INTRODUCTION TO GENES

DNA code is a sequence of chemicals that form information that control how humans are made and how they work. It is a digital code but it is not binary, but quaternary with 4 distinct items. The encoding information in an ordered sequence of 4 different symbols called "bases", typically denoted A, C, G, and T.

• A: adenosine
• C: cytosine
• G: guanine
• T: thymine

These 4 substances are the fundamental "bits" of information in the genetic code, and are called "base pairs" because there is actually 2 substances per "bit", as discussed later. Everything else is built on top of this basis of 4 DNA digits.
The entirety of human DNA code, called the "human genome", is about 3 million bases in total. Every human being has 2 copies of this code, one copy from each parent, so a human's cell DNA contains a total of around 6 billion bases. In computer terms, this is around 6 Gigabytes of symbols, or more like 1 Gigabyte if compacted, since it's about 2 binary bits of information per A/C/G/T base pair. DNA molecules are linear in a twisted double-helix, with a start and an end, and do not contain any cycles.
Chromasomes: These 6 billion odd base pairs are split amongst 46 chromasomes. Each person gets 2 pairs of chromasomes, 23 from each parent, to total 46 chromasomes per human cell. A chromasome is the largest form of a DNA molecule, with a large sequence of DNA codes, of differing lengths, usually hundreds of millions of base pairs in each chromasome. Chromasomes are independent molecules of DNA, with the typical double-helix, a start and end, but no cycles. Chromasomes are physically large enough to be seen on high power microscopes.
Genes: Each chromasome has subsequences of DNA bases that encode particular features, and these are called "genes". Thus genes are not independent molecules, but are abstract sequences within chromasomes. All genes have different lengths. Genes are too small to be physically seen on a microscope, but are analyzed using indirect chemical, molecular, and computational methods. The total number of distinct genes in the human genome is believed to be around 30,000 genes according to the Human Genome Project.
So the hierarchy of terminology for genetic components is something like:

• Base pair: the smallest element, a single DNA base-4 compound A, C, G, or T.
• Gene: a medium-size sequence of around 100,000 DNA base pairs, like a sub-module
• Chromasome: a large sequence of hundreds of millions of DNA base pairs, like a computer program file
• Human genome: the entirety of human DNA program code: 2 pairs of 23 distinct chromasomes, adding to around 6 billion DNA base pairs

Every individual has a unique genetic program, though all human DNA shares much common code too. A lot of genes and other DNA subsequences are modified or move around within the DNA of a species, such as when they are inherited from parents at conception. DNA does not usually change within a particular individual's body, though this can occur rarely from cell mutations (e.g. some cancer cells) and also genetic damage such as from radiation or toxic chemical exposure.

CHROMOSOMES

CHROMOSOMES

Each person has 46 chromasomes, in pairs of 2, with 23 from each parent. So there are really 23 distinct chromasomes, and each body cell effectively has 2 different copies of the DNA code, half from each parent.
Each chromasome is distinct and whole. They are ordered, and have clear start and end sequences. In a sense, they are like a file of computer code.
The 23 distinct chromasomes are known and named and have a common structure for each human. The first 22 chromasomes are just named in numbers, simply chromasome 1 through chromasome 22. The name for one of these 22 chromasomes is an "autosome".
The 23rd chromasome is the sex chromasome, which is called either "X" or "Y". Every person has a pair of sex chromasomes, one from each parent. However, unlike the other 22 pairs of chromasomes, a human does not necessarily have 2 similar chromasomes. A male person has a pair of different chromasomes, an X and a Y chromasome, and is usually written as XY. A female has two X chromasomes and is called XX.
The key issue about chromasomes is to understand their role in reproduction. Firstly, let's make some observations about reproduction:

• Children are similar to both parents, with similar traits, but are not identical to either parent.
• Siblings look different, despite sharing the same parents.
• Male and female children occur in about a 50-50 split.

To understand these features, we have to understand how chromasomes are distributed during reproduction. Every person has 46 chromasomes, 23 from the father, 23 from the mother. But the father has 46 chromasomes and so does the mother. Each sperm cell in the father gets 23 chromasomes, and similarly an egg cell gets 23 chromasomes from the mother's set of 46. For each autosome 1..22, the gamete (sperm or egg) gets one of the chromasomes, randomly, without regard to which grandparent the chromasome originally came from. For the sex chromasomes, the egg cell gets one of the mother's X chromasomes, and the sperm gets either the X or Y from the father's chromasomes. Hence, the number of permutations of chromasomes in a father's sperm cell is 2^23, and similarly the number of egg chromasome permuations is also 2^23. So even with the same parents, and even with only entire chromasomes inherited, the number of siblings that can be created is about 2^46.
However, chromosomes are changed during reproduction. They are a natural part of the process. Small or large chunks of chromosome material are swapped during reproductive cell creation. This is called crossover. Thus, the total number of possibilities is even huger than the number purely from simple swapping over.

Non-Gene DNA Sequences

Genes are the best understood subsequence of DNA code. Most genes clearly encode the data sequence representing a particular protein. However, all of the genes together are only a small part of DNA code. The 30,000 odd genes in human DNA might only make up 4% of human DNA.
So what is the other DNA code for? These DNA sequences are the least understood of all genetic issues. The main theory is that these DNA sequences are the control mechanisms, that control when particular genes are activated. If the genes are the data sequences for proteins, the remainder must be the real code. This code presumably controls when the genes are activated, so that human growth follows its normal timetables. It probably also controls how much a gene is activated, controlling how much of each protein is produced by a gene.

DNA and RNA

There are actually 2 main types of nucleic substances within cell nuclei that process information. DNA is the basic form within chromasomes, that is hard-coded into every cell. RNA is a more temporary form that is used to process subsequences of DNA messages. RNA is an intermediate form used to execute the portions of DNA that a cell is using. For example, in the synthesis of proteins, DNA is copied to RNA, which is then used to create proteins: DNA->RNA->Proteins.
The structure of DNA and RNA are very similar. They are both ordered sequences of 4 types of substances: ACGT for DNA, and ACGU for RNA. Thus RNA uses the same three ACG substances, but uses U (uracil) instead of T (thymine). The molecules uracil and thymine are only slightly different chemically. In DNA, there is pairing between AT and CG, and in RNA, the pairings are AU and CG, but since RNA is not double-stranded, this pairing is much rarer. Hence, RNA has the 4 substances:

• A: adenosine
• C: cytosine
• G: guanine
• U: uracil

Typically, DNA is created from RNA, and this is done by faithfully copying the sequence of base pairs, with the only change converting T to U. Hence, an RNA copy of a DNA sequence encodes the identical information, though it uses a slightly different set of 4 substances.
The differences between DNA and RNA are also many. The underlying sugar molecule that traps the 4 bases is different: deoxyribose in DNA, ribose in RNA. DNA is two strands wrapped in a double-helix, but RNA is a single strand.

Genes: Protein Data Sequences in the DNA Code

Some parts of DNA sequences are known to be purely data. These are the "genes". The best understood aspect of DNA coding is the encoding of amino acid information in genes that is used by the body to synthesize proteins. These are data blocks that represent protein structures.
All proteins are substances made up of only 20 basic building blocks called amino acids. Proteins are ordered sequences of these 20 amino acids. Another terminology is that an amino acid is a "peptide" and a protein is a sequence of many peptides called a "polypeptide".
So how does DNA encode the structure of a protein? It uses triplets of base pairs. There are 4x4x4=64 possible combinations in a base pair triplet, and only 20 amino acids. Some extra codes are used as start and stop signal markers at each end of the data sequence. Other triplets are mapped so that more than one triplet can represent a particular amino acid. However, the representation is unique across all DNA mapping base pair triplets to the 20 amino acids:

• 1. Phenylalanine (Phe): UUU, UUC
• 2. Leucine (Leu): UUA, UUG
• 3. Isoleucine (Ile): AUU, AUC, AUA
• 4. Methionine (Met): AUG
• 5. Valine (Val): GUU, GUC, GUA, GUG
• 6. Serine (Ser): UCU, UCC, UCA, UCG, AGU, ACG
• 7. Proline (Pro): CCU, CCC, CCA, CCG
• 8. Threonine (Thr): ACU, ACC, ACA, ACG
• 9. Alanine (Ala): GCU, GCC, GCA, GCG
• 10. Tyrosine (Tyr): UAU, UAC
• 11. Histidine (His): CAU, CAC
• 12. Glutamine (Gln): CAA, CAG
• 13. Asparagine (Asn): AAU, AAC
• 14. Lysine (Lys): AAA, AAG
• 15. Aspartic acid (Asp): GAU, GAC
• 16. Glutamic acid (Glu): GAA, GAG
• 17. Cysteine (Cys): UGU, UGC
• 18. Tryptophan (Trp): UGG
• 19. Arginine (Arg): CGU, CGC, CGA, CGG, AGA, AGG
• 20. Glycine (Gly): GGU, GGC, GGA, GGG

In addition, the following triplet codes are special:

• STOP: UAA, UAG, UGA
• START: AUG (same code as the Methionine amino acid)

Clearly, there are not unique 1-1 mappings of triplets to amino acids. However, although there is redundancy, it is not ambiguous. Any triplet can represent only 1 amino acid.
Why this redundancy? Perhaps there is some meaning to it? Perhaps simply a primitive form of error prevention? Perhaps it is simply an accident of nature that occurs because 3 digits were needed, since 2 DNA digits could only encode 4x4=16 codes, which is not enough to represent the 20 amino acids and start/stop codes.
This DNA encoding appears to be almost the same for all genetics on the planet. A few species of single-celled protists have slightly different codes.

The DNA data sequences are of varying length depending on the size of the protein. Proteins can range from tiny proteins with about 50 amino acids to huge proteins with 5,000 amino acids.
The DNA start and stop sequences are not the same as the RNA start and stop triplets. DNA has a promoter sequence to show where RNA should start to be copied, and a terminator sequence to tell RNA where to stop. The RNA then uses only a single triplet as the start and stop markers. The DNA promoter and terminator sequences are more complex.
Introns: Surprisingly, not all of the DNA code is useful. Certain sequences called "introns" are simply occurred. These are like comments in protein coding sequences. They are transcribed to mRNA properly, but then they are excised from the mRNA to produce the final mRNA. The resulting mRNA is the same order and codes as the original mRNA, but with the introns sequences removed.

RNA Data Sequences in DNA

Proteins are not the only substances that are synthesized directly from data within the DNA. Some forms of RNA are specialized, and also have their formula encoded directly in digital DNA formulae.
Not all types of RNA are temporary intermediate forms with their form depending on whatever DNA they are copying. There are certain forms of RNA that have a particular form that is the same across all individuals. Some of these special-purpose RNA forms are:

• tRNA: transfer RNA
• rRNA: ribosome RNA

There are exactly 20 forms of tRNA, one each to transfer a particular amino acid. tRNA molecules contain about 75-80 bases. tRNA recognizes one of the 64 triplets, and matches it to one of the 20 amino acids. Since there are 20 tRNA types, and not 64, each tRNA molecule has to recognize more than one triplet ordering as a match.
The DNA code contains multiple repetitions of the codes for tRNA and rRNA. About 280 copies are spread over 5 chromosomes. Presumably, this allows each cell to make multiple copies of tRNA and rRNA molecules at once from its single copy of the DNA.

Executing the DNA Program: Parallel Execution

Every cell has a full copy of the entire DNA, complete with around 6 billion DNA base pairs jammed into the cell's nucleus. Whenever cells divide to replicate, they duplicate the entire DNA code so that each cell retains a full DNA copy.
The only cells that do not have the entire DNA code are reproductive sperm or egg cells that have only 23 chromasomes each, and thus only about a half copy of DNA.

VIDEO OF DNA PRINTING

DNA Fingerprinting in Human Health and Society

Like the fingerprints that came into use by detectives and police labs during the 1930s, each person has a unique DNA fingerprint. Unlike a conventional fingerprint that occurs only on the fingertips and can be altered by surgery, a DNA fingerprint is the same for every cell, tissue, and organ of a person. It cannot be altered by any known treatment. Consequently, DNA fingerprinting is rapidly becoming the primary method for identifying and distinguishing among individual human beings. An additional application of DNA fingerprint technology is the diagnosis of inherited disorders in adults, children, and unborn babies. The technology is so powerful that, for example, even the blood-stained clothing of Abraham Lincoln could be analyzed for evidence of a genetic disorder called Marfan's Syndrome. The Structure of DNA The characteristics of all living organisms, including humans, are essentially determined by information contained within DNA that they inherit from their parents. The molecular structure of DNA can be imagined as a zipper with each tooth represented by one of four letters (A, C, G, or T), and with opposite teeth forming one of two pairs, either A-T or G-C. The letters A, C, G, and T stand for adenine, cytosine, guanine, and thymine, the basic building blocks of DNA. The information contained in DNA is determined primarily by the sequence of letters along the zipper. For example, the sequence ACGCT represents different information than the sequence AGTCC in the same way that the word "POST" has a different meaning from "STOP" or "POTS," even though they use the same letters. The traits of a human being are the result of information contained in the DNA code. Living organisms that look different or have different characteristics also have different DNA sequences. The more varied the organisms, the more varied the DNA sequences. DNA fingerprinting is a very quick way to compare the DNA sequences of any two living organisms. Making DNA Fingerprints DNA fingerprinting is a laboratory procedure that requires six steps: 1: Isolation of DNA. DNA must be recovered from the cells or tissues of the body. Only a small amount of tissue - like blood, hair, or skin - is needed. For example, the amount of DNA found at the root of one hair is usually sufficient. 2: Cutting, sizing, and sorting. Special enzymes called restriction enzymes are used to cut the DNA at specific places. For example, an enzyme called EcoR1, found in bacteria, will cut DNA only when the sequence GAATTC occurs. The DNA pieces are sorted according to size by a sieving technique called electrophoresis. The DNA pieces are passed through a gel made from seaweed agarose (a jelly-like product made from seaweed). This technique is the biotechnology equivalent of screening sand through progressively finer mesh screens to determine particle sizes. 3: Transfer of DNA to nylon. The distribution of DNA pieces is transferred to a nylon sheet by placing the sheet on the gel and soaking them overnight. 4-5: Probing. Adding radioactive or colored probes to the nylon sheet produces a pattern called the DNA fingerprint. Each probe typically sticks in only one or two specific places on the nylon sheet. 6: DNA fingerprint. The final DNA fingerprint is built by using several probes (5-10 or more) simultaneously. It resembles the bar codes used by grocery store scanners. Uses of DNA Fingerprints DNA fingerprints are useful in several applications of human health care research, as well as in the justice system. Diagnosis of Inherited Disorders DNA fingerprinting is used to diagnose inherited disorders in both prenatal and newborn babies in hospitals around the world. These disorders may include cystic fibrosis, hemophilia, Huntington's disease, familial Alzheimer's, sickle cell anemia, thalassemia, and many others. Early detection of such disorders enables the medical staff to prepare themselves and the parents for proper treatment of the child. In some programs, genetic counselors use DNA fingerprint information to help prospective parents understand the risk of having an affected child. In other programs, prospective parents use DNA fingerprint information in their decisions concerning affected pregnancies. Developing Cures for Inherited Disorders Research programs to locate inherited disorders on the chromosomes depend on the information contained in DNA fingerprints. By studying the DNA fingerprints of relatives who have a history of some particular disorder, or by comparing large groups of people with and without the disorder, it is possible to identify DNA patterns associated with the disease in question. This work is a necessary first step in designing an eventual genetic cure for these disorders. Biological Evidence FBI and police labs around the U.S. have begun to use DNA fingerprints to link suspects to biological evidence - blood or semen stains, hair, or items of clothing - found at the scene of a crime. Since 1987, hundreds of cases have been decided with the assistance of DNA fingerprint evidence. Another important use of DNA fingerprints in the court system is to establish paternity in custody and child support litigation. In these applications, DNA fingerprints bring an unprecedented, nearly perfect accuracy to the determination. Personal Identification Because every organ or tissue of an individual contains the same DNA fingerprint, the U.S. armed services have just begun a program to collect DNA fingerprints from all personnel for use later, in case they are needed to identify casualties or persons missing in action. The DNA method will be far superior to the dogtags, dental records, and blood typing strategies currently in use.

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FIRST "SYNTHETIC CELL"DEVELOPED

A team of US researchers, led by biologist Dr Craig Venter, has developed the first synthetic living cell in a laboratory.
The "landmark" study will play a crucial role in the field of genomics. It will help in the creation of artificial organisms for tasks including making vaccines or cleaning up pollution.
However, experts have warned that synthetic life could also pose potential dangers, as it could lead to terrifying biological weapons. This was demonstrated by Mary Shelley in her famous novel.

By breathing life into a bacterium using genes assembled in the laboratory, maverick genetics entrepreneur Dr Venter realised a 15-year dream.
The researchers "re-booted" a simple microbe by transplanting into it a set of genetic code sequences. The findings were published in the journal Science.
They copied the genome from the blueprint contained in Mycoplasma mycoides, a simple bacterium that infects cattle and goats.
After first constructing short strands of DNA, the scientists used yeast cells as natural factory assembly lines.
The sequence was built in a step-by-step process. DNA repair systems in the yeast attached the pieces together, gradually lengthening the strands to finish up with a chromosome more than a million "letters" of genetic code long.
The final test came when the completed chromosome was transplanted into another bacterium, Mycoplasma capricolum, replacing its native DNA.
After a failed first attempt, the scientists brought the cells to life. Driven by the new genome, the bacteria took on the appearance and behaviour of M. mycoides, generating different proteins and multiplying.

With a breakthrough that would make Dr Frankenstein proud, scientists in the US have pushed the boundaries of modern science by successfully implanting a synthetic genome into an emptied bacterium cell.

Discovery Channel will be exploring this artificial life breakthrough in a dedicated show, Creating Synthetic Life, on Monday 7th June at 8pm (UK).

For the first time ever, scientists have created artificial life with an organism that's controlled entirely by man-made DNA.

The US based scientists, working at the J. Craig Venter Institute, used the tools of synthetic biology to install the artificial genome inside a host cell from which they had completely removed the DNA. This artificial genome invigorated the host cell, which then began to grow and reproduce.

There were a few problems. Several of the synthesized genes didn't work properly, but there is no doubt that artificial life was successfully created.

'This is the first synthetic cell that's been made,' said Venter. 'We call it synthetic because the cell is totally derived from a synthetic chromosome, made with four bottles of chemicals on a chemical synthesizer, starting with information in a computer.'

This is a sample player which may be cloned for specific "Generic Video" pages for fansites

How will this affect the human race?

J. Crag Venter has partnered with both a pharmaceutical company and a major oil and gas company in order to raise funding for further research into what can be done with this new-found breakthrough.

It is thought that Venter's creation of artificial life could allow scientists to create more useful bacteria that can reduce the cost and speed up the production of biofuels, vaccines and drugs.

What do you think? Is the J. Craig venter Institute playing God by creating artificial life? Has science gone a step too far or is this the gateway to a future of untold possibility?

MAN MADE CELL

FIRST ARTIFICIAL HUMAN CHROMOSOME

CLEVELAND (4/02/97) Artificial human chromosomes have been created for the first time. This feat will help scientists better understand what natural chromosomes do and how they do it, and could prove useful in gene therapy.

"This opens the door to a whole new avenue of research in chromosome biology and gene therapy," said Huntington F. Willard, Ph.D., the senior author of the study, and chairman of genetics at Case Western Reserve University School of Medicine and University Hospitals of Cleveland.

"While it's been known since the early years of this century that chromosomes carry genes, until now the complexity and size of normal chromosomes has limited our ability to analyze their structure and function. The synthetic microchromosome system now allows us to perform detailed studies on the nature of chromosomes -- essentially the next phase of the Human Genome Project which is to move from just mapping genes to actually understanding how they work and influence human disease."

Natural chromosomes are consist of hundreds or thousands of genes, along with specialized elements that are believed to be important for chromosomal stability and function. Telomeres, which consist of DNA and protein, are located at the ends of chromosomes, protecting them from damage. Centromeres are specialized regions of DNA that are essential for the proper control of chromosome distribution during cell division. Human centromeres are believed to consist of large segments of highly repetitive DNA, called alpha satellite DNA, which is thought to play a significant role in centromeric function.

"Our successful creation of functional centromeres and incorporation of them into artificial chromosomes were the critical achievements enabling the stability and normal behavior of the chromosomes throughout the cell cycle," noted Dr. Willard. He added that past attempts at producing synthetic chromosomes have failed because they lacked proper centromeres, and thus could not persist through multiple cell divisions.

The research team created artificial chromosomes from normal human material using combinatorial genetic techniques. The researchers first synthesized arrays of alpha satellite DNA, then introduced the resulting centromeric material into human cells in conjunction with telomeres and genomic DNA. Inside the cells, the independent elements assembled to form miniature chromosomes, or synthetic microchromosomes, that were structurally similar to human chromosomes, but contained less genetic material.

Analysis of the newly introduced artificial chromosomes demonstrated normal centromeric activity, genetic stability, and continued gene expression through repeated rounds of the cell cycle.

"Synthetic chromosomes have the potential to overcome a major stumbling block in gene therapy," said John J. Harrington, Ph.D., a postdoctoral fellow at Case Western Reserve University. "The characteristic stability of our synthetic chromosomes enables, for the first time, the potential long-term expression of therapeutic proteins in target tissues of patients treated using gene therapy."

The synthetic microchromosome remains independent within the host cell and functions essentially as an accessory chromosome. In contrast, most gene therapy systems currently under development utilize viral vectors, which often require the integration of the therapeutic gene into an existing chromosome and thus can result in chromosomal damage or interference with normal gene expression. Viral vectors can also induce immune responses that limit therapeutic efficacy. In addition, unlike other vectors, which lack many of the elements that control normal gene expression due to size constraints, the synthetic chromosomes could be engineered to contain all of the machinery necessary to promote and regulate the stable production of therapeutic proteins.

The next step will be to refine the system and begin building an efficient vehicle for the introduction and stable maintenance of therapeutic genes in human cells. This might ultimately provide treatments for a wide variety of genetic disorders."

The research was published in the April 1997 issue of Nature Genetics.

JUMPING GENES ACTIVE IN LUNG CANCER

As new technologies allow closer investigation of human genomes, scientists are discovering they vary more among individuals than previously thought, one example being the presence of transposons also known as jumping genes, which a new US study found to be suprisingly prevalent in human genomes and also very active in lung cancer genomes.

Researchers at the University of Maryland (UM) School of Medicine in Baltimore, and colleagues from other research centers in the US, have conducted one of the first investigations of jumping genes, self-replicating bits of DNA that copy a section of genome then insert themselves in another section at a different location. You can read about their findings online in the 25 June issue of the journal Cell.

As soon as scientists mapped the human genome, it was clear that it would vary among individuals, study author Dr Scott E. Devine, an associate professor at UM School of Medicine and a researcher at the school's Institute for Genome Sciences, said in a statement.

Devine explained that variation in the human genome "dictates why people look different from one another, why they have different susceptibilities to diseases and different lifespans."

"In this study, we're looking at transposons that insert themselves in new places in various genomes and disrupt the blueprint," he added.

To illustrate why it matters that we find out more about transposons, Devine likened the genome to an instruction manual for building an aircraft and said "imagine what would happen if you copied the page that describes passenger seats and inserted it into the section that describes jet engines."

"Transposons act something like this: they copy themselves and insert the copies into other areas of the human genome, areas that contain instructions for the complex machine that is the human body," said Devine, who started the study when he was a faculty member at Emory University School of Medicine in Atlanta.

"These areas and the instructions they contain may then become corrupted and hard to understand. This, in turn, can alter human traits or even cause human diseases," he explained.

Because transposons replicate themselves, it suggests that offspring have more of them in their genomes than their parents.

"If you have a child, the child could have one or more new copies of these transposons that you don't have," said Devine.

This is the feature that he and his colleagues investigated using new, next generation sequencing and informatics technologies that they had developed.

For this study they examined the genomes of 76 people and found transposons were surprisingly prevalent; they also found they were very active in lung cancer genomes.

Some transposons don't seem to have a serious impact on the human genome, but several dozen have been found that have caused enough disruption to human genes to cause disease.

"We think this is just the tip of the iceberg," said Devine.

In their Cell paper, the researchers describe how their new technologies enabled them to detect insertions of two abundant classes of transposons called Alu and L1, that current technologies are not capable of detecting, and show how such insertions are abundant in human populations.

They wrote that genome-wide analysis suggests that "altered DNA methylation" may be the reason for the high levels of "somatic L1" transposon insertions in lung cancer genomes.

They concluded that:

"Our data indicate that transposon-mediated mutagenesis is extensive in human genomes and is likely to have a major impact on human biology and diseases."

The transposons they found in lung cancer tumors have never been seen before and could be important for cancer research, said Devine, who suggested the jumping genes could actually be driving cancer or tumor progression.

http://learn.genetics.utah.edu/

MEDICALGENETICREASEARCH

Medical genetics seeks to understand how genetic variation relates to human health and disease.^[68] When searching for an unknown gene that may be involved in a disease, researchers commonly use genetic linkage and genetic pedigree charts to find the location on the genome associated with the disease. At the population level, researchers take advantage of Mendelian randomization to look for locations in the genome that are associated with diseases, a technique especially useful for multigenic traits not clearly defined by a single gene.^[69] Once a candidate gene is found, further research is often done on the same gene (called an orthologous gene) in model organisms. In addition to studying genetic diseases, the increased availability of genotyping techniques has led to the field of pharmacogenetics—studying how genotype can affect drug responses.^[70]

Individuals differ in their inherited tendency to develop cancer,^[71] and cancer is a genetic disease.^[72] The process of cancer development in the body is a combination of events. Mutations occasionally occur within cells in the body as they divide. While these mutations will not be inherited by any offspring, they can affect the behavior of cells, sometimes causing them to grow and divide more frequently. There are biological mechanisms that attempt to stop this process; signals are given to inappropriately dividing cells that should trigger cell death, but sometimes additional mutations occur that cause cells to ignore these messages. An internal process of natural selection occurs within the body and eventually mutations accumulate within cells to promote their own growth, creating a cancerous tumor that grows and invades various tissues of the body.

MODEL ORGANISMS

Although geneticists originally studied inheritance in a wide range of organisms, researchers began to specialize in studying the genetics of a particular subset of organisms. The fact that significant research already existed for a given organism would encourage new researchers to choose it for further study, and so eventually a few model organisms became the basis for most genetics research.^[67] Common research topics in model organism genetics include the study of gene regulation and the involvement of genes in development and cancer.

Organisms were chosen, in part, for convenience—short generation times and easy genetic manipulation made some organisms popular genetics research tools. Widely used model organisms include the gut bacterium Escherichia coli, the plant Arabidopsis thaliana, baker's yeast (Saccharomyces cerevisiae), the nematode Caenorhabditis elegans, the common fruit fly (Drosophila melanogaster), and the common house mouse (Mus musculus).

Mutations alter an organisms genotype and occasionally this causes different phenotypes to appear. Most mutations have little effect on an organism's phenotype, health, or reproductive fitness. Mutations that do have an effect are usually deleterious, but occasionally some can be beneficial. Studies in the fly Drosophila melanogaster suggest that if a mutation changes a protein produced by a gene, about 70 percent of these mutations will be harmful with the remainder being either neutral or weakly beneficial.^[60]

An evolutionary tree of eukaryotic organisms, constructed by comparison of several orthologous gene sequences

Population genetics studies the distribution of genetic differences within populations and how these distributions change over time.^[61] Changes in the frequency of an allele in a population is mainly influenced by natural selection, where a given allele provides a selective or reproductive advantage to the organism,^[62] as well as other factors such as genetic drift, artificial selection and migration.^[63]

Over many generations, the genomes of organisms can change significantly, resulting in the phenomenon of evolution. Selection for beneficial mutations can cause a species to evolve into forms better able to survive in their environment, a process called adaptation.^[64] New species are formed through the process of speciation, often caused by geographical separations that prevent populations from exchanging genes with each other.^[65] The application of genetic principles to the study of population biology and evolution is referred to as the modern synthesis.

By comparing the homology between different species genomes it is possible to calculate the evolutionary distance between them and when they may have diverged (called a molecular clock).^[66] Genetic comparisons are generally considered a more accurate method of characterizing the relatedness between species than the comparison of phenotypic characteristics.^{[citation needed]} The evolutionary distances between species can be used to form evolutionary trees – these trees represent the common descent and divergence of species over time, although they do not show the transfer of genetic material between unrelated species (known as horizontal gene transfer and most common in bacteria).

MUTATIONS

During the process of DNA replication, errors occasionally occur in the polymerization of the second strand. These errors, called mutations, can have an impact on the phenotype of an organism, especially if they occur within the protein coding sequence of a gene. Error rates are usually very low—1 error in every 10–100 million bases—due to the "proofreading" ability of DNA polymerases.^[56][57] (Without proofreading error rates are a thousand-fold higher; because many viruses rely on DNA and RNA polymerases that lack proofreading ability, they experience higher mutation rates.) Processes that increase the rate of changes in DNA are called mutagenic: mutagenic chemicals promote errors in DNA replication, often by interfering with the structure of base-pairing, while UV radiation induces mutations by causing damage to the DNA structure.^[58] Chemical damage to DNA occurs naturally as well, and cells use DNA repair mechanisms to repair mismatches and breaks in DNA—nevertheless, the repair sometimes fails to return the DNA to its original sequence.

In organisms that use chromosomal crossover to exchange DNA and recombine genes, errors in alignment during meiosis can also cause mutations.^[59] Errors in crossover are especially likely when similar sequences cause partner chromosomes to adopt a mistaken alignment; this makes some regions in genomes more prone to mutating in this way. These errors create large structural changes in DNA sequence—duplications, inversions or deletions of entire regions, or the accidental exchanging of whole parts between different chromosomes (called translocation).

GENEREGULATION

The genome of a given organism contains thousands of genes, but not all these genes need to be active at any given moment. A gene is expressed when it is being transcribed into mRNA (and translated into protein), and there exist many cellular methods of controlling the expression of genes such that proteins are produced only when needed by the cell. Transcription factors are regulatory proteins that bind to the start of genes, either promoting or inhibiting the transcription of the gene.^[52] Within the genome of Escherichia coli bacteria, for example, there exists a series of genes necessary for the synthesis of the amino acid tryptophan. However, when tryptophan is already available to the cell, these genes for tryptophan synthesis are no longer needed. The presence of tryptophan directly affects the activity of the genes—tryptophan molecules bind to the tryptophan repressor (a transcription factor), changing the repressor's structure such that the repressor binds to the genes. The tryptophan repressor blocks the transcription and expression of the genes, thereby creating negative feedback regulation of the tryptophan synthesis process.^[53]

Transcription factors bind to DNA, influencing the transcription of associated genes.

Differences in gene expression are especially clear within multicellular organisms, where cells all contain the same genome but have very different structures and behaviors due to the expression of different sets of genes. All the cells in a multicellular organism derive from a single cell, differentiating into variant cell types in response to external and intercellular signals and gradually establishing different patterns of gene expression to create different behaviors. As no single gene is responsible for the development of structures within multicellular organisms, these patterns arise from the complex interactions between many cells.

Within eukaryotes there exist structural features of chromatin that influence the transcription of genes, often in the form of modifications to DNA and chromatin that are stably inherited by daughter cells.^[54] These features are called "epigenetic" because they exist "on top" of the DNA sequence and retain inheritance from one cell generation to the next. Because of epigenetic features, different cell types grown within the same medium can retain very different properties. Although epigenetic features are generally dynamic over the course of development, some, like the phenomenon of paramutation, have multigenerational inheritance and exist as rare exceptions to the general rule of DNA as the basis for inheritance.^[55]

NATURE VERSUS NURTURE

Although genes contain all the information an organism uses to function, the environment plays an important role in determining the ultimate phenotype—a phenomenon often referred to as "nature vs. nurture." The phenotype of an organism depends on the interaction of genetics with the environment. One example of this is the case of temperature-sensitive mutations. Often, a single amino acid change within the sequence of a protein does not change its behavior and interactions with other molecules, but it does destabilize the structure. In a high temperature environment, where molecules are moving more quickly and hitting each other, this results in the protein losing its structure and failing to function. In a low temperature environment, however, the protein's structure is stable and functions normally. This type of mutation is visible in the coat coloration of Siamese cats, where a mutation in an enzyme responsible for pigment production causes it to destabilize and lose function at high temperatures.^[49] The protein remains functional in areas of skin that are colder—legs, ears, tail, and face—and so the cat has dark fur at its extremities.

Environment also plays a dramatic role in effects of the human genetic disease phenylketonuria.^[50] The mutation that causes phenylketonuria disrupts the ability of the body to break down the amino acid phenylalanine, causing a toxic build-up of an intermediate molecule that, in turn, causes severe symptoms of progressive mental retardation and seizures. If someone with the phenylketonuria mutation follows a strict diet that avoids this amino acid, however, they remain normal and healthy.

A popular method to determine how much role nature and nurture play is to study identical and fraternal twins or siblings of multiple birth.^{[citation needed]} Because identical siblings come from the same zygote they are genetically the same. Fraternal siblings however are as different genetically from one another as normal siblings. By comparing how often the twin of a set has the same disorder between fraternal and identical twins, scientists can see if there is more of a nature or nurture effect. One famous example of a multiple birth study includes the Genain quadruplets, who were identical quadruplets all diagnosed with schizophrenia.^[51]

Genes generally express their functional effect through the production of proteins, which are complex molecules responsible for most functions in the cell. Proteins are chains of amino acids, and the DNA sequence of a gene (through RNA intermediate) is used to produce a specific protein sequence. This process begins with the production of an RNA molecule with a sequence matching the gene's DNA sequence, a process called transcription.

This messenger RNA molecule is then used to produce a corresponding amino acid sequence through a process called translation. Each group of three nucleotides in the sequence, called a codon, corresponds to one of the twenty possible amino acids in protein – this correspondence is called the genetic code.^[44] The flow of information is unidirectional: information is transferred from nucleotide sequences into the amino acid sequence of proteins, but it never transfers from protein back into the sequence of DNA—a phenomenon Francis Crick called the central dogma of molecular biology.^[45]

A single amino acid change causes hemoglobin to form fibers.

The specific sequence of amino acids results in a unique three-dimensional structure for that protein, and the three-dimensional structures of protein are related to their function.^[46][47] Some are simple structural molecules, like the fibers formed by the protein collagen. Proteins can bind to other proteins and simple molecules, sometimes acting as enzymes by facilitating chemical reactions within the bound molecules (without changing the structure of the protein itself). Protein structure is dynamic; the protein hemoglobin bends into slightly different forms as it facilitates the capture, transport, and release of oxygen molecules within mammalian blood.

The dynamic structure of hemoglobin is responsible for its ability to transport oxygen within mammalian blood.

A single nucleotide difference within DNA can cause a single change in the amino acid sequence of a protein. Because protein structures are the result of their amino acid sequences, some changes can dramatically change the properties of a protein by destabilizing the structure or changing the surface of the protein in a way that changes its interaction with other proteins and molecules. For example, sickle-cell anemia is a human genetic disease that results from a single base difference within the coding region for the β-globin section of hemoglobin, causing a single amino acid change that changes hemoglobin's physical properties.^[48] Sickle-cell versions of hemoglobin stick to themselves, stacking to form fibers that distort the shape of red blood cells carrying the protein. These sickle-shaped cells no longer flow smoothly through blood vessels, having a tendency to clog or degrade, causing the medical problems associated with this disease.

Some genes are transcribed into RNA but are not translated into protein products—these are called non-coding RNA molecules. In some cases, these products fold into structures which are involved in critical cell functions (e.g. ribosomal RNA and transfer RNA). RNA can also have regulatory effect through hybridization interactions with other RNA molecules (e.g. microRNA).

Discrete inheritance and Mendel's laws

At its most fundamental level, inheritance in organisms occurs by means of discrete traits, called genes.^[24] This property was first observed by Gregor Mendel, who studied the segregation of heritable traits in pea plants.^[9][25] In his experiments studying the trait for flower color, Mendel observed that the flowers of each pea plant were either purple or white – and never an intermediate between the two colors. These different, discrete versions of the same gene are called alleles.

In the case of pea, which is a diploid species, each individual plant has two alleles of each gene, one allele inherited from each parent.^[26] Many species, including humans, have this pattern of inheritance. Diploid organisms with two copies of the same allele of a given gene are called homozygous at that gene locus, while organisms with two different alleles of a given gene are called heterozygous.

The set of alleles for a given organism is called its genotype, while the observable traits of the organism are called its phenotype. When organisms are heterozygous at a gene, often one allele is called dominant as its qualities dominate the phenotype of the organism, while the other allele is called recessive as its qualities recede and are not observed. Some alleles do not have complete dominance and instead have incomplete dominance by expressing an intermediate phenotype, or codominance by expressing both alleles at once.^[27]

When a pair of organisms reproduce sexually, their offspring randomly inherit one of the two alleles from each parent. These observations of discrete inheritance and the segregation of alleles are collectively known as Mendel's first law or the Law of Segregation.

[edit] Notation and diagrams

Genetic pedigree charts help track the inheritance patterns of traits.

Geneticists use diagrams and symbols to describe inheritance. A gene is represented by a letter (or letters)—the capitalized letter represents the dominant allele and the recessive is represented by lowercase.^[28] Often a "+" symbol is used to mark the usual, non-mutant allele for a gene.^{[citation needed]}

In fertilization and breeding experiments (and especially when discussing Mendel's laws) the parents are referred to as the "P" generation and the offspring as the "F1" (first filial) generation. When the F1 offspring mate with each other, the offspring are called the "F2" (second filial) generation. One of the common diagrams used to predict the result of cross-breeding is the Punnett square.

When studying human genetic diseases, geneticists often use pedigree charts to represent the inheritance of traits.^[29] These charts map the inheritance of a trait in a family tree.

[edit] Interactions of multiple genes

Human height is a complex genetic trait. Francis Galton's data from 1889 shows the relationship between offspring height as a function of mean parent height. While correlated, remaining variation in offspring heights indicates environment is also an important factor in this trait.

Organisms have thousands of genes, and in sexually reproducing organisms assortment of these genes are generally independent of each other. This means that the inheritance of an allele for yellow or green pea color is unrelated to the inheritance of alleles for white or purple flowers. This phenomenon, known as "Mendel's second law" or the "Law of independent assortment", means that the alleles of different genes get shuffled between parents to form offspring with many different combinations.(Some genes do not assort independently, demonstrating genetic linkage, a topic discussed later in this article.)

Often different genes can interact in a way that influences the same trait. In the Blue-eyed Mary (Omphalodes verna), for example, there exists a gene with alleles that determine the color of flowers: blue or magenta. Another gene, however, controls whether the flowers have color at all or are white. When a plant has two copies of this white allele, its flowers are white—regardless of whether the first gene has blue or magenta alleles. This interaction between genes is called epistasis, with the second gene epistatic to the first.^[30]

Many traits are not discrete features (e.g. purple or white flowers) but are instead continuous features (e.g. human height and skin color). These complex traits are the product of many genes.^[31] The influence of these genes is mediated, to varying degrees, by the environment an organism has experienced. The degree to which an organism's genes contribute to a complex trait is called heritability.^[32] Measurement of the heritability of a trait is relative—in a more variable environment, the environment has a bigger influence on the total variation of the trait. For example, human height is a complex trait with a heritability of 89% in the United States. In Nigeria, however, where people experience a more variable access to good nutrition and health care, height has a heritability of only 62%.^[33]

[edit] Molecular basis for inheritance

[edit] DNA and chromosomes

Main articles: DNA and Chromosome

The molecular structure of DNA. Bases pair through the arrangement of hydrogen bonding between the strands.

The molecular basis for genes is deoxyribonucleic acid (DNA). DNA is composed of a chain of nucleotides, of which there are four types: adenine (A), cytosine (C), guanine (G), and thymine (T). Genetic information exists in the sequence of these nucleotides, and genes exist as stretches of sequence along the DNA chain.^[34] Viruses are the only exception to this rule—sometimes viruses use the very similar molecule RNA instead of DNA as their genetic material.^[35]

DNA normally exists as a double-stranded molecule, coiled into the shape of a double-helix. Each nucleotide in DNA preferentially pairs with its partner nucleotide on the opposite strand: A pairs with T, and C pairs with G. Thus, in its two-stranded form, each strand effectively contains all necessary information, redundant with its partner strand. This structure of DNA is the physical basis for inheritance: DNA replication duplicates the genetic information by splitting the strands and using each strand as a template for synthesis of a new partner strand.^[36]

Genes are arranged linearly along long chains of DNA sequence, called chromosomes. In bacteria, each cell usually contains a single circular chromosome, while eukaryotic organisms (which includes plants and animals) have their DNA arranged in multiple linear chromosomes. These DNA strands are often extremely long; the largest human chromosome, for example, is about 247 million base pairs in length.^[37] The DNA of a chromosome is associated with structural proteins that organize, compact, and control access to the DNA, forming a material called chromatin; in eukaryotes, chromatin is usually composed of nucleosomes, repeating units of DNA wound around a core of histone proteins.^[38] The full set of hereditary material in an organism (usually the combined DNA sequences of all chromosomes) is called the genome.

While haploid organisms have only one copy of each chromosome, most animals and many plants are diploid, containing two of each chromosome and thus two copies of every gene.^[26] The two alleles for a gene are located on identical loci of sister chromatids, each allele inherited from a different parent.

Walther Flemming's 1882 diagram of eukaryotic cell division. Chromosomes are copied, condensed, and organized. Then, as the cell divides, chromosome copies separate into the daughter cells.

An exception exists in the sex chromosomes, specialized chromosomes many animals have evolved that play a role in determining the sex of an organism.^[39] In humans and other mammals, the Y chromosome has very few genes and triggers the development of male sexual characteristics, while the X chromosome is similar to the other chromosomes and contains many genes unrelated to sex determination. Females have two copies of the X chromosome, but males have one Y and only one X chromosome—this difference in X chromosome copy numbers leads to the unusual inheritance patterns of sex-linked disorders.

[edit] Reproduction

Main articles: Asexual reproduction and Sexual reproduction

When cells divide, their full genome is copied and each daughter cell inherits one copy. This process, called mitosis, is the simplest form of reproduction and is the basis for asexual reproduction. Asexual reproduction can also occur in multicellular organisms, producing offspring that inherit their genome from a single parent. Offspring that are genetically identical to their parents are called clones.

Eukaryotic organisms often use sexual reproduction to generate offspring that contain a mixture of genetic material inherited from two different parents. The process of sexual reproduction alternates between forms that contain single copies of the genome (haploid) and double copies (diploid).^[26] Haploid cells fuse and combine genetic material to create a diploid cell with paired chromosomes. Diploid organisms form haploids by dividing, without replicating their DNA, to create daughter cells that randomly inherit one of each pair of chromosomes. Most animals and many plants are diploid for most of their lifespan, with the haploid form reduced to single cell gametes.

Although they do not use the haploid/diploid method of sexual reproduction, bacteria have many methods of acquiring new genetic information. Some bacteria can undergo conjugation, transferring a small circular piece of DNA to another bacterium.^[40] Bacteria can also take up raw DNA fragments found in the environment and integrate them into their genome, a phenomenon known as transformation.^[41] These processes result in horizontal gene transfer, transmitting fragments of genetic information between organisms that would be otherwise unrelated.

[edit] Recombination and linkage

Main articles: Chromosomal crossover and Genetic linkage

Thomas Hunt Morgan's 1916 illustration of a double crossover between chromosomes

The diploid nature of chromosomes allows for genes on different chromosomes to assort independently during sexual reproduction, recombining to form new combinations of genes. Genes on the same chromosome would theoretically never recombine, however, were it not for the process of chromosomal crossover. During crossover, chromosomes exchange stretches of DNA, effectively shuffling the gene alleles between the chromosomes.^[42] This process of chromosomal crossover generally occurs during meiosis, a series of cell divisions that creates haploid cells.

The probability of chromosomal crossover occurring between two given points on the chromosome is related to the distance between the points. For an arbitrarily long distance, the probability of crossover is high enough that the inheritance of the genes is effectively uncorrelated. For genes that are closer together, however, the lower probability of crossover means that the genes demonstrate genetic linkage – alleles for the two genes tend to be inherited together. The amounts of linkage between a series of genes can be combined to form a linear linkage map that roughly describes the arrangement of the genes along the chromosome.^[43]

Although the science of genetics began with the applied and theoretical work of Gregor Mendel in the mid-1800s, other theories of inheritance preceded Mendel. A popular theory during Mendel's time was the concept of blending inheritance: the idea that individuals inherit a smooth blend of traits from their parents. Mendel's work disproved this, showing that traits are composed of combinations of distinct genes rather than a continuous blend. Another theory that had some support at that time was the inheritance of acquired characteristics: the belief that individuals inherit traits strengthened by their parents. This theory (commonly associated with Jean-Baptiste Lamarck) is now known to be wrong—the experiences of individuals do not affect the genes they pass to their children.^[7] Other theories included the pangenesis of Charles Darwin (which had both acquired and inherited aspects) and Francis Galton's reformulation of pangenesis as both particulate and inherited.^[8]

[edit] Mendelian and classical genetics

The modern science of genetics traces its roots to Gregor Johann Mendel, a German-Czech Augustinian monk and scientist who studied the nature of inheritance in plants. In his paper "Versuche über Pflanzenhybriden" ("Experiments on Plant Hybridization"), presented in 1865 to the Naturforschender Verein (Society for Research in Nature) in Brünn, Mendel traced the inheritance patterns of certain traits in pea plants and described them mathematically.^[9] Although this pattern of inheritance could only be observed for a few traits, Mendel's work suggested that heredity was particulate, not acquired, and that the inheritance patterns of many traits could be explained through simple rules and ratios.

The importance of Mendel's work did not gain wide understanding until the 1890s, after his death, when other scientists working on similar problems re-discovered his research. William Bateson, a proponent of Mendel's work, coined the word genetics in 1905.^[10][11] (The adjective genetic, derived from the Greek word genesis—γένεσις, "origin" and that from the word genno—γεννώ, "to give birth", predates the noun and was first used in a biological sense in 1860.)^[12] Bateson popularized the usage of the word genetics to describe the study of inheritance in his inaugural address to the Third International Conference on Plant Hybridization in London, England, in 1906.^[13]

After the rediscovery of Mendel's work, scientists tried to determine which molecules in the cell were responsible for inheritance. In 1910, Thomas Hunt Morgan argued that genes are on chromosomes, based on observations of a sex-linked white eye mutation in fruit flies.^[14] In 1913, his student Alfred Sturtevant used the phenomenon of genetic linkage to show that genes are arranged linearly on the chromosome.^[15]

Morgan's observation of sex-linked inheritance of a mutation causing white eyes in Drosophila led him to the hypothesis that genes are located upon chromosomes.

[edit] Molecular genetics

Although genes were known to exist on chromosomes, chromosomes are composed of both protein and DNA—scientists did not know which of these is responsible for inheritance. In 1928, Frederick Griffith discovered the phenomenon of transformation (see Griffith's experiment): dead bacteria could transfer genetic material to "transform" other still-living bacteria. Sixteen years later, in 1944, Oswald Theodore Avery, Colin McLeod and Maclyn McCarty identified the molecule responsible for transformation as DNA.^[16] The Hershey-Chase experiment in 1952 also showed that DNA (rather than protein) is the genetic material of the viruses that infect bacteria, providing further evidence that DNA is the molecule responsible for inheritance.^[17]

James D. Watson and Francis Crick determined the structure of DNA in 1953, using the X-ray crystallography work of Rosalind Franklin and Maurice Wilkins that indicated DNA had a helical structure (i.e., shaped like a corkscrew).^[18][19] Their double-helix model had two strands of DNA with the nucleotides pointing inward, each matching a complementary nucleotide on the other strand to form what looks like rungs on a twisted ladder.^[20] This structure showed that genetic information exists in the sequence of nucleotides on each strand of DNA. The structure also suggested a simple method for duplication: if the strands are separated, new partner strands can be reconstructed for each based on the sequence of the old strand.

Although the structure of DNA showed how inheritance works, it was still not known how DNA influences the behavior of cells. In the following years, scientists tried to understand how DNA controls the process of protein production. It was discovered that the cell uses DNA as a template to create matching messenger RNA (a molecule with nucleotides, very similar to DNA). The nucleotide sequence of a messenger RNA is used to create an amino acid sequence in protein; this translation between nucleotide and amino acid sequences is known as the genetic code.

With this molecular understanding of inheritance, an explosion of research became possible. One important development was chain-termination DNA sequencing in 1977 by Frederick Sanger: This technology allows scientists to read the nucleotide sequence of a DNA molecule.^[21] In 1983, Kary Banks Mullis developed the polymerase chain reaction, providing a quick way to isolate and amplify a specific section of a DNA from a mixture.^[22] Through the pooled efforts of the Human Genome Project and the parallel private effort by Celera Genomics, these and other techniques culminated in the sequencing of the human genome in 2003.^[23]

GENETICS

This article is about the general scientific term. For the scientific journal, see Genetics (journal).

P

see Introduction to genetics.

DNA, the molecular basis for inheritance. Each strand of DNA is a chain of nucleotides, matching each other in the center to form what look like rungs on a twisted ladder.

Genetics (from Ancient Greek γενετικός genetikos, “genitive” and that from γένεσις genesis, “origin”^[1][2][3]), a discipline of biology, is the science of heredity and variation in living organisms.^[4][5] The fact that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding. However, the modern science of genetics, which seeks to understand the process of inheritance, only began with the work of Gregor Mendel in the mid-nineteenth century.^[6] Although he did not know the physical basis for heredity, Mendel observed that organisms inherit traits via discrete units of inheritance, which are now called genes.

Genes correspond to regions within DNA, a molecule composed of a chain of four different types of nucleotides—the sequence of these nucleotides is the genetic information organisms inherit. DNA naturally occurs in a double stranded form, with nucleotides on each strand complementary to each other. Each strand can act as a template for creating a new partner strand—this is the physical method for making copies of genes that can be inherited.

The sequence of nucleotides in a gene is translated by cells to produce a chain of amino acids, creating proteins—the order of amino acids in a protein corresponds to the order of nucleotides in the gene. This relationship between nucleotide sequence and amino acid sequence is known as the genetic code. The amino acids in a protein determine how it folds into a three-dimensional shape; this structure is, in turn, responsible for the protein's function. Proteins carry out almost all the functions needed for cells to live. A change to the DNA in a gene can change a protein's amino acids, changing its shape and function: this can have a dramatic effect in the cell and on the organism as a whole.

Although genetics plays a large role in the appearance and behavior of organisms, it is the combination of genetics with what an organism experiences that determines the ultimate outcome. For example, while genes play a role in determining an organism's size, the nutrition and other conditions it experiences after inception also have a large effect.