pii/S0002929718302854
• Spataro, N., Rodríguez, J. A., Navarro, A., & Bosch, E. (2017, February 1). Properties of human disease genes and the role of genes linked to mendelian disorders in complex disease aetiology. Human molecular genetics. Retrieved February 28, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409085/
• Yong, S. Y., Raben, T. G., Lello, L., & Hsu, S. D. H. (2020, July 21). Genetic architecture of complex traits and disease risk predictors. Nature News. Retrieved February 28, 2022, from https://www.nature.com/articles/s41598-020-68881-8
• Blair, D. R., Lyttle, C., Mortensen, J., Bearden, C., Jensen, A., Khiabanian, H., Melamed, R., Rabadan, R., Bernsdam, E., Brunak, S., Jensen, L., Nicolae, D., Shah, N., Grossman, R., Cox, N., White, K., & Rzhetsky, A. (2013, September 26). A Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk. Define_me. Retrieved February 28, 2022, from https://www.cell.com/fulltext/S0092-8674(13)01024-6
• (not disproving, but cautioning the results of 15) Montojo, M. T., Aganzo, M., & González, N. (2017, September 29). Huntington’s disease and diabetes: Chronological sequence of its association. Journal of Huntington’s disease. Retrieved February 28, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676851/
• Rizvi, S., Khan, A. M., Saeed, H., Aribara, A. M., Carrington, A., Griffiths, A., & Mohit, A. (2018, August 14). Schizophrenia in digeorge syndrome: A unique case report. Cureus. Retrieved February 28, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188160/
• Jordan, D., & Do, R. (2018, April 11). Using full genomic information to predict disease: Breaking down the barriers between complex and Mendelian Diseases. Annual Reviews. Retrieved February 28, 2022, from https://www.annualreviews.org/doi/10.1146/annurev-genom-083117-021136

Emma Tse Cheltenham Ladies’ College Cheltenham, United Kingdom Teacher: Ms. Helen Stuart

Between 1856 and 1865, Gregor Mendel conducted experiments on garden peas to investigate inheritance (1). His observations, notably his three principles of inheritance, form the basis of scientists’ grasp of monogenic (Mendelian) disorders today, which are caused by mutations in a single gene (2). Before Mendel’s discoveries, it was widely accepted that traits of progeny were a combination of those of each parent. However, when he cross-pollinated smooth-seeded peas with wrinkled-seeded peas, the offspring (F1 generation) only had smooth seeds as opposed to semi-wrinkled seeds. This gave rise to the concept of dominant traits, as well as his first principle: the principle of uniformity, which states that all offspring of parents with two distinct traits will inherit the same (dominant) trait of one parent (3). Mendel discovered recessive traits by self-pollinating a plant from the F1 generation, noting that its offspring (F2 generation) displayed a 3:1 ratio of smooth to wrinkled seeds (3). This proportion indicated that there was a hidden form of the trait, which Mendel acknowledged passed down to the F2 generation. Mendel also proposed the idea of each parent giving their offspring one heritable unit which he called “elementen”, and scientists now recognise this as genes – more specifically, alleles (2). Sickle-cell anaemia is a well-characterised autosomal recessive disease; those affected inherit two copies of a mutant beta-globin gene (1). Huntington’s disease, on the other hand, is an autosomal dominant disorder in which affected individuals possess at least one copy of the mutant HTT gene (1).

Mendelian disorders are relatively uncommon; on the other hand, complex diseases such as asthma and multiple sclerosis are more prevalent and arise from a combination of genetic, environmental and lifestyle factors (4). Therefore, complex diseases do not entirely adhere to Mendelian inheritance. They can be oligogenic or polygenic, meaning there are multiple genes each with their own mutations contributing to the disease’s phenotype (5). Studying Mendelian disorders allows researchers to examine the mutant gene’s effects on human biochemistry and physiology, thus furthering our understanding of the aetiology of complex, multifactorial diseases (4). An example is obesity, an increasingly pressing medical issue in developed countries. In congenital leptin disorder, a rare disease exhibiting an autosomal recessive inheritance pattern, severe obesity is a typical clinical feature. Affected individuals are unable to produce leptin because of mutations in the leptin encoding gene. Leptin acts on the hypothalamus to halt the production of neuropeptide Y, a neurotransmitter responsible for stimulating food, specifically carbohydrate, intake (6). Thus, studying congenital leptin disorder and other related Mendelian obesity disorders has helped scientists gain deeper insight into the complexity of the underlying causes behind obesity, one of which is the effects of leptin on the human body.

Another example is Van der Woude syndrome, an autosomal dominant condition caused by mutations in the IRF6 gene. It is characterised by a cleft lip and palate, hypodontia and lower lip pits (7). Interestingly, IRF6 mutations were also shown to be associated with non-syndromic isolated cleft lips and palates, which are complex traits and more prevalent in the general population than Van der Woude syndrome (8). This illustrates how the same defective gene could be responsible for rare inherited diseases and common medical conditions simultaneously. In essence, this shows Mendelian disorders and complex diseases that share overlapping phenotypes could be caused by the same sets of genetic aberrations (4).

Furthermore, systematic analyses using statistical methodologies have demonstrated that certain Mendelian disorders and complex diseases share a common genetic foundation. A study examining patients with concomitant Mendelian disorders and cancer revealed genetic connections between the two (9). The researchers’ initial hypothesis was that genetic mutations responsible for certain Mendelian disorders may predispose to the development of cancer. They found that genes associated with melanoma (MC1R and TYR), for instance, are also mutated in patients with oculocutaneous albinism, a Mendelian recessive disorder in which patients lack pigment in their skin, hair or eyes (10). Identifying cancer-driving genes that are found in Mendelian disorders enables scientists to understand the genetic basis of cancer development as well as various clinical presentations in cancer patients.

Although Mendel’s legacy has undoubtedly shaped our present understanding of inheritance, his discoveries alone cannot fully encapsulate the science behind complex diseases. The study of Mendelian disorders has given scientists a strong grounding for further research using advanced technologies such as whole genome sequencing and genome-wide association studies (11, 12), enhancing our knowledge of the genetic mechanisms and pathogenesis underlying polygenic diseases which would have been impossible in the 19th century.

• Molnar, Charles. Concepts Of Biology – 1st Canadian Edition. 1st ed., 2019, pp. Chapter 8.1.
• Chial, Heidi. “Gregor Mendel And Single-Gene Disorders | Learn Science At Scitable”. Scitable By Nature Education, 2008, https://www.nature.com/scitable/topicpage/mendelian-genetics-patterns-of-inheritance-and-single-966/.
• Miko, Ilona. “Gregor Mendel And The Principles Of Inheritance”. Scitable By Nature Education, 2008, https://p75fz1.nbcnews.top/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593.
• Reid, Jeremy. “Rare Disease Research Helps Us Understand Medicine For All Diseases – On Biology”. Biomed Central, 2016, https://blogs.biomedcentral.com/on-biology/2016/02/26/rare-disease-research-helps-understand-medicine-diseases/.
• Collins, Samuel et al. The Genetics Of Allergic Disease And Asthma. 4th ed., Elsevier, 2016, pp. 18-30, https://www.sciencedirect.com/science/article/pii/B9780323298759000033, Accessed 25 Feb 2022.
• Beck, B. “Neuropeptide Y In Normal Eating And In Genetic And Dietary-Induced Obesity”. Philosophical Transactions Of The Royal Society B: Biological Sciences, vol 361, no. 1471, 2006, pp. 1159-1185. The Royal Society, https://doi.org/10.1098/rstb.2006.1855. Accessed 25 Feb 2022.
• Chial, Heidi. “Human Genetic Disorders: Studying Single-Gene (Mendelian) Diseases | Learn Science At Scitable”. Nature.Com, 2008, https://www.nature.com/scitable/topicpage/rare-genetic-disorders-learning-about-genetic-disease-979/.
• Craig, Johanna. “Complex Diseases: Research And Applications”. Nature.Com, 2008, https://www.nature.com/scitable/topicpage/complex-diseases-research-and-applications-748/#:~:text=To%20comprehend%20the%20intricacies%20of,passed%20from%20generation%20to%20generation.
• Melamed, Rachel D. et al. “Genetic Similarity Between Cancers And Comorbid Mendelian Diseases Identifies Candidate Driver Genes”. Nature Communications, vol 6, no. 1, 2015. Springer Science And Business Media LLC, https://doi.org/10.1038/ncomms8033. Accessed 26 Feb 2022.
• “Oculocutaneous Albinism – NORD (National Organization For Rare Disorders)”. NORD (National Organization For Rare Disorders), https://rarediseases.org/rare-diseases/oculocutaneous-albinism/.
•  “Genome-Wide Association Studies Fact Sheet”. National Human Genome Research Institute, 2020, https://www.genome.gov/about-genomics/fact-sheets/Genome-Wide-Association-Studies-Fact-Sheet.
•  Benowitz, Steven. “Centers For Mendelian Genomics Uncovering The Genomic Basis Of Hundreds Of Rare Conditions”. National Human Genome Research Institute, 2015, https://www.genome.gov/news/news-release/Centers-for-Mendelian-Genomics-uncovering-the-genomic-basis-of-hundreds-of-rare-conditions.

  Hannah Wilson Raphael House Rudolf Steiner School Lower Hutt, New Zealand Teacher: Ms. Sarah McKenzie

From his study of pea plants, Gregor Mendel developed three fundamental principles of inheritance: the principle of uniformity, the principle of segregation, and the principle of independent assortment (1). All monogenic traits follow these principles and are thus called Mendelian traits (1,2). Therefore, Mendel’s principles can be used to study Mendelian diseases, notably through pedigree analysis (1,2). The study of Mendelian diseases can in turn provide valuable insight into complex (non-Mendelian) diseases due to genetic correlations between Mendelian and complex diseases (3-6).

Mendel’s principles enable us to both decipher the past inheritance and predict the future inheritance of Mendelian diseases through pedigree analysis. Pedigree charts are diagrams based on Mendel’s principles that visually represent a family’s inheritance history of a Mendelian trait (1,2). Analysis of pedigree charts reveals whether the allele responsible is dominant or recessive, autosomal or sex-linked, due to the specific inheritance pattern exhibited by each allele type (2). Autosomal recessive diseases such as phenylketonuria (PKU) and sickle cell anemia can skip generations because two heterozygous (carrier) parents can give rise to progeny with either the affected or wild-type phenotype (2). Autosomal dominant diseases never skip generations unless random mutation occurs (2). Conversely, sex-linked Mendelian diseases display unique inheritance patterns depending on whether the disease is X-linked or Y-linked, dominant or recessive (2).

Pedigree analysis is applied in genetic counselling (7). Genetic counsellors presented with the family history of two individuals can predict the probability of each possible genotype and phenotype occurring in future offspring (7). These probabilities equip individuals with the information they need to make an informed reproductive decision. Furthermore, the simplicity of Mendel’s principles makes them accessible to the general public, better enabling individuals to understand the nature of their or their loved one’s disease. Nowadays, fetuses can be screened for common genetic defects during pregnancy, however, pedigree analysis maintains its value in that it can provide preliminary information before conception (8).

Although Mendel’s principles form the foundation of inheritance, most human diseases are complex, meaning they violate Mendel’s principles of inheritance (3). Examples of complex diseases include schizophrenia, hypertension, multiple sclerosis, and Alzheimer’s disease (3). Complex diseases are polygenic, meaning they are influenced by multiple genes, and are subject to environmental influence (3). Some also exhibit pleiotropy and epistatic interactions (9,10). Thus, unlike Mendelian diseases, complex diseases lack distinct inheritance patterns (3,4). This poses a challenge to geneticists when attempting to predict an individual’s risk of developing a complex disease.

In addition, there is now evidence that Mendelian and complex diseases are more interconnected than scientists formerly believed (11). For example, cystic fibrosis, typically categorized as an autosomal recessive Mendelian disease, is now believed to involve multiple loci (5,6). A mutation in the CTFR gene, which codes for a membrane channel protein for chlorine ions, forms the primary genetic basis for cystic fibrosis (6,12). However, variation in the severity of cystic fibrosis has been linked to potential modifier genes separate from the CTFR gene (5,6). As eukaryotic gene expression involves transcription factors as well as the structural gene(s) underlying a trait, it is highly likely that other Mendelian diseases also have complex aspects (13).

The study of Mendelian diseases can directly inform the study of complex diseases when a Mendelian disease acts as a model for a complex disease. Such is the case for Van der Woude syndrome, a rare autosomal dominant Mendelian disorder caused by mutations in the IRF6 gene (3,14). Symptoms of Van der Woude syndrome include cleft lip, a birth defect where the tissue in the lip does not join up completely before birth (3,14). Statistical studies provide evidence that one of the genes responsible for isolated cleft lip, a complex disorder, is IRF6, the same gene underlying Van der Woude syndrome (3). The discovery of links between other phenotypically similar Mendelian and complex diseases would be highly beneficial when considering that complex diseases are simultaneously challenging to study in isolation and highly prevalent in the general population (3,4).

Mendel’s abstract but fundamental principles of inheritance have paved the way for modern genetics. These principles directly enable both scientists and the general public to comprehend the inheritance of Mendelian diseases (1). The study of Mendelian diseases can also inform our understanding of complex diseases, especially in cases where a complex disease shares an element of its genetic basis with a Mendelian disease (ref). Therefore, despite their rarity, humankind as a whole is certain to benefit from the continued study of Mendelian diseases.

• Miko, I. (2008). Gregor Mendel and the Principles of Inheritance. Nature Education. https://www.nature.com/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593/
• Chial, H. (2008). Mendelian Genetics: Patterns of Inheritance and Single-Gene Disorders. Nature Education. https://www.nature.com/scitable/topicpage/mendelian-genetics-patterns-of-inheritance-and-single-966/
• Craig, J. (2008). Complex Diseases: Research and Applications. Nature Education. https://www.nature.com/scitable/topicpage/complex-diseases-research-and-applications-748/
• MedlinePlus. (2021, May 14). What are complex or multifactorial disorders? https://medlineplus.gov/genetics/understanding/mutationsanddisorders/complexdisorders
• O’Neal, W. K., & Knowles, M. R. (2018). Cystic Fibrosis Disease Modifiers: Complex Genetics Defines the Phenotypic Diversity in a Monogenic Disease. Annual review of genomics and human genetics, 19, 201–222. https://doi.org/10.1146/annurev-genom-083117-021329
• Buschman, H. (2019, December 10). Modifier Gene May Explain Why Some with Cystic Fibrosis are Less Prone to Infection. UC San Diego Health. https://health.ucsd.edu/news/releases/Pages/2019-12-10-modifier-gene-may-explain-why-some-with-cystic-fibrosis-less-prone-to-infection.aspx
• NBIAcure. (2014). Genetic Counselling. http://nbiacure.org/learn/genetic-counseling/
• MedlinePlus. (2021, September 29). Prenatal Testing. https://medlineplus.gov/prenataltesting.html
• Nagel R. L. (2005). Epistasis and the genetics of human diseases. Comptes rendus biologies, 328(7), 606–615. https://doi.org/10.1016/j.crvi.2005.05.003
• Gratten, J. & Visscher, P.M. (2016). Genetic pleiotropy in complex traits and diseases: implications for genomic medicine. Genome Med 8, 78. https://doi.org/10.1186/s13073-016-0332-x
• Jin, W et al. (2012, April 1). A systematic characterization of genes underlying both complex and Mendelian diseases. Human Molecular Genetics, Volume 21, Issue 7, Pages 1611–1624. https://doi.org/10.1093/hmg/ddr599
• MedlinePlus. (2021, July 6). Cystic Fibrosis. https://medlineplus.gov/genetics/condition/cystic-fibrosis/#causes
• Urry, Meyers, N., Cain, M. L., Wasserman, S. A., Minorsky, P. V., & Reece, J. B. (2018). Campbell Biology: Australian and New Zealand Version (11th edition. Australian and New Zealand version.). Pearson Australia.
• Children’s Hospital of Philadelphia. (2022). Van der Woude Syndrome. https://www.chop.edu/conditions-diseases/van-der-woude-syndrome

Emma Youngblood St. John Paul the Great Catholic High School Dumfries, Virginia Teacher: Dr. Clare Kuisell

“I am convinced that it will not be long before the whole world acknowledges the results of my work.” Gregor Mendel published the results of his pea plant experiments in 1865, but it wasn’t until the 1900s that people began to rediscover his work, and even then, it was controversial (Williams & Rudge, 2015). Now, nearly 200 years later, he is known as the father of the science of genetics, and students throughout the world learn about the laws of segregation and independent assortment which originated from Mendel’s observations. Mendel’s discoveries allow us to understand Mendelian disorders because they have been used to identify patterns of inheritance, which can be applied to genes that are known to have influence in complex diseases.

Single gene diseases are often referred to as Mendelian diseases–or disorders–and may be inherited in one of several patterns (Genetic Alliance, 2010). An example of such a disease is Marfan syndrome. With an incidence of approximately 1 in 5000 individuals, Marfan syndrome is an autosomal dominant disease that affects the body’s connective tissue (Coelho & Almeida, 2020). Using Mendel’s law of dominance and uniformity, which differentiates dominant and recessive alleles (Lewis & Simpson, 2021), one can predict the inheritance pattern of Marfan syndrome using the same calculations and ratios Mendel discovered in his pea plants. Because the mutated allele of the gene is dominant, a child who inherits Marfan syndrome must have a parent who also has it. This also means that Marfan syndrome, like other autosomal dominant diseases, would occur in every generation until the dominant allele is not inherited from either the mother or the father. Mendel’s work has allowed the identification of different types of inheritance patterns of single gene disorders to be very simple.

Complex diseases, while much less predictable than Mendelian disorders, are still influenced by genetics. Almost all complex diseases are affected by multiple genes and environmental factors, and examples include heart disease, cancer, and diabetes (National Human Genome Research Institute, 2013). Another well-known complex disease is Alzheimer’s Diseases (AD). Approximately 44 million people currently live with AD, and that number is expected to triple by 2050 (Lane et al., 2018). Aside from age, one of the highest risk factors for AD is the presence of the ε4 allele of the gene that codes for apolipoprotein E, also called ApoE (Yin & Wang, 2018). Recent studies have also shown that two of the most reliable biomarkers for AD are Aβ protein deposits and phosphorylated tau proteins (Mantzavinos & Alexiou, 2017). By studying the genes that code for these proteins and the gene that codes for, scientists may be able to identify a better way to treat or even cure AD. The multiple factors that affect complex diseases make it nearly impossible to determine exact patterns of inheritance, but if single genes that influence them can be isolated, the same patterns used to predict inheritance patterns in Mendelian disorders can be used to predict a high or low likelihood of developing or inheriting a complex disease.

Mendel’s discoveries have been essential in determining the inheritance patterns of Mendelian disorders, which can also be used to form a more accurate prediction of the inheritance of complex diseases. Interest in genetics-related careers is rapidly growing; the U.S. Bureau of Labor Statistics shows a job outlook of 26% from 2020 to 2030. This compares to the outlook of 14% for other healthcare occupations and 8% for all occupations (2021). Increased interest in the field of genetics may lead to new ways of applying the discoveries Mendel made nearly 200 years ago to solve modern questions and problems. It might have taken longer for the world to acknowledge the results of his work than he believed it would, but there is no doubt that once it did, Gregor Mendel’s work opened a realm of new scientific possibilities that will certainly endure for 200 years more.

Boyle, E. A., Li, Y. I., & Pritchard, J. K. (2017). An Expanded View of Complex Traits: From Polygenic to Omnigenic. Cell, 169(7), 1177–1186. https://doi.org/10.1016/j.cell.2017.05.038 Coelho, S. G., & Almeida, A. G. (2020). Marfan syndrome revisited: From genetics to the clinic. Síndrome de Marfan revisitada – da genética à clínica. Revista portuguesa de cardiologia, 39(4), 215–226. https://doi.org/10.1016/j.repc.2019.09.008 Genetic Alliance. (2010, February 17). Classic Mendelian Genetics (Patterns of Inheritance). Understanding Genetics: A District of Columbia Guide for Patients and Health Professionals. Retrieved January 20, 2022, from https://www.ncbi.nlm.nih.gov/books/NBK132145/ Lane, C. A., Hardy, J., & Schott, J. M. (2018). Alzheimer’s disease. European journal of neurology, 25(1), 59–70. https://doi.org/10.1111/ene.13439 Lewis, R. G., & Simpson, B. (2021). Genetics, Autosomal Dominant. In StatPearls. StatPearls Publishing. Mantzavinos, V., & Alexiou, A. (2017). Biomarkers for Alzheimer’s Disease Diagnosis. Current Alzheimer research, 14(11), 1149–1154. https://doi.org/10.2174/1567205014666170203125942 National Human Genome Research Institute. (2013, May 3). Genetic Analysis Tools Help Define Nature and Nurture in Complex Disorders. Genome.gov. Retrieved January 20, 2022, from https://www.genome.gov/10000865/complex-disorders-background U.S. Bureau of Labor Statistics. (2021, September 8). Genetic counselors : Occupational outlook handbook. U.S. Bureau of Labor Statistics. Retrieved January 21, 2022, from https://www.bls.gov/ooh/healthcare/genetic-counselors.htm Williams, C. T., & Rudge, D. W. (2015). Mendel and the Nature of Science. The American Biology Teacher, 77(7), 492–499. https://doi.org/10.1525/abt.2015.77.7.3 Yin, Y., & Wang, Z. (2018). ApoE and Neurodegenerative Diseases in Aging. Advances in experimental medicine and biology, 1086, 77–92. https://doi.org/10.1007/978-981-13-1117-8_5

  Vivian Yuan Ridgewood High School Ridgewood, New Jersey Teacher: Mr. Ryan Van Treuren

Complex Diseases Through the Lens of Mendelian Genetics

In 2001, the Human Genome Project reported that the human genome contains 20,000 to 25,000 protein-coding genes (1, 2). Among those genes, less than 10% are related to single gene diseases, also known as monogenic or Mendelian disorders (2). With the recent advances of genome-wide association studies (GWAS) and single nucleotide polymorphism (SNP) sequencing approaches, interest in human genetics has shifted from rare Mendelian disorders to more common complex diseases, which involve both genetic components and environmental factors (2, 3, 4). Although Mendelian disorders affect a small portion of the population, studying them has contributed greatly to our understanding of genetic mutations and the risk factors underlying the aetiology of complex diseases.

The foundation of all modern human genetic studies relies upon Gregor Mendel’s study with pea plants. Through his experiments, Mendel discovered three laws: the law of dominance, the law of segregation, and the law of independent assortment (5, 6). Mendelian laws aptly dictate Mendelian disorders, which allows scientists to better determine the inheritance pattern of diseases. Disease inheritance genes can be classified as autosomal or sex linked, dominant or recessive. Huntington’s disease, a progressive neurodegenerative disorder, is an example of autosomal dominant Mendelian disorder, because only one copy of the defective gene from one parent is needed for disease manifestation. Conversely, phenylketonuria (PKU), which causes the accumulation of the amino acid phenylalanine, is an autosomal recessive disease. Both parents must give the defective gene to the child for the disease to appear. If only one parent carries the mutated gene, the child will not be affected, but they could still be a carrier of the mutated gene. Luckily, doctors are now able to predict the genotype and phenotype of an individual using pedigree analysis. Now, PKU could be confirmed within three days after birth, and PKU babies will be switched to a low protein and phenylalanine diet, preventing cognitive abnormality.

Although complex diseases do not follow Mendelian inheritance, the mechanisms learned from Mendelian diseases can help scientists understand complex diseases (2). Initially, cystic fibrosis was characterized as an autosomal recessive monogenic disease because of the mutations in the Cystic Fibrosis Trans-membrane conductance Regulator (CFTR) gene. However, recent studies showed that not all CFTR mutations produce the same disease, and disease severity is associated with modifier genes (7, 8). The interactions between modifier genes and different CFTR mutations heavily affect the phenotypic complexity and expressivity of CFTR genes. Due to the discovery of these modifier genes, cystic fibrosis is now classified as an oligogenic disease, involving a few genes. In a study of several families with epilepsy, multiple members carrying the same SCN1A gene mutations showed varying phenotypes and disease severity. Like the case in cystic fibrosis, modifier genes were also identified in epilepsy. While they may not be pathogenic, those genes still account for the variability in SCN1A-related phenotype (9).

In addition, study of Mendelian diseases can provide useful information about individual gene’s contribution to the phenotypes in complex diseases. When comparing two databases, Online Mendelian Inheritance in Man database (OMIM) and Genetic Association database (GAD), scientists found that among the 968 Mendelian genes identified, 524 genes are also genetic risk factors for complex diseases (3); hence, those genes are called complex-Mendelian genes (CM genes). CM genes were found to have higher allelic Odds Ratios (ORs) than genes associated only with complex disease, suggesting that CM genes have stronger effects on the complex phenotypes they affect (10).​ ​​​​​​

Furthermore, some complex diseases, such as breast cancer and hypertension, have Mendelian subtypes that clearly display the inheritance patterns typical of monogenic diseases. Hereditary breast cancer, accounting for 5%-10% of all breast cancer, is mainly caused by a mutation in BRCA1 and BRCA2 genes (11). The inheritance of BRCA1 and BRCA2 follows an autosomal dominant pattern, and carriers of those two genes are at higher risk of developing other cancers, especially ovarian cancer. Similarly, scientists have found that some types of hypertension, called monogenic hypertension, are caused by distinct genetic mutations resulting in gain-of-function or loss-of-function in the mineralocorticoid, glucocorticoid, or sympathetic pathways (12).

The knowledge gained from studying genetic inheritance is surely invaluable to understanding diseases and finding treatments. Future applications of these basic principles laid out by Mendel over 150 years ago will lead doctors to predict disease manifestation and severity, working towards prevention and early treatment for all diseases, simple or complex.

• International Human Genome Sequencing Consortium (2004) Finishing the Euchromatic Sequence of the Human Genome. Nature 431: 931-945
• Antonarakis S.E. and Beckman J.S. (2006) Mendelian disorders deserve more attention. Nature Reviews Genetics 7: 277-282
• Jin WF, Qin PF, Lou HY and Xu SF. (2012) A systematic characterization of genes underlying both complex and Mendelian diseases. Human Molecular Genetics 21 (7): 1611-1624
• Craig J. (2018) Complex Diseases: Research and Applications. Nature Education 1 (1): 184 https://www.nature.com/scitable/topicpage/complex-diseases-research-and-applications-748/
• Miko I. (2008) Gregor Mendel and the Principles of Inheritance. Nature Education 1 (1): 134. https://www.nature.com/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593/
• Chial H. (2008) Mendelian Genetics: Patterns of Inheritance and Single-Gene Disorders. Nature Education 1 (1): 63. https://www.nature.com/scitable/topicpage/mendelian-genetics-patterns-of-inheritance-and-single-966/
• Buratti E., Brindisi A., Pagani,F. & Baralle F. E. Nuclear factor TDP-43 binds to the polymorphic TG repeats in CFTR intron 8 and causes skipping of exon 9: a functional link with disease penetrance. Am. J. Hum. Genet. 74, 1322–1325 (2004).
• O’Neal W.K. and Knowles M.R. Cystic Fibrosis Disease Modifiers: Complex Genetics Defines the Phenotypic Diversity in a Monogenic Disease. Annu. Rev. Genom. Hum. Genet. 2018. 19:201–22
• de Lange I.M., Mulder F., Slot R, et al (2020). Modifier genes in SCN1A-related epilepsy syndromes. Mol Genet Genomic Med. 8: e1103
• Spataro N., Rodriguez J., Navarro A., Bosch, E. (2017) Properties of Human Disease Genes and the Role of Genes Linked to Mendelian Disorders in Complex Disease Aetiology. Human Molecular Genetics 26 (3): 489-500
• Mehrgou A. and Akouchekian M. (2016) The Importance of BRCA1 and BRCA2 gene mutations in breast cancer development. Med J Islam Repub Iran 30: 369
• Raina R, Krishnappa V, Das A, et al (2019) Overview of Monogenic or Mendelian forms of Hypertension. Frontiers in Pediatrics 7: 263

Xinyi Zhang South Brunswick High School Monmouth Junction, New Jersey Teacher: Ms. Jessica Pagone

Genetic mutations lend each person their individuality, but certain variations can cause adverse health effects. Mendelian, or monogenic, disorders arise from variations in just one of the over 4,000 protein-coding genes that are currently associated with these diseases (2). Using Mendel’s principles to trace the inheritance pattern and phenotypes of a specific genetic mutation forms the basis of studying monogenic disorders. In turn, these findings can elucidate the role of various genetic mutations in diseases with more complex causes (8).

Gregor Mendel’s laws of genetic inheritance establish the framework for Mendelian patterns of inheritance. Given that each parent provides an allele for every gene in their offspring, if one parent has a genetic mutation that may cause a certain monogenic disorder, their offspring may inherit the mutant allele (5). Whether the child will develop the disorder or be a carrier depends on the dominance of the alleles they inherit (11).

Coupling Mendel’s principles with pedigree analysis reveal predictable modes of inheritance that bring light to the genetic nature of Mendelian diseases (5). Consider, for example, the realization of the inheritance pattern of sickle cell disease (SCD). Both parents need to have at least one mutant allele in the hemoglobin beta (HBB) gene to produce offspring with SCD (6). However, if their offspring only has one mutant allele, they will not be afflicted with SCD (6). With these observations, scientists determined that SCD is an autosomal recessive disorder in which it could only develop in people with two mutant alleles of the HBB gene (11). The inheritance pattern of a Mendelian disease would be different in an autosomal dominant disorder, where one mutant allele is enough to cause the disease, or in a sex-linked disorder, where diseases are inherited through the X or Y chromosome (11). Using Mendel’s principles to identify Mendelian inheritance patterns often serves as the first step in assessing disease risk and pinpointing the responsible genotype.

In actuality, Mendelian disorders are much rarer than complex disorders, which are distinguished from monogenic conditions because many genes, environmental interactions, and lifestyle choices all contribute to disease development (8). These variables complicate the determination of inheritance patterns or causative factors of a complex disease.

Despite their inherent differences, some connections have been uncovered between Mendelian and complex diseases. Many monogenic diseases are comorbid with complex ones (4). Furthermore, over 20% of the gene variations that cause Mendelian disorders have been implicated in at least one complex disorder (8). For instance, mutations in the IRF6 gene can lead to Van der Woude syndrome, a rare Mendelian disorder that causes cleft lip, cleft palate, and other facial deformities (10). Intriguingly, IRF6 mutations have also been implicated in complex, isolated forms of cleft lip and palate (12). These overlaps highlight the importance of utilizing Mendelian diseases to understand complex disease etiology.

Techniques such as whole-exome sequencing can link the characteristics of a Mendelian disease with the mutant gene that causes them (9). These findings are recorded in the Online Mendelian Inheritance in Man (OMIM), an accessible catalog of thousands of genotype-phenotype links for monogenic disorders (3). Studying this data has led to the identification of mutations and pathways that play a role in producing similar phenotypes in complex diseases (3,4). To better understand the complexity of essential hypertension, researchers studied many Mendelian disorders that are associated with high blood pressure, such as Liddle’s syndrome (7). Many of these disorders are caused by genetic mutations that alter proteins involved in renal salt balance (7). These studies brought attention to the importance of the kidneys and adrenal glands in regulating blood pressure and revealed the genetic mutations that may be associated with essential hypertension (7). Better knowledge of the molecular pathways behind essential hypertension has opened up new targets in drug development, such as ROMK, a renal potassium channel that is altered by a monogenic disorder known as Bartter syndrome type II (1).

Overall, while insights gleaned from studying Mendelian disorders cannot account for the environmental or lifestyle risks that contribute to complex diseases, they can guide research on pinpointing the pathophysiological processes and susceptibility alleles that bring about complex disorders. Thus, despite the rarity of Mendelian disorders, research on them should not be undercut to prioritize the study of prevalent complex diseases. A more comprehensive understanding of Mendelian disorders allows for more efficient risk assessment, prevention measures, and diagnoses for Mendelian and complex diseases alike, rendering it a valuable tool that should be further explored in the field of medical genetics.

• Abdel-Magid, A. F. (2016, November 22). Potential of renal outer medullary potassium (ROMK) channel as treatments for hypertension and heart failure. American Chemical Society. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5238487/
• Antonarakis, S. E. (2021, June 23). History of the methodology of disease gene identification … Wiley Online Library. Retrieved from https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.62400
• Brownlee, C. (n.d.). OMIM turns 50: A genetic database’s past, present, and future. Johns Hopkins Medicine. Retrieved from https://www.hopkinsmedicine.org/research/advancements-in-research/fundamentals/in-depth/omim-turns-50-a-genetic-databases-past-present-and-future
• Kumar Freund, M. (2018, October 4). Phenotype-Specific Enrichment of Mendelian Disorder Genes near GWAS Regions across 62 Complex Traits. Cell. Retrieved from https://www.cell.com/ajhg/fulltext/S0002-9297(18)30285-4
• Lewis, R. G. (2021, May 7). Genetics, autosomal dominant. StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK557512/
• Mangla, A. (2021, December 19). Sickle cell anemia. StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK482164/
• Seidel, E., Scholl, U. I. (2017, November 1). Genetic mechanisms of human hypertension and their implications for blood pressure physiology. Physiological Genomics. Retrieved from https://journals.physiology.org/doi/full/10.1152/physiolgenomics.00032.2017
• Spataro, N., Rodríguez, J. A., Navarro, A., & Bosch, E. (2017, February 1). Properties of human disease genes and the role of genes linked to mendelian disorders in complex disease aetiology. Human molecular genetics. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409085/
• Suwinski, P., Ong, C. K., Ling, M. H. T., Poh, Y. M., Khan, A. M., & Ong, H. S. (2019, February 12). Advancing personalized medicine through the application of whole exome sequencing and Big Data Analytics. Frontiers. Retrieved from https://www.frontiersin.org/articles/10.3389/fgene.2019.00049/full
• U.S. National Library of Medicine. (2020, August 18). Van der Woude Syndrome: Medlineplus Genetics. MedlinePlus. Retrieved from https://medlineplus.gov/genetics/condition/van-der-woude-syndrome/
• 11. U.S. National Library of Medicine. (2021, April 19). What are the different ways a genetic condition can be inherited?: Medlineplus Genetics. MedlinePlus. Retrieved from https://medlineplus.gov/genetics/understanding/inheritance/inheritancepatterns/
• Zhao, H., Zhang, M., Zhong, W., Zhang, J., Huang, W., Zhang, Y., Li, W., Jia, P., Zhang, T., Liu, Z., Lin, J., & Chen, F. (2018, July 20). A novel IRF6 mutation causing non-syndromic cleft lip with or without cleft palate in a pedigree. OUP Academic. Retrieved from https://academic.oup.com/mutage/article/33/3/195/5056500

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• Biology Article
• Dna Structure

DNA: Structure, Function and Discovery

Nucleic acids are the organic materials present in all organisms in the form of DNA or RNA. These nucleic acids are formed by the combination of nitrogenous bases, sugar molecules and phosphate groups that are linked by different bonds in a series of sequences. The DNA structure defines the basic genetic makeup of our body. In fact, it defines the genetic makeup of nearly all life on earth.

Table of Contents

What is DNA?

Dna structure, chargaff’s rule, dna replication.

• Function of DNA

Why DNA is called a Polynucleotide Molecule?

Read on to explore DNA meaning, structure, function, DNA discovery and diagram in complete detail.

“DNA is a group of molecules that is responsible for carrying and transmitting the hereditary materials or the genetic instructions from parents to offsprings.”

This is also true for viruses, as most of these entities have either RNA or DNA as their genetic material . For instance, some viruses may have RNA as their genetic material, while others have DNA as the genetic material. The Human Immunodeficiency Virus (HIV) contains RNA, which is then converted into DNA after attaching itself to the host cell.

Apart from being responsible for the inheritance of genetic information in all living beings, DNA also plays a crucial role in the production of proteins. Nuclear DNA is the DNA contained within the nucleus of every cell in a eukaryotic organism. It codes for the majority of the organism’s genomes while the mitochondrial DNA and plastid DNA handles the rest.

The DNA present in the mitochondria of the cell is termed mitochondrial DNA. It is inherited from the mother to the child. In humans, there are approximately 16,000 base pairs of mitochondrial DNA. Similarly, plastids have their own DNA, and they play an essential role in photosynthesis.

Also Read:  Difference between gene and DNA

Full-Form of DNA

DNA is known as Deoxyribonucleic Acid. It  is an organic compound that has a unique molecular structure. It is found in all prokaryotic cells and eukaryotic cells . 

There are three different DNA types:

• A-DNA:  It is a right-handed double helix similar to the B-DNA form. Dehydrated DNA takes an A form that protects the DNA during extreme conditions such as desiccation. Protein binding also removes the solvent from DNA, and the DNA takes an A form.
• B-DNA:  This is the most common DNA conformation and is a right-handed helix. The majority of DNA has a B type conformation under normal physiological conditions.
• Z-DNA:  Z-DNA is a left-handed DNA where the double helix winds to the left in a zig-zag pattern. It was discovered by Andres Wang and Alexander Rich. It is found ahead of the start site of a gene and hence, is believed to play some role in gene regulation.

Who Discovered DNA?

DNA was first recognized and identified by the Swiss biologist  Johannes Friedrich Miescher in 1869 during his research on white blood cells .

The double helix structure of a DNA molecule was later discovered through the experimental data by James Watson and Francis Crick. Finally, it was proved that DNA is responsible for storing genetic information in living organisms.

Also Read:  Difference between deoxyribose and ribose

DNA Diagram

The following diagram explains the DNA structure representing the different parts of the DNA. DNA comprises a sugar-phosphate backbone and the nucleotide bases (guanine, cytosine, adenine and thymine).

DNA Diagram representing the DNA Structure

Read more: Properties of DNA

The DNA structure can be thought of as a twisted ladder. This structure is described as a double-helix, as illustrated in the figure above. It is a nucleic acid, and all nucleic acids are made up of nucleotides.  The DNA molecule is composed of units called nucleotides, and each nucleotide is composed of three different components such as sugar, phosphate groups and nitrogen bases. 

The basic building blocks of DNA are nucleotides, which are composed of a sugar group, a phosphate group, and a nitrogen base. The sugar and phosphate groups link the nucleotides together to form each strand of DNA. Adenine (A), Thymine (T), Guanine (G)  and Cytosine (C) are four types of nitrogen bases.

These 4 Nitrogenous bases pair together in the following way: A  with  T, and C  with G . These base pairs are essential for the DNA’s double helix structure, which resembles a twisted ladder.

The order of the nitrogenous bases determines the genetic code or the DNA’s instructions.

Components of DNA Structure

Among the three components of DNA structure, sugar is the one which forms the backbone of the DNA molecule. It is also called deoxyribose. The nitrogenous bases of the opposite strands form hydrogen bonds, forming a ladder-like structure.

DNA Structure Backbone

The DNA molecule consists of 4 nitrogen bases, namely adenine (A), thymine (T), cytosine (C) and Guanine (G), which ultimately form the structure of a nucleotide. The A and G are purines, and the C and T are pyrimidines.

The two strands of DNA run in opposite directions. These strands are held together by the hydrogen bond that is present between the two complementary bases. The strands are helically twisted, where each strand forms a right-handed coil, and ten nucleotides make up a single turn.

The pitch of each helix is 3.4 nm. Hence, the distance between two consecutive base pairs (i.e., hydrogen-bonded bases of the opposite strands) is 0.34 nm.

The DNA coils up, forming chromosomes , and each chromosome has a single molecule of DNA in it. Overall, human beings have around twenty-three pairs of chromosomes in the nucleus of cells. DNA also plays an essential role in the process of cell division.

Also Read:   DNA Packaging

Recommended Video:

Erwin Chargaff , a biochemist, discovered that the number of nitrogenous bases in the DNA  was present in equal quantities. The amount of A is equal to T, whereas the amount of C is equal to G.

In other words, the DNA of any cell from any organism should have a 1:1 ratio of purine and pyrimidine bases.

DNA replication is an important process that occurs during cell division. It is also known as semi-conservative replication, during which DNA makes a copy of itself.

DNA replication takes place in three stages:

Step 1: Initiation

The replication of DNA begins at a point known as the origin of replication. The two DNA strands are separated by the DNA helicase. This forms the replication fork.

Step 2: Elongation

DNA polymerase III reads the nucleotides on the template strand and makes a new strand by adding complementary nucleotides one after the other. For eg., if it reads an Adenine on the template strand, it will add a Thymine on the complementary strand.

While adding nucleotides to the lagging strand, gaps are formed between the strands. These gaps are known as Okazaki fragments. These gaps or nicks are sealed by ligase.

Step 3: Termination

The termination sequence present opposite to the origin of replication terminates the replication process. The TUS protein (terminus utilization substance) binds to terminator sequence and halts DNA polymerase movement. It induces termination.

Also Read:  DNA Replication

DNA Function

DNA is the genetic material which car­ries all the hereditary information. Genes are the small segments of DNA, consisting mostly of 250 – 2 million base pairs. A gene code for a polypeptide molecule, where three nitrogenous bases sequence stands for one amino acid.

Polypeptide chains are further folded in secondary, tertiary and quaternary structures to form different proteins. As every organism contains many genes in its DNA, different types of proteins can be formed. Proteins are the main functional and structural molecules in most organisms. Apart from storing genetic information, DNA is involved in:

• Replication process: Transferring the genetic information from one cell to its daughters and from one generation to the next and equal distribution of DNA during the cell division
• Mutations: The changes which occur in the DNA sequences
• Transcription
• Cellular Metabolism
• DNA Fingerprinting
• Gene Therapy

Also Read:  r-factor

The DNA is called a polynucleotide because the DNA molecule is composed of nucleotides – deoxyadenylate (A) deoxyguanylate (G) deoxycytidylate (C)  and deoxythymidylate (T), which are combined to create long chains called a polynucleotide. As per the DNA structure, the DNA consists of two chains of polynucleotides.

Also Read:  Genetic Material

For more detailed information on DNA meaning, diagram, its types, DNA structure and function, or any other related topics, explore at  BYJU’S Biology.

Explore more

• Difference between Replication and Transcription
• DNA Cloning
• DNA As Genetic Material
• DNA Structure and Polynucleotide
• How is DNA inherited from each parent?
• Do you get more DNA from your mother or father?

Frequently Asked Questions

What is the structure of dna.

DNA is a double helical structure composed of nucleotides. The two helices are joined together by hydrogen bonds. The DNA also bears a sugar-phosphate backbone.

What are the three different types of DNA?

The three different types of DNA include:

How is Z-DNA different from other forms of DNA?

Z-DNA is a left-handed double helix. The helix winds to the left in a zig-zag manner. On the contrary, A and B-DNA are right-handed DNA.

What are the functions of DNA?

The functions of DNA include:

• Replication
• Gene expression

What type of DNA is found in humans?

B-DNA is found in humans. It is a right-handed double-helical structure.

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163 DNA Essay Topic Ideas & Examples

🏆 best dna topic ideas & essay examples, 💡 most interesting dna argumentative essay topics, 📑 good research topics about dna, 📌 simple & easy dna essay titles, 👍 good essay topics on dna, ❓ questions about dna.

• Moral and Ethical Issues of Recombinant DNA Technology In my opinion that debate is of the greatest importance and my hope is that these six lectures may have contributed to it.
• Ethics of Informed Consent in DNA Research The ethical issue that is the focus of the current study is the use of patient DNA for research by a company without their knowledge and consent.
• Forensic DNA Analysis: A Technique to Achieve a Conclusion of Identity Thus, a DNA match corroborates the fact that the suspect was at the scene of the crime and this evidence can help in establishing a case against the suspects.
• The Main Objective of DNA Fingerprinting in Agriculture Therefore, the main objective of DNA fingerprinting in agriculture is to overcome the limitation of insufficient dissimilarity among prior genotypes and come up with the best ideas to discover new molecular markers and collect data […]
• DNA Replication as a Semiconservative Process The process of DNA replication has been studied extensively as the pathway to understanding the processes of inheritance and the possible platform for addressing a range of health issues occurring as a result of DNA […]
• The Amplification of DNA Samples The isothermal amplification of nucleic acids represents a simplified process that allows for the quick and efficient accumulation of nucleic acid sequences in an environment of constant temperatures.
• Application of DNA in Criminal Forensics In phylogenetic studies, the analysis of DNA from fossil remains allows one to determine the taxonomic identity of a species, while in forensics, one can find the connection between traces and the perpetrator or the […]
• Rosalind Franklin: The Discovery of the DNA Structure The discovery of the spatial structure of DNA undoubtedly made a decisive contribution to the development of modern biological science and related fields.
• Neanderthal DNA in the Genomes The article shares the reasons behind the presence of Denisovans; genetic fingerprints are present in many parts of the world today.
• The Nature of DNA Structure Discovery Thus, scientists should expand the idea about the nature of discovery without relying only on insight or results, acknowledging Franklin as a discoverer of DNA structure. It is time to reconsider the nature of discovery […]
• The Discovery of the Deoxyribonucleic Acid (DNA) Structure Watson and Crick are independent; they come up with the idea of building a DNA structure on their own. Chadarevien argues that the image of Crick, Watson, and the double-helical DNA model has a great […]
• Transfer of Beta-Carotene via DNA Techniques Adding yeast as a vector may significantly alleviate the incorporation of the new genes into any species because it includes protein which is vital for the species’ growth and rapid gene manipulation.
• DNA Sequencing with Polymerase Chain Reaction Sixteen possible combinations of the four nucleotide bases of the DNA would give rise to the 16 amino acids. This explains the high melting point of a high G + C content DNA.
• Mitochondria DNA (mtDNA) in Genealogy It is the development of mtDNA that enabled Sykes to trace and guess about the lives of the clan mothers since through it he was able to assess the genetic makeup of modern Europeans.
• DNA Evidence: The Case of the Golden State Killer Thus, DNA evidence should be used to narrow the circle of suspects before the technology is improved and other people could safely submit their DNA samples.
• DNA Analysis in Criminal Cases The murderer, Bradley Robert Edwards, was recognized to be guilty after committing two rapes in 2016 his DNA samples were taken from under the nails of the victim as she was fighting the rapist in […]
• Sex and Biology of Gender, From DNA to the Brain The video helped me actualize my prior knowledge on sex and gender as well as enriched my understanding of what biological processes make people transgender. In conclusion, the video under analysis helped me improve my […]
• DNA Cloning and Sequencing: The Experiment The plasmid vector pTTQ18 and the GFP PCR product will be digested with restriction enzymes and the desired DNA fragments obtained thereof will be purified by Polyacrylamide gel electrophoresis and ligated with DNA ligase resulting […]
• DNA Profiling and Required Genetic Testing The reliable tests for conducting genetic testing should be more than one in order to remove the element of doubt on matching DNA bands.
• DNA Microarray Technology and Applications These DNA microarrays are used by scientists in order to determine the appearance levels of a big number of genes, and also to the manifold region of a genome.
• Covalent Modification of Deoxyribonucleic Acid Regulates Memory Formation The article by Miller and Sweatt examines the possible role of DNA methylation as an epigenetic mechanism in the regulation of memory in the adult central nervous system.
• Short Tandem Repeat (STR) DNA Analysis and the CODIS Database The core STR loci developed provides a foundation for global databases of DNA and has future implications in the field of forensic science.
• DNA Barcoding Sequence Analysis of Unknown Plant The efficiency of this instrumental method is built on the idea of close similarity in the structure of DNA molecules to be more precise, the arrangement of nucleotides in it between closely related species: the […]
• DNA Analysis in Criminal Investigations DNA analysis is a method aimed at the identification of a person according to his or her characteristics of DNA. In the earlier stages of an investigation, when the mentioned technique serves as a powerful […]
• Ethical Issues on DNA Testing On some occasions, parents and clinicians have used such knowledge to manipulate the fetus’s genetic structure, hindering natural reproduction and messing with God’s creation.
• Importance of Deoxyribonucleic Acid The history of the discovery of DNA dates back to 1865 when Gregory Mendel used theories of heredity in analyzing the genetic profiles of pea plants.
• Knowing One’s DNA Genetic Makeup: Pros and Cons In addition, the knowledge that one might not get a job or insurance because of their genetic makeup is stressful and depressive.
• The Concept of DNA Barcoding The first step towards safeguarding and gaining from biodiversity involves sampling, identifying, and studying the biological specimens to identify the extent of the diversity and use that knowledge for the benefit of the country.
• Forensic Analysis of DNA and Biological Material This was the first stage when carrying out the DNA test on a biological material. Notably, the forensic analyst was not allowed to touch the collection pad of the swab as a precaution measure.
• Biochemical Metabolism: Foreign DNA Molecule The virtual gel should show the band pattern that would result from incubating the plasmid with restriction enzymes as indicated below.
• Developmental Biology: DNA and MicroRNA This is augmented by the strengthening of patterns and the increase in the number of lateral cells that are crucial for the process to be successful.
• Deoxyribonucleic Acid: Review The goals of this experiment are: to enable us to become well acquainted with the physical characteristics of DNA by separating it from living tissue, and the use of each stage in the isolation process […]
• Interesting and Relevant Applications of DNA Technology Week One Activities Learning Outcomes DNA Technology in Laboratory Medicine Diagnostic Relevance and future prospects. Interesting and Relevant Applications of DNA Technology Areas Most striking and need further review in my career – modernized to detect pathogens from the clinical samples in the diagnostic hospitals. Preferred method of identifying organisms based on genomic make up. […]
• DNA Retention and National Security The experiences of Kuwait and the UAE are yet to demonstrate the consequences of the extreme expansion of DNA retention system, but another country has also provided some information for the consideration in the worldwide […]
• Deoxyribonucleic Acid Profiling in Forensics The last part of the analysis includes discussion of the potential for error in DNA profiling. It has to do with the fact that DNA is a material that fulfills most of the criteria making […]
• DNA Tests in the O.J. Simpson’s Case The fact that John’s DNA results match the crime blood DNA results does not prove beyond reasonable doubt that he is responsible for Sally’s murder.
• The E.Z.N.A Commercial Kit: Soil DNA Extraction Optimisation In this paper, the researcher sought to investigate the effectiveness of using the kit for the purposes of optimising the extraction of DNA from marine soils.
• The Helical Structure of DNA: Watson and Crick’s Opinion In addition, the author of this paper makes a comparison between the structure proposed by the two biologists and the information provided in recent textbooks.
• Restriction of Lambda DNA in the Laboratory The DNA in the head of the virus has a unique structure. The restriction site is used for the purposes of recognizing a particular DNA molecule.
• DNA Vaccines: Optimization Methods The three optimization methods scientists have been using to optimize DNA vaccines are the use of regulatory elements, optimization of the codons, and addition of the kozak sequences.
• Comparative Sequence Study in Human and Primate DNA Samples In general, the differences between DNA samples are qualitative and quantitative, and this is explained by the fact that these are responsible for the key biological differences between humans and primates.
• Molecular Components of the DNA Molecule The DNA serves as storage of the genetic information in the form of codes. The DNA polymerase is the enzyme that is responsible for the combination of the phosphate and the nucleotide.
• FRET Detection or DNA Molecules It is for this reason that the method is possibly applicable in the DNA sequencing methods that are composed of single molecules and these are viewed as belonging to the “next-generation”.
• The DNA Extraction Procedure: Scientific Experiment It touches on plant cell DNA extraction, animal cell DNA extraction, sequence used in DNA extraction and composition of the sample.
• The Concept of DNA Cloning In the approach based on cells both the replicating molecule or the biological vehicle known as the vector and the foreign DNA fragment are cut using the same restriction enzyme to produce compatible cohesive or […]
• Biotechnology, Nanotechnology Its a Science for Brighter Future, DNA This means that there should be efforts that are aimed at the promotion of this field so that we can be in a position of solving most of these problems.
• Post Conviction DNA Testing The DNA was first presented as evidence in court in the year 1986 in the USA, and in the subsequent years it presented serious challenges in the court rooms, presently it is been accepted in […]
• Deoxyribonucleic Acid (DNA) Explained to Students In the chromosomes, DNA is organized and compacted by chromatin proteins. The interaction of DNA and other proteins is guided by compact structures.
• DNA Fingerprinting as Biotechnology Application DNA fingerprinting, also known as genetic fingerprinting or DNA profiling is a method used to identify a specific individual. DNA fingerprinting is used to determine the parents of a person i.e.establish paternity.
• Deoxyribonucleic Acid (DNA) Nanotechnology: Chemical and Physical Structure and Properties The essence of DNA in every living organism and certain viruses is that it forms the basis of the genetic instructions that are essential in the development and functioning of these organisms.
• Use of the Information Technology to Solve Crimes: DNA Tests and Biometrics The modus operandi of the IAFIS is as follows: The fingerprints are taken after arrest, processed locally, and then electronically transmitted to state or federal agencies for processing.”The fingerprints are then electronically forwarded through the […]
• Criminal Justice and DNA: “Genetic Fingerprinting” DNA is one of the popular methods used by criminologists today, DNA technique is also known as “genetic fingerprinting”.the name given the procedure by Cellmark Diagnostics, a Maryland company that certified the technique used in […]
• Structure of Deoxyribonucleic Acid The nucleotides join to one another by covalent bonds between the sugar of one nucleotide and the phosphate of the next. The sequence of nucleotides in the DNA strand can be different and vary in […]
• The Innocence Project, Habib Wahir’s Case: DNA Testing During the appeal, the court found that the semen left in the lady by the culprit did not match Habib’s DNA.
• DNA and Genealogy Solving Cold Case Murders: The Modern Technology The issues above are essential, and they make people ask questions of whether it is reasonable to use modern technology in DNA and genealogy.
• Modern Technology in DNA and Genealogy Solving Cold Case Murders The purpose of the study lays in establishing the relationship between ethical, legal, and privacy challenges of using genomics during the investigation.
• Benefits and Challenges of DNA Profiling The simplest option is to take a sample from the suspect and compare it with the DNA found at the crime scene.
• DNA and Evolution – What’s Similar Transformation, in molecular genetics, is a change in the hereditary properties of cells as a result of the penetration of foreign DNA into them.
• Importance of Expanding FBI’s Forensic DNA Laboratory In addition, acceptance of DNA analysis results as evidence in the Court of law has entrenched DNA analysis in forensic investigations. These have increased the number of samples for DNA analysis in FBI forensic laboratories.
• Biotechnology: Copying DNA (Deoxyribonucleic Acid) It refers to a new but identical collection of cells acquired from an original cell by the process of fission, wherein a cell divides itself forming two cells, or by the process of mitosis, wherein […]
• DNA in Criminal Investigations In fact, it is possible to speak about the advent of a new field of criminalistics, DNA profiling. RFLP analysis is very discriminative, though, it is worth mentioning, that the samples have to be undamaged, […]
• Deoxyribonucleic Acid (DNA): Structure & Function The significant factor was that the two strands run in the reverse directions and the molecule had a definite base pairing.
• Oswald T. Avery and the Discovery of the DNA Oswald Avery was a man driven with the desire to contribute to humanity but when he finally discovered something of utmost importance the world of science was not quick enough to give recognition to his […]
• Infectious Bacterial Identification From DNA Sequencing The first is the preparation of the DNA sequence and matching it with the database of known DNA sequences. Given below is a screenshot of the process PCR Amplification: To prepare the polymerase chain reaction, […]
• Mattew Warren: Four New DNA Letters Double Life’s Alphabet In this article, the author describes the work of Steven Benner and other scientists who contributed to the improvement in understanding the nature of synthetic DNA bases.
• DNA Testing Techniques and Challenges Therefore, even though the major part of the evidence can be inaccessible, the sample can be amplified due to the development of technology. The final stage is the evaluation of the accuracy of the analysis […]
• DNA Profiling and Analysis Interpretation Regarding the case of the robbery and murder of a man and a woman, different types of physical evidence can be collected. However, this method can be less effective in case of the contamination of […]
• Sleep Helps to Repair Damaged DNA in Neurons The researchers found that the chromosomes in the fish’s neurons would often change shape while their owners slept, enabling the repair of the damage accumulated in periods of activity.
• Dr. Michio Kaku’s Predictions of the DNA Screening In the documentary, the city planners warn the public that the insufficient growth and the development of the suburban areas threaten both the economy of the country as well as its community.
• Exponentials and Logarithms: the Cell and DNA The result will be; log to the base of 2 of ‘x’ equals ‘y’.’y’ usually refers to the power to which one raises ‘2’ to get ‘x’ This can be simplified as follows; F =2x […]
• Bird DNA Extraction: Sex Determination of Gallus Gallus DNA was obtained from blood, muscle tissue and feathers of the bird. The last step was to visualize the DNA extract through gel electrophoresis and making conclusions of the bird’s sex.
• Recombinant DNA Technology and pGLO Plasmid Use Transformation of bacterial cells, which is one of the approaches used in genetic engineering, involves the transfer of genetic material from one bacterium to another using a plasmid vector.
• DNA in Action: Sockeye Salmon Fisheries Management The researchers in the article carried out an analysis entailing a total sum of 9300 salmon fish species. The latter was followed by mixed stock samples in the lower region of Fraser River and test […]
• DNA-Binding Specificities of Human Transcription Factors The main purpose of the experiment was to analyze and determine how human transcription factors are specifically bound by DNA. Most human transcriptional factors have been systematically analyzed in the methodology and result sections of […]
• Innovator’s DNA: Entrepreneurial Assessment With time, I discovered that the questioning spirit was a reflection of what goes on in the mind of an entrepreneur.
• DNA Evidence and Its Use in the US Criminal Law The concluding statement of the Supreme Court of the United States defined the procedure of obtaining DNA samples as a procedure identical to taking fingerprints or taking pictures of the crime scene.
• Wildlife Forensic DNA Laboratory and Its Risks The mission of the Wildlife Forensic DNA Laboratory is to provide evidence to governmental and non-governmental organizations to ensure the protection of the wildlife in the country.
• Genes, Deoxyribonucleic Acid (DNA), and Heredity Others said RNA and DNA are the same and that they are responsible for making proteins. The statement “you are your genes” is virtually right because DNA is the basis of heredity and it is […]
• How Has DNA Changed the Field of Physical Anthropology? It is indeed correct to argue that contemporary DNA research has not only changed the field of physical anthropology in major ways, but it continues to alter and broaden our understanding and perceptions in a […]
• Organizational DNA Analysis Moreover, due to the spontaneous growth of the organization that took a snowball design, it experienced a challenge in supplying its products to the target consumers.
• DNA as an Evidence From a Crime Scene The mitochondrial DNA is transferred directly from the mother to the offspring and in this case, there is no DNA of the father present here.
• DNA Definition and Its Use by the US Police The location for most DNA is the nucleus though some may be found in the mitochondria and is called mitochondrial DNA.
• DNA Analysis: A Crime-Fighting Tool or Invasion of Privacy? This paper set out to demonstrate that DNA analysis offers a versatile tool for fighting crime and therefore ensuring the success of our civilization.
• The DNA of an Entrepreneur: Is There an Entrepreneur Gene
• The Use and Importance of DNA Profiling in the Police Force in America
• The Role of DNA Technology in Crime Investigation
• The Future of Computers and DNA Computing
• Will a National DNA Database Decrease Crime in the U.S
• The Human Genome Project and Patenting DNA
• The Essential Features of the Watson-Crick Model on the DNA
• The Structure of the DNA and the Future of Genetic Engineering
• The Effectiveness of DNA Evidence in Obtaining Criminal Convictions
• The Evolution of DNA Silencing Technology over the Years
• The History, Function and Advancement in DNA Technologies
• The Different Uses and Importance of DNA Replication
• The Advancement of DNA Testing in Criminal Trials and Its Benefits
• The Idea of Cloning Animals and Humans since the Discovery of DNA
• The Biochemical Description of the DNA and Its Importance in Cloning
• Why Ageing Occurs Are All Under The Guideline Of DNA
• Self Assembling Circuits Using DNA, The Next Computer Breakthrough
• Significance of Discoveries in Genetics and DNA
• Understanding Recombinant DNA Technology
• The Contribution of DNA Profiling to Changing the Crime Solving System
• Understanding How Genetic Engineering Works from the Perspective of the DNA
• The Use of Recombinant DNA Technology
• The Random Amplified Polymorphic DNA Polymerase Chain Reaction
• The Genesis of DNA Profiling and Its Use in the Modern World
• The Effects Of Gene Editing On Human DNA
• Use Of DNA In Criminal Investigations
• Tools and Techniques for DNA Manipulation
• Timeline on Our Understanding of DNA and Heredity
• Rosalind Franklin: Unsung Hero Of The DNA Revolution
• The Impact of the Use of DNA Analysis for Forensic Analysis
• Your DNA: Who Has Access To It And How It Should Be Used
• Structure and Analysis of DNA and Implications for Society
• The Light and Dark Side of DNA Technology
• The Functions Of DNA And Protein Synthesis
• Watson and Crick and the Discovery of DNA’s Structure
• The Uses of DNA Technology in Forensic Science
• The Discovery and Understanding of the Structure of DNA by James Watson and Francis Crick
• The Work of James Watson and Francis Crick on the Exploration of DNA Structure
• Uses Of DNA And Fingerprints In Crime Scene Investigation
• The Structure of DNA and the Risks Inherent in Understanding It
• The Concept and Role of DNA Fingerprinting in Solving Crimes
• How Is DNA Deciphered?
• Which Scientists Participated in the Discovery of DNA?
• What Experiments Did Scientists Use to Discover DNA?
• What Is the Structure of DNA?
• What Are the Methods of Diagnosing Plant Diseases Based on DNA?
• DNA: What Are the Potential Effects on Skeletal Muscle Aging in Humans?
• How Many Crimes Are Solved by DNA?
• What Does Vitamin Help With DNA Repair?
• Why Do Researchers Study DNA?
• Is It Possible to Control the Aids Virus With a DNA Vaccine?
• How Does DNA Help Fight Crime?
• What Are the Analytical Methods of DNA Extraction?
• What Is a DNA Sequence?
• How Would You Analyze the DNA Matches of Identical Twins?
• When Was DNA Discovered?
• How Different Is Human DNA From Animal DNA?
• Is It Possible to Clone the DNA of Animals and Plants?
• How Many DNA Molecules Are in a Chromosome?
• Is It Possible to Artificially Create DNA?
• Can Cancer Be Detected in DNA?
• How Accurate Is DNA Evidence?
• What Is the DNA Replication Process?
• Can Siblings Have Different DNA?
• Why Does ATM Deficiency Accelerate DNA Damage in HIV-Infected Individuals?
• Can DNA Evidence Ever Be Wrong?
• A Bioethical Question: Is DNA Fingerprinting Mandatory?
• Which Part of DNA Carries Genetic Information?
• How Is DNA Used in Research?
• What Are the Types of DNA?
• What Is the Basic Structure of DNA?
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Essays on DNA

The DNA (abbreviation for deoxyribonucleic acid) molecule has a very special place in life science, making a DNA essay a worthy study. Essays on DNA teach us how DNA stores complete information about the structure and properties of the organism. Therefore, knowledge of all the structural features of DNA is fundamentally important. DNA essays often explore the structure of DNA – a famous double helix It was discovered by Watson and Crick in 1953, which started a new era in the history of human civilization – the era of molecular biology and genetics, biotechnology, and molecular medicine. Our DNA essay samples will make you well-equipped for writing your own essay. Simply check out samples of DNA essays below.

The use of biometric identifiers in security systems is an enticing idea and has been embraced by the public following its use in banking systems where the data from iris scanners, facial recognition, and fingerprint scanners is utilized. Biometric identifier locates the user’s details from the central database, whereas the...

Words: 2211

DNA Evidence and its Application in Forensic Investigations DNA evidence is among many scientific tools that have been provided for the investigation of forensic evidence via the analysis of DNA which is a material that makes up one's genetic code. DNA can be retrieved from their hair, blood, skin cells as...

Words: 1083

CRISPR was first discovered by Ishino and coworkers at Osaka University in Japan while cloning a peculiar gene-repeat (Ishino et al. 5429-30). Nearly two decades later, a group of researchers at the food ingredient producer Danisco in Madison, United States, discovered that these CRISPR repetitions in bacteria offered defense against...

From its humble beginnings, forensic science has come a long way. For identification purposes, fingerprints have been used for a very long period. The breadth of forensic discoveries and advancements will be extended by this discipline. The tools used today to identify criminal offenders include DNA testing, impressions, and even...

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Recently, it has been proposed that human DNA and RNA are structurally distinct. As the scientific theory of the origin and evolution of man indicates, the structure, a double helix, of these two salts, i.e., both the RNA and the DNA, has actually been present for billions of years. Numerous...

Words: 1225

Introduction After the use of fingerprints, the use of DNA testing for forensic investigations can be considered the most important invention in the area of criminal investigations. The word "DNA" stands for deoxyribonucleic acid. DNA utilizes biological components like skin, hair, blood, and bodily fluids to identify people. A distinctive genetic...

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The film Gattaca is set in the future, where DNA plays an important part in defining social class and genetic modification of people is common. Vincent, according to Brezina, Enrico, and Amelia, is born and conceived without the assistance of technology (338). Vincent is subjected to strong genetic prejudice and...

The jurors made a critical error in their evaluation of the evidence. With all of the evidence shown to the jurors, it is easy to conclude that there was no tampering with or framing of the evidence in order to frame "the kid" of the crime against his blood father....

The term "signature-tagged mutagenesis" (STM) refers to a technique that allows for the simultaneous screening of numerous different mutants. The method is accomplished by applying a special DNA sequence known as a signature tag to each of the implicated bacteria. Initially, this method was referred to as TN mutagenesis screening...

Words: 4955

An organism classified as a genetically modified organism (GMO) has had its DNA altered or transformed. Recombinant DNA is a process that includes transferring genetic material from one plant or animal to another to create these organisms. The genetic engineering method produced GMOs (Zhang, 2016). The method involves inserting the...

DNA sequence changes can result from cell mutations passed down from a parent organism to its children. Some cell mutations can be advantageous, but the majority are damaging because they result in the cell's ability to perform a specific function being lost. Bacteria naturally experience base pair mutations at a...

Introduction Media, scientists, and governmental agencies have all expressed interest in and opinions about the use of genetic engineering and biotechnology. There are no definitive solutions to the question of what lies ahead for genetically engineered creatures. Organisms that have had their genetic makeup altered by genetic engineering are referred to...

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Locating an Essay’s DNA

I’ve long wondered what it is about abandoned buildings that intrigues me so . Wherever I am, I search them out; were I feeling melodramatic, I might say that they search me out. I always seem to be driving past or near them, in large cities and small towns, though this may have as much to say about a depressed economic climate than about any sixth sense I may claim. At any rate, I find abandoned buildings, and photograph them; the ones I haven’t photographed have imprinted themselves inside me. Were I to explore abandoned buildings in an essay, that essay’s narrow subject would involve the buildings themselves and my narrative relationship to them: where they are; where I am; how I found them; their physical condition and descriptive details, etc.

An essay that deliberates on its narrow subject exclusively can be a pleasing essay, lingering affectionately on sensory description, on evocation of time and place, on regional history, maybe on relevant stories. But that essay’s larger subject is what will draw its readers toward something more valuable and memorable. Here, if I was writing the abandoned-buildings essay, I’d ask the important question, not What? , but Why? And here’s where the essay would turn. Why am I writing about abandoned buildings? I might explore what resonance they have for me on an emotional level, try and chase the sensations that resist language; that’s a tough place to get to, but almost always worthwhile for an essayist. (What I don’t know and what I can’t name.) I might explore less what I see in front of me than why I am here: that is, what brings me? Decrepitude slumming? Ruin romanticizing? Neither of those impulses reflects very well on me, and conflict is usually a good place to linger in an essay. I probably sentimentalize abandoned buildings and their devastating music of loss. Don’t I argue strenuously against sentimentality, resist it? Why do I give in here? What do I gain, or lose? If I sentimentalize ruins, I conveniently ignore, or elide, the genuine suffering such ruins might have brought to the buildings’ owners (whom I might interview) or neighbors (ditto). My essay might open outward to the culture in which the buildings exist in their slow, stubborn demise, the people who once lived inside, or those who live nearby. In moving from the narrow subject (what) to the larger subject (why) the essay gains dimensionality; the heat that’s generated from the friction of the two subjects warms the essay, produces something more mature, round, maybe even valuable.

Here’s the secret: the larger subject is always contained in the DNA of the urge to write; we use the narrow subject to write toward and hopefully discover the larger subject. So, what’s your narrow subject? Where does it take you? Careful: you might not come back.

Joe Bonomo ’s most recent books are  This Must Be Where My Obsession with Infinity Began , a collection of essays, and  Conversations with Greil Marcus . The music columnist at The Normal School literary magazine, he teaches at Northern Illinois University and appears online at  No Such Thing As Was .

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Essay on DNA Replication | Genetics

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In this essay we will discuss about:- 1. Definition of DNA Replication 2. Mechanism of DNA Replication 3. Evidences for Semi-Conservative DNA Replication 4. Models for Replication of Prokaryotic DNA.

Essay # Definition of DNA Replication :

DNA replicates by “unzipping” along the two strands, breaking the hydrogen bonds which link the pairs of nucleotides. Each half then serves as a template for nucleotides available in the cells which are joined together by DNA polymerase. The nucleotides are guanine, cytosine, adenine and thymine. DNA replication or DNA synthesis is the process of copying a double-stranded DNA molecule.

This process is important in all known forms of life and the general mechanisms of DNA replication are the same in prokaryotic and eukaryotic organisms. The process by which a DNA molecule makes its identical copies is referred to as DNA replication. In other words, it is the process of duplicating the DNA to make two identical copies. The main points related to DNA replication are briefly presented below.

1. Time of Replication:

The process of DNA replication takes place during cell division. The DNA replication takes place during S sub stage of interphase. In prokaryotes, DNA replication is initiated before the end of the cell cycle. Eukaryotic cells can only initiate DNA replication at the beginning of S phase.

2. Replication Site:

In humans and other eukaryotes, replication occurs in the cell nucleus, whereas in prokaryotes it occurs in the cytoplasm. Prokaryotes have only one active replication site, but eukaryotes have many.

3. Template Used:

The existing DNA is used as a template for the synthesis of new DNA strands. It is possible that during replication on strand of DNA can replicate continuously and the other discontinuously or in piece. The continuously replicating strand is known as leading strand and the discontinuously replicating strand is known as lagging strand.

When one strand of DNA replicates continuously and other discontinuously, it is called semi-discontinuous replication. Earlier it was thought that DNA replicates discontinuously. But now it is believed that DNA replication is semi-discontinuous.

Short segments of nucleotides are synthesized in the lagging strand of DNA as a result of discontinuous replication. These are called Okazaki after the name of discoverer. Okazaki fragments are about 1,500 bases in length in prokaryotes, and 150 bases in eukaryotes

4. Enzymes Involved:

The process of DNA replication takes place under the control of DNA polymerase. In other words, the process is catalized by the polymerase enzyme. In eukaryotes, four types of polymerase enzymes, viz. alpha, delta, gamma and epsilon are used.

DNA Polymerase alpha and delta replicate the DNA. The alpha is associated with initiation, and delta extends the nascent strands. DNA polymerase epsilon and beta are used for repair. DNA polymerase gamma is used for replication of mitochondrial DNA

In prokaryotes [E. coli], there are three major DNA polymerases: DNA polymerase I, II and III. DNA poly I is found in the highest concentration of all DNA polymerases; it is involved in DNA repair and assists with primary DNA replication. DNA poly II is exclusively involved in repair. DNA poly III is the major DNA polymerase. All DNA polymerases add to the 3′ OH of the existing polynucleotide.

Currently, six families of polymerases (A, B, C. D, X, Y) have been discovered. At least four different types of DNA polymerases are involved in the replication of DNA in animal cells (POLA, POLG, POLD and POLE).

5. Direction of Replication:

The synthesis of one new strand takes place in 5-3 and that of other in opposite (3-5) direction. The replication may take place either in one direction or in both the directions from the point of origin. When replication proceeds in one direction only, it is called unidirectional replication. When the replication proceeds in both the directions, it is called bidirectional replication.

6. Replication Type:

Based on the direction, the replication may be unidirectional or bidirectional. On the basis of continuity, the replication may be continuous or discontinuous.

7. Origin of Replication:

The point of initiation of DNA replication is known as origin. The progress of replication process is measured from the point of origin.

8. Rate of Replication:

In prokaryotic cells the rate of replication is 500 bases per second. In eukaryotic cells the rate of replication- is 50 bases per second. Eukaryotes have 100 to 3,000 times more DNA than prokaryotes.

9. Replication Models:

There are three models which explain the accurate replication of DNA. These are: (i) dispersive replication, (ii) conservative replication, and (iii) semiconservative replication (Fig. 17.1).

These are explained as follows:

(i) Dispersive Replication:

According to this model of replication the two strands of parental DNA break at several points resulting in several pieces of DNA. Each piece replicates and pieces are reunited randomly, resulting in formation of two copies of DNA from single copy. The new DNA molecules are hybrids which have new and DNA in patches (Fig. 17.2). This method of DNA replication is not accepted as it could not be proved experimentally.

(ii) Conservative Replication:

According to this model of DNA replication two DNA molecules are formed from parental DNA. One copy has both parental strands and the other contains both newly synthesized strands (Fig. 17.2). This method is also not accepted as there is no experimental proof in support of this model.

(iii) Semiconservative Replication:

This model of DNA replication was proposed by Watson and Crick. According to this model of DNA replication, both strands of parental DNA separate from each other. Each old strand synthesizes a new strand. Thus each of the two resulting DNA molecules has one parental and one new strand (Fig. 17.3). This model of DNA replication is universally accepted because there are several evidences in support of this mode.

Essay # Mechanism of DNA Replication :

The semi-conservative model (mechanism) of DNA replication consists of six important steps, viz:

(1) Unwinding,

(2) Binding of RNA primase,

(3) Elongation,

(4) Removal of primers,

(5) Termination, and

(6) DNA repair.

These are briefly discussed as follows:

1. Unwinding:

The first major step in the process of DNA, replication is the breaking of hydrogen bonds between bases of the two anti-parallel strands. The unwinding of the two strands is the starting point. The splitting happens in places of the chains which are rich in A-T.

That is because there are only two bonds between Adenine and Thymine, whereas there are three hydrogen bonds between Cytosine and Guanine. The Helicase enzyme splits the two strands. The initiation point where the splitting starts is called “origin of replication”. The structure that is created is known as “Replication Fork”.

2. Binding of RNA Primase:

Synthesis of RNA primer is essential for initiation of DNA replication. RNA primer is synthesized by DNA template near the origin with the help of RNA Primase. RNA Primase can attract RNA nucleotides which bind to the DNA nucleotides of the 3′-5′ strand due to the hydrogen bonds between the bases. RNA nucleotides are the primers (starters) for the binding of DNA nucleotides.

3. Elongation:

The elongation proceeds in both directions, viz. 5′-3′ and 3′-5′ template. The 3′-5′ proceeding daughter strand that uses a 5′-3′ template— is called leading strand because DNA Polymerase ‘a’ can “read” the template and continuously add nucleotides. The 3′-5′ template cannot be “read” by DNA Polymerase a. The replication of this template is complicated and the new strand is called lagging strand.

In the lagging strand the RNA Primase adds more RNA Primers. DNA polymerase a reads the template and lengthens the bubbles. The gap between two RNA primers is called “Okazaki” Fragments. The RNA Primers are necessary for DNA Polymerase a to bind Nucleotides to the 3′ end of them. The daughter strand is elongated with the binding of more DNA nucleotides.

4. Removal of Primers:

The RNA Primers are removed or degraded by DNA polymerase I. This enzyme also catalyzes the synthesis of short DNA segments to replace the primers. The gaps are filled with the action of DNA Polymerase which adds complementary nucleotides to the gaps.

The DNA Ligase enzyme adds phosphate in the remaining gaps of the phosphate-sugar backbone. Each new double helix is consisted of one old and one new chain. This is called semi-conservative replication.

5. Termination:

The termination takes place when the DNA Polymerase reaches to an end of the strands. In other words, it is the separation of replicated linear DNA. After removal of the RNA primer, it is not possible for the DNA Polymerase to seal the gap because there is no primer.

Hence, the end of the parental strand where the last primer binds is not replicated. These ends of linear (chromosomal) DNA consist of noncoding DNA that contains repeat sequences and are called telomeres. A part of the telomere is removed in every cycle of DNA Replication.

6. DNA Repair:

The DNA replication is not completed without DNA repair. The possible errors caused during the DNA replication are repaired by DNA repair mechanism. Enzymes like nucleases remove the wrong nucleotides and the DNA Polymerase fills the gaps. Similar processes also happen during the steps of DNA Replication of prokaryotes though there are some differences.

Essay # Evidences for Semi-Conservative DNA Replication :

Various experiments have demonstrated the semi-conservative mode of DNA replication. Now it is universally accepted that DNA replicates in a semi-conservative manner. There are three important experiments which support that DNA replication is semi-conservative.

These experiments include:

(1) Meselson and Stahl experiment,

(2) Cairns experiment, and

(3) Taylor’s experiment.

1. Meselson and Stahl Experiment [1958] :

Organism Used:

Meselson and Stahl conducted their experiment with common bacteria of human intestine i.e. Escherichia coli.

They used heavy isotope of nitrogen for labelling DNA. The bacteria were grown on culture medium containing heavy isotope of Nitrogen [N15] for 14 generations (30 minutes per generation) to replace the normal nitrogen [N14] of E. coli with heavy nitrogen.

Then the bacteria were transferred to normal nitrogen medium. The density of DNA was determined after one, two and three generations. Principle Involved. It is possible to detect minute differences in density through density gradient centrifugation. District bands are formed in centrifuge tube for different density DNA.

2. Rolling Circle Model of DNA Replication :

This model of circular DNA replication was proposed in 1968. This model explains mechanism of DNA replication in single stranded circular DNA of viruses, e.g. ɸX174, and the transfer of E. coli sex factor (plasmid). The ϕX174 chromosome consists of a single stranded DNA ring (Positive Strand). This model is most widely accepted.

The mechanism of replication consists of following important steps:

(i) Synthesis of New Strand:

First the chromosome becomes double stranded by synthesis of a negative strand. The original strand is positive. The negative strand is synthesized in side of parental positive strand.

(ii) Cut in Outer Strand:

The negative or inner strand remains a close circle and the positive strand is nicked at a specific site by endonuclease enzyme. This enzyme recognizes a particular sequence at this point. Thus a. linear strand with 3′- and 5′-ends is created.

(iii) Formation of Tail:

The original positive strand comes out in the form of a tail of a single linear strand as a consequence of rolling circle. The 5′-end of the broken strand becomes attached to the plasma membrane of the host bacterium.

Such replicating phage DNA is commonly found associated with bacterial membranes. The unbroken parental strand rolls and unwinds as synthesis proceeds, leaving a ‘tail’ which is attached to the membrane.

(iv) Synthesis of New Strand:

The synthesis of new strand takes place along the parental strand at the tail end in a 3-5 direction. The 3′-end serves as a primer for the synthesis of a new DNA strand under the catalytic action of DNA polymerase. The unbroken strand is used as the template for this purpose, and a complementary strand is synthesized. Thus the parental molecule itself is used as a primer for initiating replication.

New DNA is also synthesized in the tail region in discontinuous segments in the 5-3 direction. This synthesis is presumably preceded by the synthesis of an RNA primer under the catalytic action of RNA polymerase. The tail is cut-off by a specific endonuclease into a unit length progeny rod.

(v) Cutting of Tail:

Now the tail is cut-off into a linear segment by endonuclease. The linear segment becomes circular by joining two ends with the help of ligage enzyme. Thus a new circular molecule is formed which can become new rolling circle and replicate further.

Genetic information is preserved in the single stranded template ring which remains circular and serves as an endless template. There is no swiveling problem or creation of torque in the rolling circle model. As the strands unwind the 3′-end is free to rotate on the unbroken strand. The growing point itself thus serves as a swivel.

Evidence for the rolling circle model has been obtained from the replication of several viruses (M13, P2, T4, λ), replication resulting in transfer of genetic material during mating of bacteria, and the special DNA synthesis during oogenesis in Xenopus.

Related Articles:

• 6 Basic Rules for DNA Replication | Genetics
• Replication of DNA: 2 Things to Know About

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A Mammoth First: 52,000-Year-Old DNA, in 3-D

A “fossil chromosome” preserves the structure of a woolly mammoth’s genome — and offers a better grasp of how it once worked.

The foot of a woolly mammoth excavated from the permafrost in Siberia. In a new study, scientists extracted mammoth DNA that retained its original architecture, a feat never before achieved with an ancient genetic sample. Credit... Love Dalén/Stockholm University

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By Siobhan Roberts

• July 11, 2024

In 2018 an international team of scientists — from labs in Houston, Copenhagen, Barcelona and beyond — got their hands on a remarkable biological specimen: a skin sample from a 52,000-year-old woolly mammoth that had been recovered from the permafrost in Siberia. They probed the sample with an innovative experimental technique that revealed the three-dimensional architecture of the mammoth’s genome. The resulting paper was published on Thursday in the journal Cell.

Hendrik Poinar, an evolutionary geneticist at McMaster University in Canada, was “floored” — the technique had successfully captured the original geometry of long stretches of DNA, a feat never before accomplished with an ancient DNA sample. “It’s absolutely beautiful,” said Dr. Poinar, who reviewed the paper for the journal.

The typical method for extracting ancient DNA from fossils, Dr. Poinar said, is still “kind of cave man.” It produces short fragments of code composed of a four-letter molecular alphabet: A (adenine), G (guanine), C (cytosine), T (thymine). An organism’s full genome resides in cell nuclei, in long, unfragmented DNA strands called chromosomes. And, vitally, the genome is three-dimensional; as it dynamically folds with fractal complexity, its looping points of contact help dictate gene activity.

“To have the actual architectural structure of the genome, which suggests gene expression patterns, that’s a whole other level,” Dr. Poinar said.

“It’s a new kind of fossil, a fossil chromosome,” said Erez Lieberman Aiden , a team member who is an applied mathematician, a biophysicist and a geneticist and directs the Center for Genome Architecture at Baylor College of Medicine in Houston. Technically, he noted, it is a non-mineralized fossil, or subfossil, since it has not turned to stone.

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World-first study decodes the DNA structure of a 52, 000-year -old woolly mammoth sample

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In a world-first study, we have revealed and analysed remarkably preserved fragments of ancient DNA from the skin of a woolly mammoth.

For the first time, we’ve been able to understand how the genetic instructions for this extinct species were organised inside its cells. This is known as genome architecture – the three-dimensional arrangement of DNA in the cell’s nucleus.

The research, published today in Cell , was a mammoth international effort, including teams from the United States, Australia, Denmark, Spain, Sweden, Russia and Norway. The discovery greatly enhances our understanding of a lost species.

By examining the genome architecture of the woolly mammoth, we can uncover the secrets of its survival in harsh environments – and its eventual extinction around 10,000 years ago . Our discovery also brings unprecedented insights into ancient DNA and opens up new avenues for research in this field.

A new look at an extinct species

Genome architecture influences how genes are turned on or off. This impacts everything from development to disease. In modern species, scientists study genome architecture to understand how the genes are regulated, and how the cells of the organism function.

When applied to ancient DNA, it can illuminate the biological and environmental history of an extinct species – such as the woolly mammoth.

Along with some proteins, the DNA within cells is stashed in what’s known as chromatin . It packages the long DNA molecules into a more compact, dense shape. This allows them to fit inside the cell nucleus.

The chromatin we found in our woolly mammoth sample from Siberia was remarkably well preserved, despite the animal having died 52,000 years ago.

The mammoth would have rapidly frozen after death. Its tissue was transformed due to the cold, dry and stable conditions. Although typically DNA degrades over time, in our sample we found it preserved in a glass-like state.

At the nanoscale, it’s akin to a bumper-to-bumper traffic jam where individual particles – in this case ancient DNA fragments – are immobilised and unable to move far from each other, even over thousands of years.

Usually, the study of ancient genome architecture is particularly challenging because DNA falls apart relatively quickly. However, we adapted a genomic analysis technique that maps chromatin interactions, allowing us to delve into the ancient DNA structures we found in the sample.

We could count the individual chromosomes and learn that mammoths had 28 – just like their closest living relatives, elephants. Then, we dug deeper.

A strikingly familiar pattern

When we compared the genome architecture of the mammoth and the Asian elephant living today, we found a striking similarity. This suggests the ancient DNA sample still shows useful biological information.

The sample was so detailed, not only could we see which genes were activated in the mammoth genome, but also why. One key discovery was what we call “mammoth altered regions”. These were changes in gene activity specific to the species.

For instance, we found that genes involved in hair development and immune response showed different activity patterns in mammoths compared to elephants.

The woolly mammoth had several unique physical traits adapted for cold environments. These included a thick, shaggy coat of fur and large tusks curving upwards.

They also had relatively small ears to minimise heat loss, and a specialised fat layer under the skin for insulation. These adaptations helped them thrive in ice age conditions.

A groundbreaking step forward

Our detailed work on the woolly mammoth’s genome architecture has provided a window into the past. By comparing them to their living relatives, we’ve found that crucial chromatin structures and gene regulation mechanisms have been preserved for more than 50,000 years.

This shows just how resilient genomic architecture can be on a grand evolutionary scale. The methods we developed to peer at the chromatin structures now open up new avenues of research.

As we continue to explore these ancient blueprints, we may uncover further secrets of how this extinct species adapted and thrived in its environment.

Our discovery may spark thoughts of resurrecting the woolly mammoth. However, our insights from studying ancient DNA might actually help the conservation of existing species.

What happened to the woolly mammoth in the Siberian permafrost was essentially natural biobanking – preservation and storage of genetic material. If we do this proactively for currently endangered species, we can safeguard their genetic diversity for future generations.

This would also provide a crucial resource for scientific research and conservation efforts. Just as the frozen mammoths have yielded knowledge about their adaptations and evolutionary pathways, modern biobanking efforts can offer insights into species’ resilience to environmental changes, disease resistance, and other critical traits.

This knowledge is vital for informing conservation strategies. It will help us ensure the long-term survival of biodiversity in a rapidly changing world.

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‘A history of contact’: Princeton geneticists are rewriting the narrative of Neanderthals and other ancient humans

Illustration by Matilda Luk, Office of Communications

Ever since the first Neanderthal bones were discovered, people have wondered about these ancient hominins. How are they different from us? How much are they like us? Did our ancestors get along with them? Fight them? Love them? The recent discovery of a group called Denisovans, a Neanderthal-like group who populated Asia and Oceania, added its own set of questions.

Now, an international team of geneticists and AI experts are adding whole new chapters to our shared hominin history. Under the leadership of Joshua Akey, a professor in Princeton’s Lewis-Sigler Institute for Integrative Genomics, the researchers have found a history of genetic intermingling and exchange that suggests a much more intimate connection between these early human groups than previously believed.

“This is the first time that geneticists have identified multiple waves of modern human-Neanderthal admixture,” said Liming Li, a professor in the Department of Medical Genetics and Developmental Biology at Southeast University in Nanjing, China, who performed this work as an associate research scholar in Akey’s lab.

“We now know that for the vast majority of human history, we've had a history of contact between modern humans and Neanderthals,” said Akey. The hominins who are our most direct ancestors split from the Neanderthal family tree about 600,000 years ago, then evolved our modern physical characteristics about 250,000 years ago.

“From then until the Neanderthals disappeared — that is, for about 200,000 years — modern humans have been interacting with Neanderthal populations,” he said.

The results of their work appear in the current issue of the journal Science.

Neanderthals, once stereotyped as slow-moving and dim-witted, are now seen as skilled hunters and tool makers who treated each other’s injuries with sophisticated techniques and were well adapted to thrive in the cold European weather.

(Note: All of these hominin groups are humans, but to avoid saying “Neanderthal humans,” “Denisovan humans,” and “ancient-versions-of-our-own-kind-of-humans,” most archaeologists and anthropologists use the shorthand Neanderthals, Denisovans, and modern humans.)

Mapping the gene flow

Using genomes from 2,000 living humans as well as three Neanderthals and one Denisovan, Akey and his team mapped the gene flow between the hominin groups over the past quarter-million years.

The researchers used a genetic tool they designed a few years ago called IBDmix, which uses machine learning techniques to decode the genome. Previous researchers depended on comparing human genomes against a “reference population” of modern humans believed to have little or no Neanderthal or Denisovan DNA.

Akey’s team has established that even those referenced groups, who live thousands of miles south of the Neanderthal caves, have trace amounts of Neanderthal DNA, probably carried south by voyagers (or their descendants).

With IBDmix, Akey’s team identified a first wave of contact about 200-250,000 years ago, another wave 100-120,000 years ago, and the largest one about 50-60,000 years ago.

That contrasts sharply with previous genetic data. “To date, most genetic data suggests that modern humans evolved in Africa 250,000 years ago, stayed put for the next 200,000 years, and then decided to disperse out of Africa 50,000 years ago and go on to people the rest of the world,” said Akey.

“Our models show that there wasn’t a long period of stasis, but that shortly after modern humans arose, we've been migrating out of Africa and coming back to Africa, too,” he said. “To me, this story is about dispersal, that modern humans have been moving around and encountering Neanderthals and Denisovans  much more than we previously recognized.”

That vision of humanity on the move coincides with the archaeological and paleoanthropological research suggesting cultural and tool exchange between the hominin groups.

A DNA insight

Li and Akey’s key insight was to look for modern-human DNA in the genomes of the Neanderthals, instead of the other way around. “The vast majority of genetic work over the last decade has really focused on how mating with Neanderthals impacted modern human phenotypes and our evolutionary history — but these questions are relevant and interesting in the reverse case, too,” said Akey.

They realized that the offspring of those first waves of Neanderthal-modern matings must have stayed with the Neanderthals, therefore leaving no record in living humans. “Because we can now incorporate the Neanderthal component into our genetic studies, we are seeing these earlier dispersals in ways that we weren't able to before,” Akey said.

The final piece of the puzzle was discovering that the Neanderthal population was even smaller than previously believed.

Genetic modeling has traditionally used variation — diversity — as a proxy for population size. The more diverse the genes, the larger the population. But using IBDmix, Akey’s team showed that a significant amount of that apparent diversity came from DNA sequences that had been lifted from modern humans, with their much larger population.

As a result, the effective population of Neanderthals was revised down from about 3,400 breeding individuals down to about 2,400.

How Neanderthals vanished

Put together, the new findings paint a picture of how the Neanderthals vanished from the record, some 30,000 years ago.

“I don’t like to say ‘extinction,’ because I think Neanderthals were largely absorbed,” said Akey. His idea is that Neanderthal populations slowly shrank until the last survivors were folded into modern human communities.

This “assimilation model” was first articulated by Fred Smith, an anthropology professor at Illinois State University, in 1989. “Our results provide strong genetic data consistent with Fred’s hypothesis, and I think that's really interesting,” said Akey.

“Neanderthals were teetering on the edge of extinction, probably for a very long time,” he said. “If you reduce their numbers by 10 or 20%, which our estimates do, that's a substantial reduction to an already at-risk population.

“Modern humans were essentially like waves crashing on a beach, slowly but steadily eroding the beach away. Eventually we just demographically overwhelmed Neanderthals and incorporated them into modern human populations.”

“ Recurrent gene flow between Neanderthals and modern humans over the past 200,000 years ,” by Liming Li, Troy J. Comi , Rob F. Bierma, and Joshua M. Akey, appears in the July 13 issue of the journal Science (DOI: 10.1126/science.adi1768 ). This research was supported by the National Institutes of Health (grant R01GM110068 to JMA).

Related Stories

Origin story: Rewriting human history through our DNA .

Joshua Akey, a professor in the Lewis-Sigler Institute for Integrative Genomics, uses "genetic archaeology" to reveal a larger picture of how we evolved as a species. The research divulges a complex history of the intermixing of early humans, indicative of several millennia of population movements across the globe.

New study identifies Neanderthal ancestry in African populations and describes its origin .

After sequencing the Neanderthal genome, scientists discovered all modern humans carry some Neanderthal ancestry in their DNA — including Africans, which was previously not known. 

Modern Flores Island pygmies show no genetic link to extinct 'hobbits' .

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Genomic detectives crack the case of the missing heritability .

Despite years of research, the genetic factors behind many human diseases and characteristics remain unknown, and has been called the "missing heritability" problem. A new study by Princeton University researchers, however, suggests that heritability in humans may be hidden due only to the limitations of modern research tools, but could be discovered if scientists know where (and how) to look.  

'Fantastic giant tortoise,' believed extinct, confirmed alive in the Galápagos .

A tortoise from a Galápagos species long believed extinct has been found alive and now confirmed to be a member of the species. Fernanda, named after her Fernandina Island home, is the first of her species identified in more than a century.

A gene that shaped the evolution of Darwin's finches .

Researchers from Princeton University and Uppsala University in Sweden have identified a gene in the Galápagos finches studied by English naturalist Charles Darwin that influences beak shape and that played a role in the birds' evolution from a common ancestor more than 1 million years ago. The study illustrates the genetic foundation of evolution, including how genes can flow from one species to another, and how different versions of a gene within a species can contribute to the formation of entirely new species.

In one of nature's innovations, a single cell smashes and rebuilds its own genome .

A study led by Princeton University researchers found that a pond-dwelling, single-celled organism has the remarkable ability to break its own DNA into nearly a quarter-million pieces and rapidly reassemble those pieces when it's time to mate. This elaborate process could provide a template for understanding how chromosomes in more complex animals such as humans break apart and reassemble, as can happen during the onset of cancer.

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The dubious consent question at the heart of the Human Genome Project

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Launched in 1990, a major goal of the Human Genome Project was to sequence the human genome as fully as possible. In 2003, project scientists unveiled a genome sequence that accounted for over 90% of the human genome — as complete as possible for the technology of the time. Darryl Leja, NHGRI/Flickr hide caption

Launched in 1990, a major goal of the Human Genome Project was to sequence the human genome as fully as possible. In 2003, project scientists unveiled a genome sequence that accounted for over 90% of the human genome — as complete as possible for the technology of the time.

The Human Genome Project was a massive undertaking that took more than a decade and billions of dollars to complete. For it, scientists collected DNA samples from anonymous volunteers who were told the final project would be a mosaic of DNA. Instead, over two-thirds of the DNA comes from one person: RP11. No one ever told him. Science journalist Ashley Smart talks to host Emily Kwong about his recent investigation into the decision to make RP11 the major donor — and why unearthing this history matters to genetics today.

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I have the honor to enclose a report of the names and Salaries of the persons employed in the Department of State, in pursuance of an Act, "Intituled’ an Act to regulate and fix the Compensation of Clerks, &c.". I have the honor to be, very respectfully, Your obt. Servt.

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In pursuance of the Act of Congress entitled, "An Act to regulate and fix the compensation of Clerks, &c. the Secretary of State has the honor to submit to Congress, the annexed, list of persons employed in his office, during the year 1807, and to report that the business of the Department generally is in a state of progressive increase; hence it has been found impracticable to bestow that prompt and regular attention to titles, and to the issuing patents for lands which is desirable, especially at a period of peculiar increase in the business growing out of our foreign relations. Some contemplated changes too in the mode of conducting the business of the Office will, for a time, increase the labour of it. It is his opinion, therefore, that the public service would be promoted, as stated in the report made to the last Congress, by a provision, at least sufficient for the employment of another Clerk. All which is respectfully submitted.

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The evolution and mutation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgent concerns as they pose the risk of vaccine failure and increased viral transmission. However, affordable and scalable tools allowing rapid identification of SARS-CoV-2 variants are not readily available, which impedes diagnosis and epidemiological surveillance. Here we present a colorimetric nucleic acid assay named MARVE (multiplexed, preamplification-free, single-nucleotide-resolved viral evolution) that is convenient to perform and yields single-nucleotide resolution. The assay integrates nucleic acid strand displacement reactions with enzymatic amplification to colorimetrically sense viral RNA using a metal ion-incorporated DNA probe (TEprobe). We provide detailed guidelines to design TEprobes for discriminating single-nucleotide variations in viral RNAs, and to fabricate a test paper for the detection of SARS-CoV-2 variants of concern. Compared with other nucleic acid assays, our assay is preamplification-free, single-nucleotide-resolvable and results are visible via a color change. Besides, it is smartphone readable, multiplexed, quick and cheap ($0.30 per test). The protocol takes ~2 h to complete, from the design and preparation of the DNA probes and test papers (~1 h) to the detection of SARS-CoV-2 or its variants (30–45 min). The design of the TEprobes requires basic knowledge of molecular biology and familiarity with NUPACK or the Python programming language. The fabrication of the origami papers requires access to a wax printer using the CAD and PDF files provided or requires users to be familiar with AutoCAD to design new origami papers. The protocol is also applicable for designing assays to detect other pathogens and their variants.

MARVE is a paper-based, preamplification-free assay for the detection of viral variants using toehold exchange (TE) DNA probes. The TEprobe binds to the target viral RNA and starts an enzymatic reaction, which results in low-pH conditions and a color change visible to the eye.

The high specificity of a nucleic acid test, combined with low cost and ease of use, makes MARVE suitable for home testing.

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A paper-based assay for the colorimetric detection of SARS-CoV-2 variants at single-nucleotide resolution

Simultaneous identification of viruses and viral variants with programmable DNA nanobait

Multiplexed discrimination of SARS-CoV-2 variants via plasmonic-enhanced fluorescence in a portable and automated device

Data availability.

The data supporting the findings of this study are available within the source data and the supporting primary research papers 16 , 17 . Source data are provided with this paper.

Code availability

The mobile web apps for COVID-19 self-testing and viral contamination monitoring in food can be visited at http://47.109.38.99/origami1/ or at http://47.109.38.99/origami2/ , respectively. The code for designing TEprobes is available on GitHub at https://github.com/Nelson233/TEprobe-design . The code for the two web apps is provided on GitHub at https://github.com/Nelson233/origami1 and https://github.com/Nelson233/origami2 , respectively. The code for image analysis using MATLAB software is available on GitHub at https://github.com/Nelson233/MARVEL .

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Acknowledgements

We thank all authors of the primary research paper. The work was funded by the National Key Research and Development Program of China (2023YFB3208302 and 2021YFA1200104), the New Cornerstone Investigator Program, National Natural Science Foundation of China (22074100 and 22027807), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB36000000) and Tsinghua-Vanke Special Fund for Public Health and Health Discipline Development (2022Z82WKJ003).

Author information

These authors contributed equally: Ting Zhang, Yuxi Wang.

Authors and Affiliations

Department of Chemistry, Center for BioAnalytical Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, New Cornerstone Science Institute, Tsinghua University, Beijing, China

Ting Zhang, Xucong Teng & Jinghong Li

College of Biomass Science and Engineering, Department of Respiration and Critical Care Medine, West China Hospital, Sichuan University, Chengdu, China

Ting Zhang, Yuxi Wang & Ruijie Deng

Beijing Institute of Life Science and Technology, Beijing, China

Xucong Teng & Jinghong Li

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Contributions

J.L. and R.D. conceived and designed the protocol. R.D. and T.Z. developed the protocol. T.Z., R.D., Y.W. and X.T. performed the experiments and analyzed the data. R.D. and T.Z. wrote the manuscript. J.L. edited the manuscript. All authors read, commented on and accepted the final manuscript.

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Correspondence to Ruijie Deng or Jinghong Li .

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Key references that have used this protocol

Zhang, T. et al. Nat. Biomed. Eng . 6 , 957–967 (2022): https://doi.org/10.1038/s41551-022-00907-0

Zhang, T. et al. Nat. Commun . 14 , 4327 (2023): https://doi.org/10.1038/s41467-023-39952-x

Supplementary information

Supplementary information.

Supplementary Figs. 1–7 and Tables 1 and 2.

Supplementary Video 1

The illustration of paper folding using the enclosure.

Supplementary Data 1

The original CAD file of eight-site origami paper.

Supplementary Data 2

The PDF file of eight-site origami paper.

Supplementary Data 3

The original CAD file of four-site origami paper

Supplementary Data 4

The PDF file of four-site origami paper.

Supplementary Data 5

The original file of the enclosure.

Supplementary Data 6

The original CAD file of 100-site origami paper.

Supplementary Data 7

The PDF file of 100-site origami paper.

Source data

Source data fig. 10.

Statistical source data.

Source Data Fig. 11

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Zhang, T., Wang, Y., Teng, X. et al. Preamplification-free viral RNA diagnostics with single-nucleotide resolution using MARVE, an origami paper-based colorimetric nucleic acid test. Nat Protoc (2024). https://doi.org/10.1038/s41596-024-01022-x

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Received : 27 October 2023

Accepted : 08 May 2024

Published : 18 July 2024

DOI : https://doi.org/10.1038/s41596-024-01022-x

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