genetics

Dictionary: ge·net·ics   (jə-nĕt'ĭks)

1. (used with a sing. verb) The branch of biology that deals with heredity, especially the mechanisms of hereditary transmission and the variation of inherited characteristics among similar or related organisms.
2. (used with a pl. verb) The genetic constitution of an individual, group, or class.

Concept

Genetics is the area of biological study concerned with heredity and with the variations between organisms that result from it. It demands an understanding of numerous terms, such as DNA (deoxyribonucleic acid), a molecule in all cells that contains blueprints for genetic inheritance; genes, units of information about particular heritable traits, which are made from DNA; and chromosomes, DNA-containing bodies, located in the cells of most living things, that hold most of the organism's genes. The vocabulary of genetics goes far beyond these three terms, as we shall see, but these are the core concepts. Among the areas in which genetics is applied is forensic science, or the application of science to matters of law—specifically, through "DNA fingerprinting," whereby samples of skin, blood, semen, and other materials can be used to prove or disprove a suspect's innocence. Another fascinating application of genetics is the Human Genome Project, an effort whose goals include the location and identification of every gene in the human body.

How It Works

Genetics and Heredity

Genetics and heredity, the subject of another essay in this book, are closely related ideas. Whereas heredity is the transmission of genetic characteristics from ancestor to descendant through the genes, genetics is concerned with hereditary traits passed down from one generation to the next. It is very hard, if not impossible, to separate the two concepts completely, yet the entire body of knowledge encompassed by these topics is so large and so complex that it is best to separate them as much as possible. For this reason, the Heredity essay is concerned with such issues as how traits are passed on and why they appear in a particular generation but not another. That essay addresses the topics of alleles, dominant and recessive genes, and so on. It also briefly discusses the history of studies in areas that encompass genetics, heredity, and the mechanics thereof. In general, the Heredity essay is concerned with the larger patterns of inheritance over the generations, while the present one examines inheritance at a level smaller than the microscopic—that is, from the molecular or biochemical level.

Somatic and Germ Cells

Heredity begins with the cell, the smallest basic unit of all life. The information for heredity is carried within the cell nucleus, which is the control center not only in physical terms (it is usually located near the middle of the cell) but also because it contains the chromosomes. Within these threadlike structures is the genetic information organized in DNA molecules.

There are two basic types of cell in a multicellular organism: somatic, or body, cells, and germ, or reproductive, cells. The somatic cells are the primary components of most organisms, making up everything except some of the the cells in reproductive organs. The somatic cells of humans have 23 pairs of chromosomes, or 46 chromosomes overall, and are thus known as diploid cells. As the cells grow, they reproduce themselves by a process called mitosis, whereby a diploid cell splits to produce new diploids, each of which is a replica of the original. Thus cells grow and are replaced, making possible the formation of specific tissues and organs, such as muscles and nerves. Without mitosis, an organism's cells would not regenerate, resulting not only in cell death but possibly even the death of the entire organism. Mitosis is also the means of reproduction for organisms that reproduce asexually (see Reproduction).

A germ cell, by contrast, undergoes a process of cell division known as meiosis, whereby it becomes a haploid cell—a cell with half the basic number of chromosomes, which for a human would be 23 unpaired chromosomes. The sperm cells in a male and the egg cells in a female are both haploid germ cells: each contains only 23 chromosomes, and each is prepared to form a new diploid by fusion with another haploid. Sperm cells and egg cells are known as gametes, mature male or female germ cells that possess a haploid set of chromosomes and are prepared to form a new diploid by undergoing fusion with a haploid gamete of the opposite sex.

When egg and sperm fuse, they form a zygote, in which the diploid chromosome number is restored, with the zygote possessing the same chromosomes as both the sperm and the egg. This cell carries all the genetic information needed to grow into an embryo and eventually a full-grown human, with the specific traits and attributes passed on by the parents. Not all offspring of the same parents are the same, of course, and this is because the sperm cells and egg cells vary in their genetic codes—that is, in their DNA blueprints.

The Dna Blueprint

To understand genes and their biological function in heredity, it is necessary to understand the chemical makeup and structure of DNA. The complete DNA molecule often is referred to as the blueprint for life, because it carries all the instructions, in the form of genes, for the growth and functioning of organisms. This fundamental molecule is similar in appearance to a spiral staircase, which also is called a double helix. The sides of the DNA ladder are made up of alternate sugar and phosphate molecules, like links in a chain. The rungs, or steps, of DNA are made from a combination of four different chemical bases. Two of these, adenine and guanine, are known as purines, and the other two, cytosine and thymine, are pyrimidines. The four letters designating these bases—A, G, C, and T—are the alphabet of the genetic code, and each rung of the DNA molecule is made up of a combination of two of these letters.

Dna Sequences

In this genetic code A always combines with T and C with G, to form what is called a base pair. Specific sequences of these base pairs make up the genes. Although a four-letter alphabet may seem rather small for constructing the extensive vocabulary that defines the myriad life-forms on Earth, in practice, the sequences of these base pairs make for almost limitless combinations. For any sequence, there are four possibilities as to the first two letters (AT, TA, CG, or GC) and four more possibilities for the second two letters. Thus, just for a four-letter sequence, there are 16 possibilities, and for each pair of letters added to the sequence, the total is multiplied by four. Given the long strings of base pairs that form DNA sequences, the numbers can be extremely large.

The more complex an organism, from bacteria to humans, the more rungs, or genetic sequences, appear on the ladder. The entire genetic makeup of a human, for example, may contain three billion base pairs, with the average gene unit being 2,000-200,000 base pairs long. Each one of these combinations has a different meaning, providing the code not only for the type of organism but also for specific traits, such as brown hair and blue eyes, dimples, detached earlobes, and so on and on. Except for identical twins, no two humans have exactly the same genetic information.

Dna Replication, Protein Synthesis, and Rna

Genetic information is duplicated during the process of DNA replication, which is initiated by proteins in the cells. To produce identical genetic information during cell mitosis, the DNA hydrogen bonds between the two strands arebroken, splitting the DNA in half lengthwise. This process begins a few hours before the initiation of cell mitosis, and once it is completed, each half of the DNA ladder is capable of forming a new DNA molecule with an identical genetic code. It can do this because of specific chemical catalysts (a substance that enables a chemical reaction without taking part in it) that help synthesize the complementary strand.

Catalysts formed from proteins are known as enzymes, and the functioning of specific cells and organisms is conducted by enzymes synthesized by the cells. Cells contain hundreds of different proteins, complex molecules that make up more than half of all solid body tissues and control most biological processes within and among these tissues. A cell functions in accordance with the particular protein—one of thousands of different types—it contains. It is the genetic base-pair sequence in DNA that determines, or "codes for," the specific arrangement of amino acids to build particular proteins.

Since the sites of protein production lie outside the cell nucleus, coded messages pass from the DNA in the nucleus to the cytoplasm, the material inside the cell that is external to the nucleus. This transfer of messages is achieved by RNA, or ribonucleic acid, and specifically by messenger RNA, or mRNA. Other types of RNA molecules are involved in linking the amino-acids together in a sequence form to shape the protein. (For more about amino acids, proteins, and enzymes, see the respective essays devoted to each subject.)

Mutation

Once a protein has been created for a specific function, it cannot be changed. This is why the theory of acquired characteristics (the idea that changes in an organism's overall anatomy, as opposed to changes in its DNA, can be passed on to offspring) is a fallacy. People may have genes that make it easier for them to acquire certain traits, such as larger muscles or the ability to play the piano through exercise or practice, respectively, but the traits themselves, if they are acquired during the life of the individual and are not encoded in the DNA, are not heritable.

There is only one way in which changes that take place during the life of an organism can be passed on to its offspring, and that is if those changes are encoded in the organism's DNA. This is known as mutation. Suppose lung cancer develops in a man as a result of smoking; unless a tendency to cancer is already a part of his genetic makeup, he cannot genetically pass the disease on to his unborn children. But if the tobacco has acted as a mutagen, a substance that brings about mutation, it is possible that his DNA can be altered in such a way as to pass on either the tendency toward lung cancer or some other characteristic.

Because DNA is extremely stable chemically, it rarely mutates, or experiences an alteration in its physical structure, during replication. But because there are so many strands of DNA in the world, and so much material in the strands, mutation is bound to happen eventually—and, to an extent, at least, this is a good thing. Mutation is the engine that drives evolution, and a certain amount of genetic variation is necessary if species are to adapt by natural selection to a changing environment. If it were not for mutation, neither humans nor the many millions of other species that exist would ever have appeared.

Mutation often occurs when chromosome segments from two parents physically exchange places with each other during the process of meiosis. This is known as genetic recombination. Genes also can change by mutations in the DNA molecule, which take place when a mutagen alters the chemical or physical makeup of DNA. The mutations that result are of two types, corresponding to the two basic varieties of cell: somatic mutations, which occur solely within the affected individual, and germinal mutations, which happen in the DNA of germ cells, producing altered genes that may be passed on to the next generation.

The odd thing about mutations is that while most of them are harmful, the few that are beneficial are, as we have noted, the driving force behind the evolution of life-forms that successfully adapt to their environments. Thus, while most germinal mutations bring about congenital disorders (birth defects) ranging from physical abnormalities to deficiencies in body or mind to diseases, every once in a while a germinal mutation results in an improvement, such as a change in body coloring that acts as camouflage. If the trait improves an individual organism's chances for survival within a particular environment, it may become a permanent trait of the species, because the offspring with this gene have a greater chance of survival and thus will pass on the trait to succeeding generations. (For more about mutation, see the essay by that title. See also Evolution for a discussion of the role played by mutation and natural selection in the evolution of species.)

Real-Life Applications

The Genetics Revolution

In the modern world genetics plays a part in more dramatic breakthroughs than any other field of biological study. These breakthroughs have an impact in a wide variety of areas, from curing diseases to growing better vegetables to catching criminals. The field of genetics is in the midst of a revolution, and at the center of this exciting (and, to some minds, terrifying) phenomenon is the realm of genetic engineering: the alteration of genetic material by direct intervention in genetic processes. In agriculture, for instance, genes are transplanted from one organism to another to produce what are known as transgenic animals or plants. This approach has been used to reduce the amount of fat in cattle raised for meat or to increase proteins in the milk produced by dairy cattle. Fruits and vegetables also have been genetically engineered so that they do not bruise easily or have a longer shelf life.

Not all of the work in genetics is genetic engineering per se; in the realm of law, for instance, the most important application of genetics is genetic fingerprinting. A genetic fingerprint is a sample of a person's DNA that is detailed enough to distinguish it from the DNA of all others. The genetic fingerprint can be used to identify whether a man is the father of a particular child (i.e., to determine paternity), and it can be applied in the solving of crimes. If biological samples can be obtained from a crime scene—for example, skin under the fingernails of a murder victim, presumably the result of fighting against the assailant in the last few moments of life—it is possible to determine with a high degree of accuracy whether that sample came from a particular suspect. The use of DNA in forensic science is discussed near the conclusion of this essay.

The Revolution in Medicine

Some of the biggest strides in genetic engineering and related fields are taking place, not surprisingly, in the realm of medicine. Genetic engineering in the area of health is aimed at understanding the causes of disease and developing treatments for them: for example, recombinant DNA (a DNA sequence from one species that is combined with the DNA of another species) is being used to develop antibiotics, hormones, and other disease-preventing agents. Vaccines also have been genetically re-engineered to trigger an immune response that will protect against specific diseases. One approach is to remove genetic material from a diseased organism, thus making the material weaker and initiating an immune response without causing the disease. (See Immunity and Immunology for more about how vaccines work.)

Gene therapy is another outgrowth of genetics. The idea behind gene therapy is to introduce specific genes into the body either to correct a genetic defect or to enhance the body's capabilities to fight off disease and repair itself. Since many inherited or genetic diseases are caused by the lack of an enzyme or protein, scientists hope one day to treat the unborn child by inserting genes to provide the missing enzyme. (For more about inherited disorders, see the essays Disease, Noninfectious Diseases, and Mutation.)

The Human Genome Project

One of the most exciting developments in genetics is the initiation of the Human Genome Project, designed to provide a complete genetic map outlining the location and function of the 40,000 or so genes that are found in human cells. (A genome is all of the genetic material in the chromosomes of a particular organism.) With the completion of this map, genetic researchers will have easy access to specific genes, to study how the human body works and to develop therapies for diseases. Gene maps for other species of animals also are being developed.

The project had its origins in the 1990s, with the efforts of the United States Department of Energy (DOE) and the National Institutes of Health (NIH). The NIH connection is probably clear enough, but the DOE's involvement at first might seem strange. What, exactly, does genetics have to do with electricity, petroleum, and other concerns of the DOE? The answer is that the DOE grew out of agencies, among them the Atomic Energy Commission (AEC), established soon after the explosion of the two atomic bombs over Japan in 1945. Even at that early date, educated nonscientists understood that the radioactive fallout produced from nuclear weaponry can act as a mutagen; therefore, Congress instructed the AEC to undertake a broad study of genetics and mutation and the possible consequences of exposure to radiation and the chemical by-products of energy production.

Eventually, scientists in the AEC and, later, the DOE recognized that the best way to undertake such a study was to analyze the entire scope of the human genome. The project formally commenced on October 1, 1990, and is scheduled for completion in the middle of the first decade of the twenty-first century. Upon completion, the Human Genome Project will provide a vast store of knowledge and no doubt will lead to the curing of many diseases.

Still, there are many who question the Human Genome Project in particular, and genetic engineering in general, on ethical grounds, fearing that it could give scientists or governments too much power, unleash a Nazi-style eugenics (selective breeding) program, or result in horrible errors, such as the creation of deadly new diseases. In fact, it is impossible to search "genetic engineering" on the World Wide Web without coming across the Web sites of literally dozens and dozens of agencies, activist groups, and individuals opposed to genetic engineering and the mapping of the human genome. For more about the Human Genome Project, genetic engineering, and their opponents, see Genetic Engineering.

Genetics in Forensic Science

Forensic science, as we noted earlier, is the application of science to matters of law. It is based on the idea that a criminal always leaves behind some kind of material evidence that, through careful analysis, can be used to determine the identity of the perpetrator—and to exonerate someone falsely accused. Among those forms of material evidence of interest to forensic scientists working in the field of genetics are blood, semen, hair, saliva, and skin, all of which contain DNA that can be analyzed. In addition, there are areas of forensic science that rely on biological study, though not in the area of genetics: blood typing as well as the analysis of fingerprints or bite marks, both of which have patterns that are as unique to a single individual as DNA is.

One of the first detectives to use science, including biology and medicine, in solving crimes was a fictional character: Sherlock Holmes, whose creator, the British writer Sir Arthur Conan Doyle (1859-1930), happened to be a physician as well. The first full-fledged (and real) police practitioner of forensic science was the French police official Alphonse Bertillon (1853-1914), who developed an identification system that consisted of a photograph and 11 body measurements, including dimensions of the head, arms, legs, feet, hands, and so on, for each individual. Bertillon claimed that the likelihood of two people having the same measurements for all 11 traits was less than one in 250 million. In 1894 fingerprints, which were easier to use and more unique than body measurements, were added to the Bertillon system.

Fingerprints, unlike DNA, are unique to the individual; indeed, identical twins have the same DNA but different fingerprints. Mark Twain (1835-1910) could not have known this in 1894, when he published The Tragedy of Pudd'nhead Wilson, and the Comedy of Those Extraordinary Twins. Nonetheless, the story involves a murder committed by one man and blamed on his twin, who eventually is exonerated on the basis of fingerprint evidence—still a new concept at the time. In some situations, however, fingerprint evidence may be unavailable, and though law-enforcement agencies have developed extraordinary techniques for analyzing nearly invisible (i.e., latent) prints, sometimes this is still not enough.

The Simpson Case and the Controversy Over Dna Evidence

For example, in the infamous murder of Nicole Brown Simpson and Ron Goldman on June 12, 1994, fingerprint evidence would have been ineffective in the case against the suspect, the former football star and actor O. J. Simpson. Since Nicole Simpson was his ex-wife, the appearance of his prints at the scene of her murder in her Los Angeles home could be explained away easily, even though she had taken out a restraining order against her former husband (who she had accused of spousal abuse) some time before the murder. Rather than fingerprints, the prosecution in his murder trial used DNA evidence connecting blood at the crime scene with blood found in Simpson's vehicle. (Some of this blood was apparently his own, since he had mysterious cuts on his hands that he could not explain to police officers.)

A jury found Simpson not guilty on October 3, 1995, and jurors later claimed that the prosecution had failed to make a strong case using DNA evidence. Furthermore, they cited police contamination of the DNA evidence, which had been established in their minds by Simpson's defense team, as a cause for reasonable doubt concerning Simpson's guilt. In fact, assuming that the defense was fully justified in this claim, that would have meant only that the DNA samples would have been less (not more) likely to convict Simpson.

At the same time, a number of legitimate concerns regarding the use of DNA evidence were raised by experts for the defense in the Simpson trial. Samples can become contaminated and thus difficult to read; small samples are difficult for analysts to work with effectively; and results are often open to interpretation. Furthermore, the outcome of the Simpson case illustrates the fact that findings based on DNA evidence are not readily understood by non-specialists, and may not make the best basis for a case-particularly in one so fraught with controversy. The prosecution based its case almost entirely on extremely technical material, explained in excruciating detail by experts who had devoted their lives to studying areas that are far beyond the understanding of the average person. Attempting to wow the jurors with science, the prosecution instead seemed to create the impression that DNA evidence was some sort of hocus-pocus invented to frame an innocent man. Simpson went free, though the jury in a 1996 civil trial (which took a much simpler approach, eschewing complicated DNA testimony) found him guilty.

Dna Evidence Success Stories

Because of the Simpson case, the use of DNA evidence gained something of a bad name. Nonetheless, it has been successful in less high profile cases, beginning in 1986, when English police tracked down a rapist and murderer by collecting blood samples from some 2,000 men. One of them, named Colin Pitchfork, paid another man to provide a sample in his place. This attracted the attention of the police, who tested his DNA and found their man.

Since that time, DNA evidence has been used in more than 24,000 cases and has aided in the conviction of about 700 suspects. The DNA in such cases is not always obtained from a human subject. In the investigation of the May 1992 murder of Denise Johnson in Arizona, a homicide detective found two seed pods from a paloverde tree in the bed of a pickup truck owned by the suspect, Mark Bogan. The accused man admitted having known the victim but denied ever having been near the site where her body was found. It so happened that there was a paloverde tree at the site, and testing showed that the DNA in the pods on his truck bed matched that of the tree itself. Bogan became the first suspect ever convicted by a plant.

On the other hand, in some cases, DNA evidence has cleared a suspect falsely accused. Such was the case with Kerry Kotler, convicted in 1981 for rape, robbery, and burglary and sentenced to 25-50 years in jail. In 1988, Kotler began petitioning for DNA analysis, which subsequently showed that his DNA did not match that of the rapist, who had left a semen sample in the victim's underwear. Kotler was released in December 1992 and in March 1996 was awarded $1.5 million in damages for his wrongful imprisonment. The story does not end there, however. Kotler's case turned out to be one of the more bizarre in the annals of forensic DNA testing. Perhaps he did not commit the first rape, but a month after he received the damage award, he was on his way back to prison for the August 1995 rape of another victim. This time prosecutors showed that Kotler's semen matched samples taken from his victim's clothing—and to prove their case, they used DNA testing.

Where to Learn More

Department of Energy Human Genome Program (Web site). <http://www.ornl.gov/hgmis/>.

The DNA Files/National Public Radio (Web site). <http://www.dnafiles.org/>.

Fridell, Ron. DNA Fingerprinting: The Ultimate Identity. New York: Franklin Watts, 2001.

Genetics Education Center, University of Kansas Medical Center (Web site). <http://www.kumc.edu/gec/>.

Henig, Robin Marantz. The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, the Father of Genetics. Boston: Houghton Mifflin, 2000.

Lerner, K. Lee, and Brenda Wilmoth Lee. World of Genetics. Detroit: Gale Group, 2002.

National Human Genome Research Institute (Web site). <http://www.nhgri.nih.gov>.

Schwartz, Jeffrey H. Sudden Origins: Fossils, Genes, and the Emergence of Species. New York: John Wiley and Sons, 1999.

Tudge, Colin. The Impact of the Gene: From Mendel's Peas to Designer Babies. New York: Hill and Wang, 2001.

Virtual Library on Genetics, Oak Ridge National Laboratory (Web site). <http://www.ornl.gov/TechResources/Human_Genome/genetics.html>.

The science of biological inheritance, that is, the causes of the resemblances and differences among related individuals.

Genetics occupies a central position in biology, for essentially the same principles apply to all animals and plants, and understanding of inheritance is basic for the study of evolution and for the improvement of cultivated plants and domestic animals. It has also been found that genetics has much to contribute to the study of embryology, biochemistry, pathology, anthropology, and other subjects. See also Biochemistry; Embryology; Pathology; Physical anthropology.

Genetics may also be defined as the science that deals with the nature and behavior of the genes, the fundamental hereditary units. From this point of view, evolution is seen as the study of changes in the gene composition of populations, whereas embryology is the study of the effects of the genes on the development of the organism. See also Gene action; Population genetics.

The field of molecular genetics describes the basis of inheritance at the molecular level. It focuses on two general questions: how do genes specify the structure and function of organisms, and how are genes replicated and transmitted to successive generations? Both questions have been answered. Genes specify organismal structure and function according to a process described by the central dogma of molecular biology: DNA is made into messenger ribonucleic acid (mRNA), which specifies the structure of a protein; the mRNA molecule then serves as a template for protein synthesis, which is carried out by complex machinery that comprises a particle called a ribosome and special adapter RNA molecules called transfer RNA. See also Deoxyribonucleic acid (DNA); Ribonucleic acid (RNA); Ribosomes.

The structure of DNA provides a simple mechanism for genes to be faithfully reproduced: the specific interaction between the nucleotides means that each strand of the double helix carries the information for producing the other strand. See also Genetic code; Genetic engineering; Molecular biology; Mutation.

The science that deals with the origin of the characteristics of an individual.

The role of genetics in medicine and public health came to broad public consciousness quite dramatically in June 2000, when President Bill Clinton and Prime Minister Tony Blair jointly sponsored the announcement by government, academic, and industrial scientists that a "first draft" of the human genome sequence had been completed. Then, in early 2001, the announcement of the full sequencing and a revised estimate of the number of genes in the human genome was released. No doubt many people were mystified by the term "genome," even if they had some idea about what genes and proteins are. The genome is the complete set of genes of each individual in any species. In humans, there are an estimated 30,000 to 100,000 genes in the forty-six chromosomes of, essentially, all human cells. In early 2001, the same scientific groups reported a nearly complete sequence for the human genome, with an estimated 30,000 to 40,000 genes distributed on twenty-three pairs of chromosomes.

The Molecular Nature of Genes

DNA (deoxyribonucleic acid) molecules carry the code for genetic information and its transmission from one generation to the next. For decades it was thought that DNA was a most unlikely candidate for this role, due to its presumed simplicity (compared with proteins). DNA consists of a string of just four different nucleotide bases (A, T, G, C—for adenine, thymine, guanine, cytosine) held together by a sugar (deoxyribose)—phosphate backbone. In contrast, proteins are polypeptide chains of twenty different amino acids, offering much more variation for coding. In a classic experiment in 1944, scientists at the Rockefeller Institute in New York City working with bacteria that cause pneumococcal pneumonia showed that inherited transformation of the surface characteristics of the bacteria could be accomplished with DNA and not with protein.

In 1953, James Watson and Francis Crick, at Cambridge University in England, published the stunning hypothesis that two intertwined strands of DNA, running in opposite directions, could be joined in a double helix through hydrogen bonds linking the nucleotide bases in the specific combinations of A-T and G-C. This model was justified by available X-ray pictures of the molecular patterns of DNA. Linear sets of three nucleotide bases generate a "triplet code," with sixty-four combinations, more than enough to code for the twenty amino acids. We now know that the double helix of DNA can separate, through actions of enzymes that facilitate unwinding, so that one strand of the double-stranded DNA can be transcribed into messenger RNA (mRNA) molecules. The mRNA is then translated into polypeptides, which assume highly folded three-dimensional structures to function as enzymes, antibodies, and structural components of cells. Other RNA molecules are involved in supporting the formation of the polypeptides and in delivering the right amino acid to the growing polypeptide chain as directed by the triplet code in the mRNA.

This flow of information from DNA to RNA to protein is a general phenomenon throughout living organisms. There are exceptions, such as viruses (including HIV/AIDS [human immodeficiency virus/acquired immunodeficiency syndrome]) which use RNA as their genetic material. When these viruses infect human (or plant or animal) cells, they must first convert their RNA message into DNA to join the flow of information in the cell from DNA to RNA to protein. Similar "reverse transcription" can occur in cancer cells and during embryological development. Experimental conversion of mRNA to DNA is utilized very extensively to clone and sequence individual genes, key techniques in the field of biotechnology.

The Basis for Inheritance

Long DNA molecules are carried on structures called chromosomes in the nucleus inside each cell. Human chromosomes occur in pairs, one derived from the mother and one from the father in sexual reproduction. Humans have twenty-three pairs of chromosomes, of which twenty-two are similar in males and females. These are numbered 1 through 22, according to chromosome size (1 is the largest). One chromosome pair is different between females and males: XX in females (one X from each parent) and XY in males (X from the mother and Y from the father).

When ordinary cells divide (during fetal development, normal growth, and the regeneration of skin, other organs, and cells lining the lung, intestine, and uterus), the chromosomes must be duplicated and then be distributed to daughter cells so that every cell gets a full set of twenty-three pairs of chromosomes. When the chromosomes are duplicated, the DNA must be replicated, as well.

Egg-forming cells in the ovary and sperm-forming cells in the testes are unique. They are duplicated in a more complex pattern so that they contain only one each of the twenty-three pairs of chromosomes; when egg and sperm then combine, their aggregate of chromosomes is the expected twenty-three pairs.

Something else important can happen during duplication of chromosomes and replication of DNA. There may be recombination across the pairs of chromosomes between the DNA strands, so that genes (information) from the mother are combined at the molecular level with information from the father, and vice versa. Also, there may be mistakes. Mistakes in an individual gene occurring during replication, or when triggered by X-rays, ultraviolet radiation, or chemical reactions, are called "mutations." The complementary double-stranded structure of DNA is a defense against loss of information when DNA is damaged or broken; the damaged strand is repaired using the complementary strand to direct the repair. Mistakes that occur when chromosomes are duplicated can lead to translocations of part of one chromosome onto another, loss of a chromosome or part of a chromosome, or failure of separation of duplicated chromosomes (gaining a third copy of that chromosome, as in Down syndrome, where there are three copies of chromosome 21). In addition, some genes are actually carried outside the nucleus in the energy factories called mitochondria; these can be passed on only by the mother, in the egg cell, and are associated with certain diseases of muscle and brain.

Mapping Genes on Chromosomes

Very effective methods have been developed to identify which genes for specific traits or diseases are located on which chromosomes, and to pinpoint the location on the relevant chromosome. The smallest genes consist of only a few hundred bases of DNA; the largest known human gene, which is mutated in Duchenne muscular dystrophy, is 2 million base pairs in length. A surprising feature of all nonbacterial genes is their organization into "introns" and "exons." Introns are noncoding stretches of DNA within the gene which are transcribed into RNA but then spliced out before the RNA is translated into protein. There are also untranslated noncoding regions at each end of the gene. There are lots of signals built into the sequence of the DNA—for initiation, stopping, splicing, and other functions crucial to defining the genes in the lengthy DNA molecules; for regulating their expression as mRNA and proteins; and for coordinating regulation of related genes. Some genes have only a single exon; others have up to one hundred interruptions with introns. The reasons are still quite obscure.

Gene mapping before 1950 was limited to the X chromosome, deduced by mother-to-son transmission in pedigrees (diagrams of family histories) for X-linked diseases (e.g., hemophilia) or traits (e.g., color blindness). A few genes were located on abnormal chromosomes by careful clinical correlations. Improved chromosomal analyses permitted formation of double-stranded DNA between fluorescent-labeled probe DNA and the DNA in a particular chromosome. Another method used mouse/human hybrid cells with one each of the different human chromosomes—if a human gene could be detected in the presence of the mouse genes, that gene must be coded for on the single human chromosome present. Once one gene is located, another gene which is linked in transmission from generation to generation can be deduced to be on the same chromosome. For example, the gene for cystic fibrosis was placed near linked markers on chromosome 7. This is truly a needle-in-the-haystack approach, since there are some 30,000 to 40,000 genes, distributed on the 23 pairs of chromosomes.

Everything changed with the new methods of recombinant DNA and the polymerase chain reaction—a way to produce millions of copies of a particular DNA molecule isolated or synthesized in tiny amounts. Increasingly, genes are being identified without the benefit of an initial chromosomal localization. A scan of the entire genome (across all chromosomes) is performed in a search for linkage to fairly common variants of genes that serve as well-spaced markers, even without knowing their function. Many steps in this approach are now automated, thousands of samples can be processed, and powerful computer programs sift through hundreds or thousands of markers to find clues for localization of the presumed gene or genes for a disease. Segments of DNA from the suspected chromosomal region can be cloned into specialized vectors. Linking together all such fragments permits scientists to assemble the genome sequence of humans or of many other organisms (e.g., yeast, fruitfly, bacteria, earthworm, mouse). A much more complicated mapping process is helpful in locating multiple genes for complex diseases like diabetes, high blood pressure, or depression.

The Human Genome Project

According to Francis Collins, director of the National Human Genome Research Institute, "mapping the human genetic terrain may rank with the great expeditions of Lewis and Clark, Sir Edmund Hillary, and the Apollo Program." In the early 1970s, obtaining sequence information on DNA or RNA was arduous, typically requiring an entire year to deduce about fifteen nucleotides. Advances in laboratory methods triggered hope in the mid-1980s that a massive scale-up could eventually sequence the entire 3 billion base pairs of human DNA. The project was officially launched in October 1990 in the United States and soon became international, with major efforts in Britain, France, Scandinavia, and Japan. Specific goals, by chromosome, were set to achieve the mapping of genes to chromosomes, the physical map of DNA fragments, and then the DNA sequence. By 1994 there were 5,000 highly useful markers for the genetic map, and overlapping cloned fragments of DNA to create physical maps, using various techniques. Many clever schemes have been put to use to assure sufficient overlaps to orient the location and direction of DNA sequence fragments. Powerful sequencing methods accelerated the target completion date from 2005 to 2003, and then to 2001. Work to "clean-up" the sequence is ongoing.

Nevertheless, having the entire sequence has been likened to having the complete works of William Shakespeare as a sequence of the twenty-six English letters with no punctuation of any kind. Figuring out where the genes are and how they are turned on and off, or up and down, during life's events is a huge remaining task. In reality, the work of understanding the genome has only just begun. Computer algorithms, including one called "GRAIL," have been designed to find and use characteristics that may distinguish coding regions from the other 95 percent of the DNA sequence. Working backward from the mRNA molecules by forming double-stranded complementary DNA with the enzyme reverse transcriptase, and then sequencing the cDNA or even partial cDNA as expressed sequence tags, has accelerated this work.

Another powerful approach has utilized the theme of "unity in diversity" that characterizes all living things. There are amazing homologies between genes in humans and genes for similar functions in mice, earthworms, fruitflies, and even yeast cells, all of which have smaller genomes than humans. Computer databases available to scientists throughout the world permit "virtual experiments" using knowledge of a disease-related gene in the mouse, for example, to deduce what gene might account for a similar disease in humans.

Regulation of gene expression is a crucial feature of differentiated cells in complex organisms and of development from the single fertilized egg cell. Except for red blood cells, which have no nucleus, all other cells in any individual have a nucleus, chromosomes, and DNA—the same DNA. So the information content is essentially the same in all cells, yet quite different sets of genes are active in the blood, liver, kidney, brain, heart, and other organs and in cancer cells. Much is being learned about the ways in which genes are regulated in health and disease.

Interaction of Genes and Environmental Factors

For many decades there were disputes about whether inheritance or environment were more important in determining health status. The debate was framed as genetics versus environment, or nature versus nurture. That kind of thinking is no longer appropriate. It is firmly established that genes act by generating a molecular framework in cells and organisms, including people, that environmental factors act upon. Thus, people are exposed to many kinds of radiation; noise; chemicals and infectious agents in air, water, food, consumer products, cigarettes, alcohol, and drugs; as well as to physical and psychosocial stresses—all of which may interfere with normal cellular functioning. For example, chemicals called polycyclic aromatic hydrocarbons are produced in the combustion of gasoline, oil, cigarettes, and various industrial processes; these chemicals are breathed in through the lungs, enter the circulating blood, are activated in the liver and other organs into very reactive intermediates, and attack the DNA, forming chemical adducts with the DNA. These adducts cause the DNA code letters to be misread, generating mutations in the genetic information of these cells and increasing the risk that these cells will evade normal growth controls and become cancers. Behavioral follow-up studies in Scandinavia of adults who were adopted as infants have provided potent evidence that genetics and biology are crucial to future risks for alcoholism, depression, schizophrenia, and even criminal actions. There is now evidence of relevant inherited variation in dopamine receptors in depression, cigarette-smoking behaviors, and dysfunctional alcoholic intake. Such genetic variation may account for predisposition or resistance to these behavioral disorders.

Many pharmaceutical agents have variable therapeutic effects and variable adverse effects in different patients. In many cases we understand the reason: the drugs are metabolized (changed by enzyme action) into more active, or less active, molecules, depending on the inherited form of the gene coding for that particular metabolizing enzyme. Other chemicals from the external environment may undergo similar variable steps due to the same genes. Interactions of infectious agents with their "hosts," like infected people, may vary with genetic variation in the microbe and genetic variation in the infected person. Responses to high cholesterol foods or to cigarette smoking are subject to marked variation in people with different patterns of relevant genes. The study of these genetic-environmental interactions is called "ecogenetics."

Significance of Genetics in Clinical Medicine

There are well-recognized patterns of inheritance involving particular disease genes. If a disorder occurs in a grandparent, parent, and child, such vertical transmission in the pedigree is called dominant (caused by an abnormal gene from just one of the grandparents), and can involve either the X chromosome or any of the twenty-two autosomal chromosomes. Examples are Marfan's syndrome and Huntington's disease. If both parents appear normal, yet carry a recessive mutation, disease may occur when a child receives the mutant gene from each parent; examples include sickle-cell anemia and cystic fibrosis. Finally, the recessive gene may be carried on the X chromosome without manifestation in the female, but with full manifestation in the XY male, who has no normal second X gene; examples are hemophilia and Duchenne muscular dystrophy.

For common diseases like coronary heart disease, diabetes mellitus, breast cancers, depression, cleft lip and palate, and high blood pressure, multiple genes are involved; the heterogeneous causes vary within any group of diagnosed patients. Identical twins are much more likely than nonidentical (fraternal) twins to have the same disease; siblings and other close relatives have higher risks than unrelated individuals. In all cases, environmental factors, maturation factors, and other genes influence the age of onset of disease and the specific manifestations.

It is quite miraculous that such a high proportion of babies appears to be "normal"—within the broad range of normal physical and mental development. Nevertheless, about 3 percent of newborns have major malformations affecting the heart, colon, bones, or other organs. Some 2 to 5 percent have severe or moderate mental retardation or developmental disabilities. Chromosomal abnormalities account for many of the malformations, and various gene mutations contribute to the disabilities. Major chromosomal abnormalities are particularly common in spontaneously aborted fetuses (up to 50%). Variations within the normal range influence height, body habitus, propensity to weight gain, and mental development and temperament.

One of the important concepts in genetic medicine is "inborn errors of metabolism," a phrase introduced by Sir Archibald Garrod in 1908. Specific mutations, usually involving both the maternal and the paternal forms of the gene (autosomal recessive pattern of inheritance, with 25% risk for each offspring), cause deficiency of a key enzyme—as in mental retardation due to a block in the metabolism of the amino acid phenylalanine, which becomes toxic to the developing brain. The effects of this disorder (phenylketonuria, or PKU) can be prevented by diagnosing the condition at birth through newborn screening of a heel-stick blood sample and putting the child on a diet low in phenylalanine for the first five years of life, while the brain is growing rapidly. The special diet can be less stringent (but should, it now seems, be sustained) during childhood and adolescence. For women, it is crucial that they be back on a stringent low-phenylalanine diet during pregnancy; otherwise, the high circulating levels will definitely damage the fetus (100% risk of mental retardation).

Autosomal dominant diseases, like those which affect collagen in bone, cartilage, skin, and teeth, typically distort key proteins that have two or more polypeptides, such that a mutation in one makes the whole protein complex malfunction.

Knowledge from the Human Genome Project should allow identification of susceptibility genes for a broad array of diseases, thereby permitting testing before symptoms become manifest. If a single gene is responsible, testing during pregnancy or at any other appropriate time of life for the particular disease may predict a high risk or eliminate worry about that specific disease. For example, a person found to carry an inherited mutation in one of the colon cancer mutation repair genes could benefit from annual colonoscopy beginning at age thirty, so that any polyps would be detected and removed long before they progress to a potentially invasive cancer. In more complicated inherited conditions, multiple genes will be tested using new microarray and protein expression methods, answers will be couched in terms of increased or decreased risk and the likelihood of favorable responses to treatment. In other situations, the value of testing is limited due to lack of effective treatments, as for Huntington's disease. Of course, it is hoped that research will lead to effective therapies and preventive interventions and patients and families do value having the correct diagnosis, even if therapy is not (yet) available.

The Human Genome Project Elsi Program

One of the distinctive and important features of the Human Genome Project is its Ethical, Legal, and Social Implications (ELSI) program. James Watson committed a part of the annual appropriation from Congress to such matters from the start of the project. Three major categories of issues that have been examined in conferences, workshops, commissioned papers, and surveys are fairness, privacy, and safety.

Fairness. In the use of genetic information, fairness is especially important in preventing discrimination in access to affordable health care and life insurance and in employment. Many Americans fear genetic testing will identify a predisposition that will be (unfairly) considered a "preexisting condition" by insurance companies. As a result, genetic counselors advise that patients and families have good insurance in place before seeking counseling and testing. Even so, many individuals seek to be tested anonymously.

Privacy. Medical records and insurance health exams are not secure. In the state of Michigan, a 1999 report from the Governor's Commission on Genetic Privacy and Progress led to enactment of seven model statutes in 2000. Federal legislation is pending.

Safety and Efficacy of the Tests. Many new tests emerging from research labs need to be converted to high throughput, less expensive methods, with reliable quality-assurance programs. In general, people will be tested only once, and the test results carry implications for relatives. Autonomy of the individual has been the explicit policy for genetic counseling and informed participation in genetic screening for many years; testing must be conducted with similar respect for individual preferences and decisions.

Significance of Genetics in Public Health

The sequencing of the human genome and the subsequent demonstration of variation in numerous genes in health and disease will surely stimulate a golden age for the public health sciences. It will be essential to investigate and link data about microbial, chemical, and physical exposures; about nutrition, metabolism, growth, and development; about lifestyle behaviors; and about diagnoses, medications, and health care utilization to information about genetic variation. Such studies must be conducted on a population basis in order to interpret the significance of the genetic variation. Laboratory scientists, clinician-investigators, and health care professionals will rely upon epidemiologists, biostatisticians, environmental health scientists, behavioral scientists, health economists, and health-policy analysts for the collaborative research that will inform evidence-based, cost-effective medical care and public health interventions.

In research, practice, and policy, both genetics and public health focus on populations. Both are interested in clinical preventive services and in prevention of environmental and behavioral risks. Both fields explicitly recognize cultural, societal, ethnic, and racial contexts. Geneticists are particularly sensitive to the legacy of the eugenics movement of several decades ago and to the conundrum of making medical decisions when no treatment or preventive intervention is yet known. So long as the United States lacks universal health insurance, discriminatory use of genetic information by insurers and by employers must be guarded against, as noted above.

More knowledge is needed about the heterogeneity of genetic predispositions, environmental exposures, and disease risks. Unfortunately, most public health research on infectious disease and environmental chemical risks has paid little attention to inherited susceptibility in people, focusing only on the environmental-disease agents. Similarly, heterogeneity of study populations has often been neglected in epidemiologic studies in the effort to generate sufficient numbers to justify the analysis statistically. For quantitative traits, pharmacologists, toxicologists, and psychologists have generally emphasized means and standard errors of the means, and neglected potentially informative people with values outside two standard deviations from the mean. Nevertheless, genetics is now at the core of research on cancers, coronary heart disease, high blood pressure, neurological and psychiatric conditions, and a host of other common conditions.

Complete genome sequences are now available for Mycobacterium tuberculosis, HIV, and hepatitis B virus; sequences will soon be available for cholera, malaria, and other agents. The ability to promptly identify disease-causing strains of these infectious agents has been a boon to epidemiologic surveillance in the community and to clinical management of patients. Genetic variation in both the agents and exposed persons interact. For both HIV and malaria, there are cell-surface variants of blood cells in humans that protect some people from infection. These host-parasite relationships will be a fertile area for new knowledge in public health and for drug development.

Nutrition and genetics interact extensively. Individuals with similar elevated levels of cholesterol have a variety of underlying conditions for which different dietary and pharmacologic approaches are needed. Another important risk factor for coronary heart disease is the amino acid homocysteine, whose level is greatly influenced by folic acids and vitamins B12 and B6, as well as genetic variation in enzymes metabolizing these vitamins. One common disorder, hereditary hemochromatosis, results from an overload of iron from the diet, leading to damage from iron deposition in the heart, liver, pancreas (diabetes), testes (infertility), skin, and joints (arthritis). Simple blood donation can reduce iron burdens in the body and prevent these serious complications. It is easy to test for elevated iron levels and for the gene mutations that predispose to the retention of excess iron. Unfortunately, the American Red Cross refuses to accept blood from these otherwise normal potential donors, and the Centers for Disease Control has been extremely cautious about undertaking screening programs on a population basis.

In the arena of environmental health, variation in susceptibility has been recognized as one of the three key components in assessment of risks, together with the dose-response relationship and the levels of exposure in relevant settings. The U.S. government has mounted an Environmental Genome Initiative to direct emerging knowledge of genes and genetic variation from the Human Genome Project and develop powerful new methods of chip technology for testing lots of genes simultaneously as an aid in identifying and preventing health risks from environmental exposures.

Across all of these fields, genetics will surely contribute to a scientifically sound strategy for improving health, preventing disease, and reducing disparities, the overarching missions of public health.

(SEE ALSO: Autonomy; Environmental Determinants of Health; Eugenics; Genes; Genetic Disorders; Human Genome Project; Medical Genetics; Nutrition; Retrovirus; and articles on specific diseases mentioned herein)

Bibliography

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U.S. Congress, Office of Technology Assessment (1988). Mapping Our Genes: The Genome Projects: How Big, How Fast? Washington, DC: U.S. Government Printing Office.

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Watson, J. D., and Crick, F. H. C. (1953). "A Structure for Deoxyribose Nucleic Acid." Nature 171:737–738.

— GILBERT S. OMENN

Genetics is the scientific study of the structure, function, and transmission of genes in living things. The field of genetics includes many disciplines and uses many different techniques. Historically, genetic scientists (geneticists) investigated patterns of inheritance in whole organisms by observing the distribution and segregation of physical characteristics across several generations of breeding. This type of genetic research, called classical or Mendelian genetics, is still conducted today and remains invaluable for identifying and describing inheritance patterns and traits. The development of modern molecular biology and biochemistry has facilitated the growth of a different but complementary branch of genetic research, known as molecular genetics. This branch focuses on understanding the detailed molecular mechanisms that govern the transmission of genetic material from one generation to the next.

The observable characteristics that describe any organism (for example, height or eye color in humans, or flower size and color in plants) can be broadly grouped into two categories: those that are acquired because of environmental effects, and those that are inherited. Genetics is concerned with this second category—that is, inherited characteristics. Gregor Mendel, an Augustinian monk of the mid-nineteenth century, observed that characteristics such as shape and color in peas were passed from parent to offspring regardless of the environment the plants grew in. He meticulously counted and documented thousands of crosses between different pea varieties to deduce the principles that governed this inheritance. In the end, his work was so influential and vital to the development of genetics that the term "Mendelian" genetics is now a synonym for classical genetics.

Several key concepts put forward by Mendel have been expanded, as the science of genetics has grown. It is now known that genetic information is passed on as a series of discrete units known as genes, each of which is associated with specific traits. Furthermore, most organisms (including humans) get two copies of their genetic information, one from each parent. This means that most living things have two copies of each gene, and that these two copies are not necessarily the same, since they came from different parents. When an organism reproduces, it passes only one of its two copies to an offspring. Importantly, copies of different genes separate (segregate) randomly into the next generation, which means that an offspring can receive either of the two copies that the parent has, and that the set of copies that is passed is different from offspring to offspring.

A growing interest in the biochemical basis of life led geneticists of the twentieth century to attempt to identify the substance that carries genetic information from one generation to the next. Intense research led to the discovery of DNA (deoxyribonucleic acid), the molecule that encodes the genetic information of almost all organisms (a few viruses use RNA—ribonucleic acid—to encode their genes). Understanding the relationship between observable, inherited traits and the structure and organization of the genetic material (DNA) is the primary focus of molecular genetic research. The powerful combination of classical genetics and molecular genetics has led to many important advances in biological and health-care research and continues to be a major force in the advancement of science in the twenty-first century.

—Daniel J. Tomso

For more information on genetics, visit Britannica.com.

Genetics, the science of heredity, includes the interrelated fields of cytology, biochemistry, evolutionary theory, and molecular biology. Today the impact of genetic research is far-reaching, affecting medical diagnosis and therapeutics, agriculture and industry, criminal prosecution, and privacy, as well as ideas regarding individuality, ethics, and responsibility. Studied since antiquity, heredity remained a puzzle until the late twentieth century even though many of its essential physical components—such as chromosomes and "nuclein" (later identified as deoxyribonucleic acid (DNA)—were known by the late nineteenth century. Indeed, genetics did not become a "science" in a contemporary empirical sense until the rediscovery of Gregor Mendel's laws in 1900. Mendel, an Austrian monk who experimented with patterns of inheritance in studies of peas and flowers, determined laws of heredity regarding the integration and assortment of inherited traits. These original principles underwent considerable refinement and expansion throughout the twentieth century as scientists uncovered the physical and chemical mechanisms of heredity. This recent history of genetics can be divided into three general periods: classical genetics, molecular genetics, and applied or modern genetics, each of which benefited greatly from American researchers and institutions.

Classical and Molecular Genetics

The rediscovery of Mendel's laws led to the flowering of classical genetics in the early twentieth century. Population studies, breeding experiments, and radiation were among the early tools in genetic research as scientists looked to uncover the patterns and basic unit of heredity as well as the causes of variation. In 1902, a mere two years after the rediscovery of Mendel's laws, the American biologist Walter S. Sutton observed similarities between Mendel's genetic "units" and chromosomes. Additional research by his Columbia University colleague Edmund Beecher Wilson confirmed the link and identified the "X" sex chromosome in butterflies, while another American, the cytologist Nettie Stevens, independently identified the "Y" chromosome in beetles. The existence of sexlinked genetic traits, such as white eyes in fruit flies (Drosophila melanogaster), was shown by the American biologist Thomas Hunt Morgan in 1910 in studies capable of locating a specific gene on a specific chromosome. Using light-microscope observations, Morgan and his students Alfred Henry Sturtevant, Hermann Joseph Muller, and Calvin Blackman Bridges studied the phenomenon of crossing-over, the process by which chromosomes exchange genes, and as a result were able to construct chromosome maps. Their research proceeded quickly; in 1915, the "Drosophila" group at Columbia University published The Mechanism of Mendelian Heredity—a seminal work that demonstrated the linear arrangement of genes in the chromosome and helped explain abnormal genetic ratios and variation. However, explanations for genetic variation remained unsatisfactory until the pioneering work of Hermann Muller at the University of Texas. Muller experimented with radiation and high temperatures to measure rates of mutation, eventually determining that genes, while generally stable, can be externally induced to mutate. (This discovery also opened the possibility of genetic engineering.) His Artificial Transmutation of the Gene, published in 1927, also hinted at the gene's ability to control metabolism and morphology, leading biochemists and other scientists to investigate the physical composition of the gene and the chemical basis of heredity.

Beginning in the 1940s, techniques such as bacterial vectors and X-ray diffraction analysis led to the development of both biochemical genetics and molecular genetics. In 1941, the Stanford biologist George Wells Beadle and biochemist Edward Lawrie Tatum proposed the one gene–one enzyme theory after experimenting on the nutritional requirements of mutated bread mold, ushering in the field of biochemical genetics by providing an introductory blueprint for the chemical synthesis of enzymes. A few years later, in 1944, the American geneticists Oswald Avery, Colin MacLeod, and Maclyn McCarty transformed bacteria through the introduction of foreign DNA, thereby determining that DNA was the primary heredity material. This indicated that DNA, rather than the previously suspected class of proteins, was the actual carrier of genetic information. Further proof came in 1952 when the American geneticists Alfred D. Hershey and Martha Chase, working at the Cold Spring Harbor Biological Station in New York, demonstrated that viral DNA was responsible for replication within infected bacteria. Using a bacteriophage (a bacterial virus) as a vector, the scientists showed that it was the virus's DNA, not a protein, that infected the host bacteria. However, while DNA was clearly the molecule of heredity, questions on the structure and mechanisms of DNA remained that could only be solved by molecular biology.

By 1950, geneticists had adopted the method of X-ray diffraction analysis pioneered by the American chemist Linus Pauling at the California Institute of Technology to determine the three-dimensional structure of the DNA molecule. Pauling proposed both single-and triple-helix models, but in 1953 the American biochemist James Watson and British biophysicist Francis Crick correctly determined that the DNA molecule was a double helix. The two men proposed that DNA was transcribed into RNA, then translated or expressed as a protein, a method of genetic replication later proven by the American molecular biologists Matthew Stanley Meselson and Franklin William Stahl and now known as the "central dogma" of molecular genetics. In 1961, Crick and Sidney Brenner determined that codons, groups of three nucleotides (adenine, cytosine, guanine, uracil and thymine), were responsible for the synthesis of proteins, while the National Institutes of Health researchers Marshall W. Nirenberg and Johann H. Matthaei showed in 1965 that certain codon combinations also lead to the production of amino acids. A final piece of the genetic puzzle—the means by which genes are activated or deactivated—was resolved by the operon model of genetic regulation. Proposed by the Frenchman Jacques Monod, the operon model requires that regulatory nucleotides, which account for a substantial portion of the DNA molecule, repress the function of other genes by disrupting RNA transcription under certain conditions.

Modern Applied Genetics

The study and sophistication of genetics increased rapidly in the last quarter of the twentieth century, as scientists, aided by advances in technology and industry and government funding, concentrated on both pure and applied genetics. Recombinant DNA engineering and prenatal genetic screening for some inherited diseases became possible in the early 1970s, leading to public concern over potential misuse and eventual governmental regulation. At the same time, the central dogma expanded to include the phenomenon of reverse transcription after American virologist David Baltimore demonstrated that retroviruses were capable of reproducing themselves by copying their own RNA. Perhaps the greatest advancement in pure genetic research came in the form of the Human Genome Project. Launched in 1988 by the U. S. Department of Energy and the National Institutes of Health, the Human Genome Project succeeded in sequencing a human genome in 2000 and represents the new state of "big" biology—an international partnership of government, academic, and industrial research institutions. Although researchers expect that the project will deliver remarkable medical and biological applications, some outside observers worry about the potential for genetic discrimination, genetic racial typing (see Racial Science), and the revitalization of Eugenics, demonstrating both the promise and the danger of contemporary genetics.

Today genetics permeates both the biological sciences and American culture, surfacing in research laboratories, congressional hearings, and courtrooms as well as popular movies and books. Genetics has unified the biological sciences and led to the modern synthesis of evolutionary theory and biology by demonstrating that organisms share the same basic genetic materials and processes. DNA fingerprinting plays a vital role in criminal investigations and the establishment of paternity, while genetic screening and therapy provide hope for those suffering from inherited diseases like sickle-cell anemia, cystic fibrosis, or Huntington's disease. Entering the twenty-first century, transgenic crops may provide the best window into the future impact of genetics, as the rise of a transgenic agricultural industry, which produces crops with an increased pesticide resistance and shelf life, has also led to a counter industry based on organic, or non-genetically enhanced, crops.

Bibliography

Caulfield, Timothy A., and Bryn Williams-Jones, eds. The Commercialization of Genetic Research: Ethical, Legal, and Policy Issues. New York: Kluwer, 1999.

Kohler, Robert E. Lords of the Fly. Chicago: University of Chicago Press, 1994.

Olby, Robert. The Path to the Double Helix. Seattle: University of Washington Press, 1974. Reprint, New York: Dover, 1994.

Ridley, Matt. Genome: The Autobiography of a Species in 23 Chapters. New York: Harper Collins, 1999.

Sarkar, Sahotra. Genetics and Reductionism. Cambridge, U. K., and New York: Cambridge University Press, 1998.

Sturtevant, A. H. A History of Genetics. New York: Cold Spring Harbor Laboratory Press, 2001.

—J. G. Whitesides

Since the first efforts were made to cultivate plants, humans have employed genetics to breed crops with improved taste, hardiness, or yield. The long history of genetics and nutrition can be felt even today, and permeates many aspects of our daily life. Home gardeners can purchase seeds that will grow in particular soils, produce fruit at various times of the year, or grow in sunshine or shade. Local supermarkets sell supersweet varieties of corn and fruits such as the tangelo, made from crossing grapefruits with tangerines. The "Green Revolution," which began with the identification of a high-yield strain of wheat, has resulted in dramatic increases in food production around the world. With the advent of genetic engineering, new, disease resistant crops have been developed, with the promise of reducing requirements for pesticide use.

Plants are not the only organism to be subjected to genetic breeding programs by humans. Yeast strains for baking bread or producing alcoholic beverages have been cultured for centuries. Meatier turkeys and cows that give more milk are the product of animal breeding efforts. Some have argued that the genetic manipulation of foodstuffs has gone too far, emphasizing crops that can withstand long storage times, transportation to markets, and handling by the consumer over any selection for flavor. Others worry that genetic engineering gives us unprecedented, and perhaps dangerous, opportunities to mix and match desired traits. It is nevertheless apparent that genetics has had an enormous impact upon society.

What is genetics? Simply put, genetics is the study of hereditary variation. This variation, in essence, is the diversity of life as it exists in all its forms on earth. For example, there are perhaps some 300,000 different species of flowering plants. What makes each of these plants different from one another? Perhaps even more amazing than this variation between species, there are astounding levels of variation that can be found even within a species. There are, for example, some 6,000 different varieties of apples alone. Genetics aims to understand how this variation occurs between species as well as within species. The term "phenotype" is used to describe any differences that can be observed or measured. For example, the possession of yellow kernels is a phenotype of a particular strain of corn, which distinguishes it from strains that possess white kernels. The two may have phenotypes in common (e.g., they both have white flowers or are supersweet) in addition to the differing phenotype of yellow and white kernels. Genetics examines the ground rules regarding how these phenotypes are passed on, or inherited, from one generation to the next.

Gregor Mendel, the Father of Genetics

While genetic breeding has been practiced for many hundreds of years, the true science of genetics began with Gregor Mendel, an Austrian monk who published his seminal work in the mid-1800s. At the time, genes had not been identified; indeed, the term itself would not be coined until 1909. How traits could be inherited from one generation to another was entirely unclear. Charles Darwin himself proposed the pangenesis theory, in which traits from the parents are passed to their children in a process that "blends" them together. In this theory, children represent a melding of the two parental sets of traits. They in turn would pass their traits on to their children, further blending together the traits of their respective parents. This model of how genetics operates can be contrasted with the particulate theory, in which traits are retained on small particles passed from one generation to the next. While Darwin's model would seem to be consistent with what we can observe in our own children, Mendel's carefully performed and insightful experiments clearly supported the particulate theory, and laid down the basic principles of the inheritance of phenotypes.

Mendel discovered his principles working with pea plants, which were raised not only for their experimental value but also as a food source for the monastery. Mendel's seminal idea was to identify clearly defined and distinct traits among these plants, and determine how these phenotypes were passed from one generation to the next. For example, Mendel identified plants that possessed either white flowers or purple flowers, but not both. He then crossed these two different variants with one another (the "parental," or P0 generation), and examined the flower color of the resulting progeny plants in the filial, or F1, generation. If the blending theory were correct, one might expect pink flowers to be produced in the F1 plants. Instead, Mendel obtained only purple flowered plants. If these F1 purple-flowered plants were then interbred with one another, producing an F2 generation of plants, Mendel saw once again pea plants with white flowers. Thus, even though this particular trait (white flowers) had not been seen at all in the F1 generation, it had been retained, and could be recovered in the F2 generation. These results clearly supported the particulate theory.

To obtain his results, Mendel studied the transmission of seven distinct phenotypes among some 28,000 pea plants, and synthesized them into a mathematical model of genetic inheritance. In doing so, he did what had never been done before; he quantified his results. From an analysis of his data, he was able to infer several key principles. He argued that there must exist determinants that specify particular phenotypes, a feature we now recognize as genes. He also argued that these determinants are located on particles, one of which is donated by the father, and one by the mother. These particles, now known to be chromosomes, produce a progeny plant that has one determinant for flower color donated by the mother, and one determinant for flower color donated by the father. The phenotype of the progeny plant will depend upon the particular combination of determinants it receives from its parents. Mendel deduced that the determinant for the production of purple flowers (represented as "P") is dominant over the determinant to produce white flowers (represented as "p"). Conversely, the white flower determinant is recessive in the presence of the purple-flower determinant. Two copies of the purple-determinant (P/P) in a plant, one maternal and one paternal, results in purple flowers. One purple and one white flower determinant (P/p) still produces purple flowers. Only if a plant receives two white flower determinants (p/p) will it possess white flowers.

Mendel's results were not widely known at the time. Some thirty-five years later, his work was "rediscovered" by geneticists who had repeated his results in other organisms. The implications of Mendel's work were revolutionary. For the first time, it was possible to observe the patterns of inherited phenotypes of a plant, animal, insect, or bacterium, and deduce, with mathematical precision, the expected genotypes of these organisms. It is a tribute to the work of Mendel and others of his time that their results were obtained despite not knowing that genes were encoded by DNA or how genes act to produce the observed phenotype.

Single Gene Effects

Part of Mendel's success was due to his implicit recognition that there are two primary types of variation: discontinous and continuous. In discontinuous variation, a particular phenotype can be found in a population in at least two distinct forms. For example, Mendel's peas possessed purple or white flowers, and not both. On the other hand, in continuous variation, a range of similar phenotypes can be observed in the population. An example of this among humans might be the observation that noses come in all shapes and sizes. In most instances, genetics has focused predominantly upon discontinuous variants, as the associated phenotypes can be clearly recognized and categorized. As it turns out, many of the phenotypes that fall into this group can be associated with alterations in the function of a single gene. In our purple versus white flower example, the gene that is normally responsible for giving the plant its purple color has been mutated, such that it no longer functions. In the absence of this gene, white, or uncolored, flowers are produced. The different forms of this same gene (P, indicating normal or wild-type function, and p, indicating altered or mutant function) are called alleles. If an allele is widely represented in the population, as is the case among white or purple flowers in pea plants, they are termed polymorphisms.

Polymorphisms can be identified in other organisms as well. However, in humans, there are also additional issues of ethnicity and race. A common polymorphism among Asians, for example, is a particular allele of the alcohol dehydrogenase 2 (Adh2) gene. This allele negatively affects the enzyme's ability to metabolize alcohol, and is possessed by more than 90 percent of the Japanese population. In the European population, on the other hand, less than 10 percent have this allele. Similarly, lactose intolerance is due to allelic variation in the lactase gene. An allele that leads to low activity of lactase following early childhood is common in Africans and Asians (>80 percent), and rarer in Caucasians (17–50 percent). These relatively common polymorphisms are just a few of the many thousands of alleles known to exist in humans.

Why these polymorphisms exist is not clear, although it can be hypothesized that they either do no harm to individuals who harbor these particular alleles, or, if they are in fact somewhat harmful, are nonetheless still of some benefit. This can be described as the fitness of the allele. For example, as many as 10–20 percent of the European population bears a polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR). These individuals have a greater risk of neural tube defects, such as spina bifida, due to the fact that this allele affects folate metabolism. Why then, is such a polymorphism maintained in such a high percentage of the population? The answer may lie in the observation that individuals with this polymorphism have an increased efficiency of blood clotting. As mortality resulting from bleeding after childbirth was a common occurrence, this would be beneficial to individuals bearing this polymorphism. While it is often dangerous to speculate why a polymorphism exists, if this reduction in risk is substantiated, it would obviously be of benefit both to the individual and the population as a whole.

While we have centered this discussion around polymorphisms, on occasion, an allele will arise that affects only a small percentage of the population. Although these rare variants are uncommon (<1 percent of the population), they make up a large proportion of the patients that are hospitalized for medically related conditions. One such example would be phenylketonuria, which occurs in one out of every 10,000 births. This medical condition is due to a mutation in the phenylalanine hydroxylase gene, and leads to a failure to metabolize phenylalanine containing compounds, such as aspartame. If unrecognized, infants with PKU invariably develop mental retardation. This can be avoided by monitoring dietary intake to eliminate phenylalanine-containing compounds. How is PKU inherited from one generation to another? The fields of medical genetics and genetic counseling encompass the analysis of family histories, so as to better treat individuals who are at risk from these illnesses. If we examine the family history of a typical patient that has PKU, we might observe the following:

In this case, neither parent in the P0 generation suffers from the disease, but some of their children do. Applying principles learned from Mendel's work, we can infer the genotype of the family members from this phenotypic analysis:

From the study of this family history, it is clear that PKU is inherited in a recessive manner. Adults who are heterozygous for mutations in the phenylalanine hydroxylase gene (K/k; possessing one wild-type or normal allele and one mutant allele) do not have PKU. Only those with two mutant copies (k/k) display the condition. Thus, Mendel's laws apply equally well to humans as they do to peas. Interestingly, however, while the phenotype of PKU patients indicates a recessive inheritance of this condition, an analysis of the genotype of these patients and the population in general reveals the existence of more than 400 alleles of the phenylalanine hydroxylase gene. This astounding degree of allelic heterogeneity indicates that most PKU patients indeed possess two mutant alleles of the hydroxylase gene, but that these two alleles are likely to be completely different. The phenotypic effect is the same; elimination or severe alteration of the normal function of the gene leads to PKU. The molecular basis of this defect, however, is dependent upon the specific alleles that are involved. It is plain to see that the field of molecular genetics, which examines the actual genes responsible for these defects, is an important complement to more traditional genetic phenotypic observations.

While the examples we have looked at so far have comprised diseases or phenotypic traits that are inherited in a recessive fashion, many diseases are inherited in a dominant manner. In these instances, a single copy of the mutant allele is sufficient to confer, at least partially, a medically associated condition. An example of this might be familial hypercholesterolemia, which is associated with an inability to properly metabolize cholesterol. A family history of patients with this affliction might appear thus:

Compare the rate of occurrence of this condition with that of PKU. Only a single copy of the mutant allele is required to produce at least some phenotype in cases of familial cholesterolemia. In many of these dominantly inherited diseases, individuals that possess two mutant alleles are much more strongly affected than individuals with one mutant and one wild-type allele. In familial hypercholesterolemia, homozygous patients (those with two mutant alleles; H/H) rarely live past the age of 30. These individuals are rare, however, occurring in perhaps one in one million. Heterozygous individuals (those with one mutant and one wild-type allele; H/h), on the other hand, are extremely common, and are present in perhaps one in 500. These individuals have a higher propensity for premature heart disease due to the buildup of atherosclerotic plaques, but without the severity of phenotype exhibited by homozygous individuals.

These examples illustrate just a few of the more than 1400 single-gene disorders that have been identified. It has been estimated that in any one individual, perhaps 20 percent of all genetic loci are heterozygous. This suggests that a striking degree of individuality exists at the genetic level. This allelic variation may explain, for example, the differential response of individuals to environmental, dietary, or pharmacological effects.

Multiple Gene Interactions

So far, we have discussed examples of phenotypes that can be traced to alterations of a single gene. While great strides have been made in identifying genes that are associated with a particular phenotype, it is clear that we are far from understanding how genes interact with one another as a whole. For example, many genetic disorders are thought to result from the interplay of multiple genes with epigenetic, or environmental, influences, such as diet. One means of trying to understand these multifactorial disorders and how genes and the environment interact is to examine at a molecular level how genes function. While Mendel derived his results from observing the phenotype of his plants, a molecular geneticist might ask, what is the actual gene that is responsible for production of purple pigment? What is its sequence? How does it function in the plant cell to produce color? With what other genes does it interact?

DNA has often been called the "blueprint of life," and indeed, DNA is the thread that ties almost all life on earth together. Rules that govern the replication of DNA and its transmission to daughter cells (e.g., during cell division) are the same in nearly all organisms. But if DNA is DNA whether or not it is found within a fly or a human, how is it possible to obtain such diverse organisms? The answer, of course, is that the genes that exist within DNA are different from flies to humans. One might suspect that these two diverse organisms would possess radically different sets of genes, separated as they are by over 600 million years of evolution. With the advent of the Human Genome Project, it has become possible to directly test this hypothesis. Once the entire sequence of human DNA was known, it was compared to the sequence of Drosophila melanogaster, a fruitfly that has been used for over one hundred years as a genetic model. This comparison revealed an astonishing 40 percent of all genes in the human have similar counterparts in the fruit fly. While this figure is still tentative, and gene number is hardly an adequate means of comparing differences among species, it underscores yet again that genetic principles learned in model organisms, such as the fruit fly, can have important theoretical and practical applications in understanding human genetics.

If variation between species is accomplished, at least in part, by genes that are unique to flies or humans, how does variation occur within a species? All cells in the human body, with the exception of those involved in the production of sperm or ovum, contain identical DNA sequences, and therefore identical sets of genes. How is it then, that a skin cell will develop differently from a hair cell, if both contain the same DNA? The answer is that each cell may contain the same genes, but not all the genes will be expressed in each cell. Current estimates suggest that there are approximately 50,000 genes in the human genome. Any given cell type, however, is thought to express some 15,000 of these genes. Thus, a hair cell will express 15,000 genes, but these genes will be somewhat different from the 15,000 that are expressed by a skin cell. It is this differential gene expression that leads to the differences in observed phenotype between the two cell types. In a similar vein, two noses located on the faces of two different individuals may well be specified by the same 15,000 genes, but slight differences in their expression from one individual to the next may well explain the somewhat petite nose on one and the rather large proboscis on the other. The growing field of genomics aims to study, at a global level, the interactions of all of the genes that contribute toward a particular phenotype.

If it does indeed require 15,000 genes to produce any given cell in the body, then mutant alleles that arise in any one of these genes may, or may not, strongly affect the development of that cell. Alleles of certain genes may alter the color of the cell, or perhaps its ability to metabolize phenylalanine-containing products. Or it is possible that an alteration in just one gene among 15,000 may have no discernable effect at all. How these thousands of genes interact with one another to produce a given trait is perhaps the biggest challenge that faces the molecular geneticist studying genomics today. Moreover, these genetic interactions are often complicated by epigenetic influences as well. Nutrition, in particular, has very strong effects on gene expression. Many multifactorial diseases, such as diabetes, are thought to be associated with both genetic and environmental risk factors. A given family history may, to the medical geneticist, indicate a predisposition towards diabetes, but other factors, such as diet and exercise, are also thought to influence the development of this disease.

One particularly fascinating example of the link between nutrition and genetics is the effect of diet upon aging. Unusual longevity in humans has often been attributed by these self-same individuals as directly associated with the manner in which they have lived their life. Whether it is a glass of wine each day, eliminating red meat, or ingesting large quantities of vitamin C, these individuals claim to have identified the reason behind their advanced years. How much can truly be attributed to these epigenetic influences, and how much is based upon the individual's particular genetic makeup? Research in model organisms such as the fruit fly has identified a handful of genes that seem to strongly affect the lifespan of the fly. Mutations in the methuselah gene, for example, allows flies to survive more than 35 percent longer than their normal lifespan. This astonishing result suggests that aging may actually be strongly influenced by a limited number of genes, many of which are involved in metabolism. On the other hand, it has long been known that reducing the calorie intake of rodents by 40 percent can also markedly increase their lifespan. The new field of genomics has begun trying to identify the molecular basis for this increase in longevity, by comparing how many genes are differentially expressed between calorie-restricted rodents and their non-restricted counterparts. It was found that hundreds of genes had been affected, including a large number known to be involved in metabolic processes. Thus, the effects of nutrition on aging can be profound. How much of this is due to our genes? How much can attributed to single genes? How much is due to our caloric intake? The answer to this "age-old" question remains to be determined.

A similarly tantalizing example demonstrating the link between nutrition and genetics lies in the area of control of bodyweight. Mice that are homozygous mutant for a particular allele of the obese gene (ob/ob) are grossly overweight. The excitement that surrounded this result centered around the possibility that weight gain might be strongly influenced by individual genes, and that no amount of dietary control or exercise can alleviate its effects. This, of course, has been shown to be a gross oversimplification, and it is clear that many genes are involved in the regulation of body weight. Nevertheless, it is apparent that the field of genetics is gradually beginning to unravel some of the major problems in nutrition and biology today.

Conclusions

The practice of genetics is as old as the human race, and yet as a science, it is still in its infancy. The study of genetics stretches across all of biology, and has grown to include many sub-specialties within the field. Cytogenetics, for example, is the study of chromosomal defects, such as trisomy 21. Molecular genetics is the analysis of individual genes, such as Adh2, and their function within the cell. Population genetics studies the frequency with which polymorphisms of Adh2 occur within large subsets of individual organisms. Medical genetics searches to identify patterns of inheritance of diseases within patients, and the effect of epigenetic influences such as diet and exercise. And finally, genomics tries to understand how genes behave as a whole to specify particular cell types or phenotypes. Together, these diverse but inter-related fields aim to understand how variation is established and maintained within biology.

Bibliography

Brown, P. O., D. Botstein. "Exploring the New World of the Genome with DNA Microarrays." Nature Genetics 21 (1 Suppl) (1999): 33–37.

Griffiths, Anthony J. F., J. H. Miller, David T. Suzuki, Richard C.Lewontin, and William M. Gelbart. An Introduction to Genetic Analysis. 7th ed. New York: Freeman, 2000.

Jorde, Lynn B., John C. Carey, Michael J. Bamshad, and Raymond L. White. Medical Genetics. 2d. ed. St. Louis: Mosby, 1999.

Lee, C. K., Weindruch Klopp, T. A. Prolla. "Gene Expression Profile of Aging and its Retardation by Caloric Restriction." Science 285 (1999): 1390–1393.

—David Ming Lin

The study of heredity, or how the characteristics of living things are transmitted from one generation to the next. Every living thing contains the genetic material that makes up DNA molecules. This material is passed on when organisms reproduce. The basic unit of heredity is the gene. (See chromosomes; dominant trait; genetic code; Gregor Mendel; recessive trait; and sexual reproduction.)

The branch of biology dealing with the phenomena of heredity and the laws governing it. Expressed in other definitions, e.g. population genetics.

• biochemical g. — the science concerned with the chemical and physical nature of genes and the mechanism by which they control the development and maintenance of the organism.
— The field of biochemical or molecular genetics is relatively new and is increasingly used to define the cause of many inherited diseases. These diseases usually result from defective protein synthesis, such as hemophilia A and immunodeficiency, and more than 200 so-called ‘inborn errors’ of metabolism identified thus far in animals, such as mannosidosis and galactosemia, in which lack or alteration of a specific enzyme prohibits proper metabolism of carbohydrates, proteins or fats and thus produces clinical signs.
• clinical g. — the study of the possible genetic factors influencing the occurrence of a pathological condition. In addition to the diseases mentioned under biochemical genetics, other aspects of clinical genetics include the study of chromosomal aberrations, such as those that cause testicular hypoplasia, and immunogenetics, or the genetic aspects of the immune response and the transmission of genetic factors from generation to generation.
• molecular g. — the study of the molecular structure of genes, involving DNA and RNA. See also deoxyribonucleic acid.

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

For a generally accessible and less technical introduction to the topic, 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 a person's height, the nutrition and health that person experiences in childhood also have a large effect.

Contents 1 History 1.1 Mendelian and classical genetics 1.2 Molecular genetics 2 Features of inheritance 2.1 Discrete inheritance and Mendel's laws 2.2 Notation and diagrams 2.3 Interactions of multiple genes 3 Molecular basis for inheritance 3.1 DNA and chromosomes 3.2 Reproduction 3.3 Recombination and linkage 4 Gene expression 4.1 Genetic code 4.2 Nature versus nurture 4.3 Gene regulation 5 Genetic change 5.1 Mutations 5.2 Natural selection and evolution 6 Research and technology 6.1 Model organisms and genetics 6.2 Medical genetics research 6.3 Research techniques 6.4 DNA sequencing and genomics 7 Notes 8 References 9 External links

History

Main article: History of genetics

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.

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]

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]

Molecular genetics

James D. Watson (pictured) and Francis Crick determined the structure of DNA in 1953.

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]

Features of inheritance

Discrete inheritance and Mendel's laws

Main article: Mendelian inheritance

A Punnett square depicting a cross between two pea plants heterozygous for purple (B) and white (b) blossoms

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.

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.

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.

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: color or 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 (eg. purple or white flowers) but are instead continuous features (eg. 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]

Molecular basis for inheritance

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 has 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.

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.

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]

Gene expression

Genetic code

Main article: Genetic code

The genetic code: DNA, through a messenger RNA intermediate, codes for protein with a triplet code.

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]

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

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.

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 (eg. ribosomal RNA and transfer RNA). RNA can also have regulatory effect through hybridization interactions with other RNA molecules (eg. microRNA).

Nature versus nurture

Siamese cats have a temperature-sensitive mutation in pigment production.

Although genes contain all the information an organism uses to function, the environment plays an important role in determining the ultimate phenotype—a dichotomy 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.

Gene regulation

Main article: Regulation of gene expression

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.^[51] 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.^[52]

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.^[53] 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.^[54]

Genetic change

Mutations

Main article: Mutation

Gene duplication allows diversification by providing redundancy: one gene can mutate and lose its original function without harming the organism.

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.^[55][56] (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.^[57] 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.^[58] 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).

Natural selection and evolution

Main article: Evolution

Mutations produce organisms with different genotypes, and those differences can result in different phenotypes. Many mutations have little effect on an organism's phenotype, health, and reproductive fitness. Mutations that do have an effect are often deleterious, but occasionally mutations are beneficial. Studies in the fly Drosophila melanogaster suggest that if a mutation changes a protein produced by a gene, this will probably be harmful, with about 70 percent of these mutations having damaging effects, and the remainder being either neutral or weakly beneficial.^[59]

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

Population genetics research studies the distributions of these genetic differences within populations and how the distributions change over time.^[60] Changes in the frequency of an allele in a population can be influenced by natural selection, where a given allele's higher rate of survival and reproduction causes it to become more frequent in the population over time.^[61] Genetic drift can also occur, where chance events lead to random changes in allele frequency.^[62]

Over many generations, the genomes of organisms can change, resulting in the phenomenon of evolution. Mutations and the selection for beneficial mutations can cause a species to evolve into forms that better survive their environment, a process called adaptation.^[63] New species are formed through the process of speciation, a process often caused by geographical separations that allow different populations to genetically diverge.^[64] The application of genetic principles to the study of population biology and evolution is referred to as the modern synthesis.

As sequences diverge and change during the process of evolution, these differences between sequences can be used as a molecular clock to calculate the evolutionary distance between them.^[65] Genetic comparisons are generally considered the most accurate method of characterizing the relatedness between species, an improvement over the sometimes deceptive comparison of phenotypic characteristics. The evolutionary distances between species can be combined to form evolutionary trees - these trees represent the common descent and divergence of species over time, although they cannot represent the transfer of genetic material between unrelated species (known as horizontal gene transfer and most common in bacteria).

Research and technology

Model organisms and genetics

The common fruit fly (Drosophila melanogaster) is a popular model organism in genetics research.

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.^[66] 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).

Medical genetics research

Medical genetics seeks to understand how genetic variation relates to human health and disease.^[67] 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.^[68] 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.^[69]

Although it is not an inherited disease, cancer is also considered a genetic disease.^[70] 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.

Research techniques

Gel electrophoresis is a common technique for visualizing DNA. DNA fragments are separated according to their length.

DNA can be manipulated in the laboratory. Restriction enzymes are a commonly used enzyme that cuts DNA at specific sequences, producing predictable fragments of DNA.^[71] DNA fragments can be visualized through use of gel electrophoresis, which separates fragments according to their length.

The use of ligation enzymes allows DNA fragments to be reconnected, and by ligating fragments of DNA together from different sources, researchers can create recombinant DNA. Often associated with genetically modified organisms, recombinant DNA is commonly used in the context of plasmids - short circular DNA fragments with a few genes on them. By inserting plasmids into bacteria and growing those bacteria on plates of agar (to isolate clones of bacteria cells), researchers can clonally amplify the inserted fragment of DNA (a process known as molecular cloning). (Cloning can also refer to the creation of clonal organisms, through various techniques.)

E coli colonies on a plate of agar, an example of cellular cloning and often used in molecular cloning.

DNA can also be amplified using a procedure called the polymerase chain reaction (PCR).^[72] By using specific short sequences of DNA, PCR can isolate and exponentially amplify a targeted region of DNA. Because it can amplify from extremely small amounts of DNA, PCR is also often used to detect the presence of specific DNA sequences.

DNA sequencing and genomics

One of the most fundamental technologies developed to study genetics, DNA sequencing allows researchers to determine the sequence of nucleotides in DNA fragments. Developed in 1977 by Frederick Sanger and coworkers, chain-termination sequencing is now routinely used to sequence DNA fragments.^[73] With this technology, researchers have been able to study the molecular sequences associated with many human diseases.

As sequencing has become less expensive, researchers have sequenced the genomes of many organisms, using computational tools to stitch together the sequences of many different fragments (a process called genome assembly).^[74] These technologies were used to sequence the human genome, leading to the completion of the Human Genome Project in 2003.^[23] New high-throughput sequencing technologies are dramatically lowering the cost of DNA sequencing, with many researchers hoping to bring the cost of resequencing a human genome down to a thousand dollars.^[75]

The large amount of sequence data available has created the field of genomics, research that uses computational tools to search for and analyze patterns in the full genomes of organisms. Genomics can also be considered a subfield of bioinformatics, which uses computational approaches to analyze large sets of biological data.

Notes

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References

• Alberts B, Johnson A, Lewis J, Raff M, Roberts K, and Walter P (2002). Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 0-8153-3218-1. 
• Griffiths AJF, Miller JH, Suzuki DT, Lewontin RC, and Gelbart WM (2000). An Introduction to Genetic Analysis. New York: W.H. Freeman and Company. ISBN 0-7167-3520-2. 
• Hartl D, Jones E (2005). Genetics: Analysis of Genes and Genomes (6th ed.). Jones & Bartlett. ISBN 0-7637-1511-5. 
• Lodish H, Berk A, Zipursky LS, Matsudaira P, Baltimore D, and Darnell J (2000). Molecular Cell Biology (4th ed.). New York: Scientific American Books. ISBN 0-7167-3136-3. 

External links

Wikibooks has a book on the topic of Genetics

Wikimedia Commons has media related to: Genetics

At Wikiversity you can learn more and teach others about Genetics at: The Department of Genetics

• Genetics at the Open Directory Project

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Dansk (Danish)
n. - genetik, arvelighedslære, arvelighedsforskning

Nederlands (Dutch)
genetica, genetische opbouw

Français (French)
n. - génétique

Deutsch (German)
n. - Genetik, Erbbiologie

Ελληνική (Greek)
n. pl. - γενετική (μηχανική)

Italiano (Italian)
genetica

Português (Portuguese)
n. pl. - genética (f) (Biol.)

Русский (Russian)
генетика

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n. - genética

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n. pl. - ärftlighetsforskning

中文（简体）(Chinese (Simplified))
遗传学

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n. pl. - 遺傳學
n. - 遺傳學

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n. pl. - 유전학
n. - 유전적 특질

日本語 (Japanese)
n. - 遺伝学

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‏(الجمع) علم الوراثه‏

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n. - ‮מדע התורשה, גנטיקה‬

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