The Function of Genes (Magill’s Medical Guide, Sixth Edition)
An individual is not a random assortment of characteristics. The way individuals look, their physiological makeup, their susceptibility to disease, and even how long they may live are determined by information received from their parents. The smallest unit of information for inherited characteristics is the gene. For each characteristic, an individual has two copies of the gene controlling that characteristic. The gene can have two forms, called alleles. For example, the alleles for eye color can be designated using the letters B and b, with the B allele carrying the information for brown eyes and the b allele specifying blue eyes. Thus the genotype, or genetic makeup, of an individual can be one of three types: BB, bb, or Bb. A BB individual will have brown eyes. A bb person will have blue eyes. A Bb individual will have brown eyes since the brown allele is dominant over the blue one. The dominant allele will always be expressed, whether present as two copies or only one. For a recessive allele to be expressed, an individual must have two recessive alleles (bb).
When a person reproduces, he or she passes on one allele for each gene to the child. Therefore, the child also has two alleles for each gene, one from each parent. A person with two identical alleles for a given gene is said to be homozygous for that trait and can pass on only one kind of allele. Someone with two different alleles for a particular gene is said...
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How Mutations Occur (Magill’s Medical Guide, Sixth Edition)
There is a variety of genetic information in the human population, leading to a diversity of internal and external features. The process of sexual reproduction randomly selects among that variety for each new individual who is born. Mutation is the process that created the variety originally, and it can continue to add to it today.
A human being begins as a single fertilized cell. That cell contains two copies of the genetic information in its twenty-three pairs of chromosomes. The cell divides constantly during growth and development to produce the millions of cells that make up an adult. Each one of those cells, with very few exceptions, also has twenty-three pairs of chromosomes. In order for each cell to have its own double copy of information, the DNA that makes up the chromosomes must replicate, once for each cell division. This process of replication must ensure that the information contained in the DNA is copied exactly, and for the most part, it is.
To understand how a mistake can occur, one must look at the structure of DNA, the genetic blueprint. The DNA molecule resembles a spiral staircase. The outside rails are strings of sugar molecules hooked together by phosphate groups. The steps are made of bases that project from each sugar-phosphate backbone toward the middle. The information is contained in the sequence of base pairs that make up the steps of the staircase. The bases that can form such a pair...
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Perspective and Prospects (Magill’s Medical Guide, Sixth Edition)
The modern study of genetics is conducted mostly at the molecular level. One project has identified every human gene and its location on a specific chromosome. Dubbed the Human Genome Project, it was a cooperative venture among scientists worldwide. This map tells researchers where each gene is located, and it is hoped that the defective copies in people with genetic diseases can be repaired using this knowledge. Genetic engineering techniques have already isolated many genes. For example, the gene for the production of insulin has been identified and extracted from human cells in culture. The gene has been inserted into the chromosomes of bacteria, and the bacteria are then grown in large quantities in commercial cultures. The insulin that they produce is harvested, purified, and made available to diabetics. This genuine human insulin is more potent than the insulin extracted from animals. In addition, such a process is essential for diabetics who suffer adverse reactions to the inevitable impurities that are found in insulin extracted from animals.
Ultimately, it should be possible to insert a functioning gene, like the one for insulin, directly into an afflicted person’s chromosomes—thus curing the genetic disease. The cured individual, however, would still be able to pass the defective allele on to his or her children. The possibility of splicing genes into the chromosomes of sex cells does not seem likely...
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For Further Information: (Magill’s Medical Guide, Sixth Edition)
Campbell, Neil A., et al. Biology: Concepts and Connections. 6th ed. San Francisco: Pearson/Benjamin Cummings, 2008. Chapters cover classical and molecular genetics, respectively. The text is accessible, and the many diagrams are useful.
Lewin, Benjamin. Genes IX. 9th rev. ed. Sudbury, Mass.: Jones and Bartlett, 2008. A college textbook that discusses the entire field of molecular biology and genetics, with many references to the structure and activity of the cell nucleus. Although written at the college level, it is readable and accessible to a general audience. Many highly informative illustrations and diagrams are included.
Lewis, Ricki. Human Genetics: Concepts and Applications. 9th ed. Dubuque, Iowa: McGraw-Hill, 2009. A very accessible undergraduate text that covers the fundamentals, transmission genetics, DNA and chromosomes, and the latest genetic technology, among other topics.
Radman, Mirislav, and Robert Wagner. “The High Fidelity of DNA Duplication.” Scientific American 259 (August, 1988): 40-46. Provides a readable account of the “proofreading” and error-correcting mechanisms that make mutations so rare. The author is careful to point out what is fact and what is speculation. The bibliography refers the reader to more technical articles on the subject.
Rusting, Ricki L. “Why Do We Age?” Scientific American 267 (December, 1992):...
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Gene mutations (Encyclopedia of Genetic Disorders)
In a strict sense, mutations are changes in genes not caused by genetic recombination. A change in the base sequence of DNA, for example, represents a mutational change. Spontaneous mutations are mutations that occur at a given frequency without the need for an inducing agent of change (mutagenic agent). The term mutation is also used in a less technical sense to describe changes in the human genome (i.e., evolution) that result from a broad spectrum of processes that act to increase or decrease genetic variation within a population.
By definition, a gene is a hereditary unit that carries information used to construct proteins via the processes of transcription and translation. The human gene pool is the set of all genes carried within the human population. Genetic changes, including mutations, can be beneficial, neutral or deleterious. In general, mutations, along with recombination and gene flow, act to increase genetic variation (i.e., the number of types of genes or alleles) within the human species.
The term mutation was originally used by Dutch botanist Hugo De Vries (1848935) to describe rapid changes in phenotype from one generation to the next. Subsequently, scientists used the term mutation to describe long-term, multi-generational, and heritable physical changes to genes.
Mutations generally occur via chromosomal...
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Mutation (Encyclopedia of Science)
A mutation is a permanent change in a gene that is passed from one generation to the next. An organism born with a mutation can look very different from its parents. People with albinismhe lack of color in the skin, hair, and eyesave a mutation that eliminates skin pigment. Dwarfs are an example of a mutation that affects growth hormones.
Mutations are usually harmful and often result in the death of an organism. However, some mutations may help an organism survive or be beneficial to a species as a whole. In fact, useful mutations are the driving force behind evolution.
Changes in DNA
Until the mid-1950s, no explanation for the sudden appearance of mutations existed. Today we know that mutations are caused when the hereditary material of life is altered. That hereditary material consists of long, complex molecules known as deoxyribonucleic acid (DNA).
Every cell contains DNA on threadlike structures called chromosomes. Sections of a DNA molecule that are coded to create specific proteins are known as genes. Proteins are chemicals produced by the body that are vital to cell function and structure. Human beings carry about 100,000 genes on their chromosomes. If the structure of a particular gene is altered, that gene will no longer be able to perform the function it is supposed to perform. The protein for which it codes...
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Mutation (Encyclopedia of Science and Religion)
A mutation in a gene is a structural change in the sequence of nucleotide subunits in the chains that make up DNA. Changing the structure of a gene alters the design information contained in its nucleotide sequence, and generally affects the function of that gene's product. The design instructions for that gene product are spelled out in DNA as a particular sequence of the chemical subunits called nucleotides, each of which contains a nitrogenous base: adenine (A), thymine (T), cytosine (C), or guanine (G). Hundreds of nucleotides are linked in a DNA chain in the sequence that spells out instructions for a single gene. This is analogous to conveying instructions in printed books by particular arrangements of twenty-six kinds of alphabetical letters. In the case of genes, however, there are only four letters in the alphabet.
Gene products are usually proteins, and altering the design information in a particular gene will alter the structure and function of its corresponding protein. Since proteins do all the body's work, they account for all the biological characteristics (phenotypes) of any organism. Usually, a mutation in a gene produces a harmful effect, hindering the function of the protein designed by that gene, and sometimes the hindrance is lethal to the organism. Many cancers and inherited diseases are believed to be associated with mutations. In contrast, very occasionally a mutation may be beneficial. If a beneficial mutation is inherited it could cause progeny to adapt better to their environment than their parents could. Such mutations provide a substrate for natural selection in evolving new or better biological functions.
Mutations are produced from errors when cells copy DNA, or from damage caused by radiation or chemicals. Cells contain mechanisms for repairing DNA, but they are not perfect. Changes in the nucleotide sequence can include substitution of one nucleotide for another, insertion or deletion of one or more bases, or transposition of segments of the nucleotide chain.
Although some nucleotide sequences seem more prone to mutation than others, rules governing the specific location of mutations are not evident. The view that genetic variants are produced by chance, and that natural selection favors variants that best meet the necessities of survival, led to the claim that evolution is the product of mere chance and necessity. This claim was extended theologically to assert that there is no purpose in the universe, and therefore no designer, divine or otherwise. Some challenges to this claim are based on different concepts of chance.
There are reports of mutant genes that predispose their bearers to abnormal behaviors, such as violence or addiction. A complication in the interpretation of such reports is that a behavioral gene, like most genes, would be just one of many factors determining the behavior under consideration. In addition to environment, biological history, and cultural influences, those factors would include other genes having functions coordinated with those of the behavioral gene. Nevertheless claims for the existence of such mutant genes as the socalled violence gene have provoked theological discussion about personal culpability on sin.
See also BEHAVIORAL GENETICS; DESIGN; DNA; EVOLUTION; GENETIC DEFECT; GENETIC TESTING; GENETICS
Hefner, Philip. "Determinism, Freedom, and Moral Failure." In Genetics: Issues of Social Justice, ed. Ted Peters. Cleveland, Ohio: Pilgrim Press, 1998.
Kitcher, Philip. The Lives to Come. New York: Simon and Schuster, 1996.
Monod, Jacques. Chance and Necessity. London: Collins, 1972.
Peacocke, Arthur R. "Biological Evolution: A Positive Theological Appraisal." In Evolutionary and Molecular Biology, eds. Robert John Russell, William R. Stoeger, and Francisco J. Ayala. The Vatican and Notre Dame, Ind.: Vatican Observatory and Notre Dame University Press, 1998.
Peters, Ted. "Genes, Theology, and Social Ethics." In Genetics: Issues of Social Justice, ed. Ted Peters. Cleveland, Ohio: Pilgrim Press, 1998.
R. DAVID COLE
Mutations (World of Microbiology and Immunology)
A mutation is any change in genetic material that is passed on to the next generation. The process of acquiring change in genetic material forms the fundamental underpinning of evolution. Mutation is a source of genetic variation in all life forms. Depending on the organism or the source of the mutation, the genetic alteration may be an alteration in the organized collection of genetic material, or a change in the composition of an individual gene.
Mutations may have little impact, or they may produce a significant positive or negative impact, on the health, competitiveness, or function of an individual, family, or population.
Mutations arise in different ways. An alteration in the sequence, but not in the number of nucleotides in a gene is a nucleotide substitution. Two types of nucleotide substitution mutations are missense and nonsense mutations. Missense mutations are single base changes that result in the substitution of one amino acid for another in the protein product of the gene. Nonsense mutations are also single base changes, but create a termination codon that stops the transcription of the gene. The result is a shortened, dysfunctional protein product.
Another mutation involves the alteration in the number of bases in a gene. This is an insertion or deletion mutation. The impact of an insertion or deletion is a frameshift, in which the normal sequence with which the genetic material is interpreted is altered. The alteration causes the gene to code for a different sequence of amino acids in the protein product than would normally be produced. The result is a protein that functions differentlyr not alls compared to the normally encoded version.
Genomes naturally contain areas in which a nucleotide repeats in a triplet. Trinucleotide repeat mutations, an increased number of triplets, are now known to be the cause of at least eight genetic disorders affecting the nervous or neuromuscular systems.
Mutations arise from a number of processes collectively termed mutagenesis. Frameshift mutations, specifically insertions, result from mutagenic events where DNA is inserted into the normally functioning gene. The genetic technique of insertional mutagenesis relies upon this behavior to locate target genes, to study gene expression, and to study protein structure-function relationships.
DNA mutagenesis also occurs because of breakage or base modification due to the application of radiation, chemicals, ultraviolet light, and random replication errors. Such mutagenic events occur frequently, and the cell has evolved repair mechanisms to deal with them. High exposure to DNA damaging agents, however, can overwhelm the repair machinery.
Genetic research relies upon the ability to induce mutations in the lab. Using purified DNA of a known restriction map, site-specific mutagenesis can be performed in a number of ways. Some restriction enzymes produce staggered nicks at the site of action in the target DNA. Short pieces of DNA (linkers) can subsequently be introduced at the staggered cut site, to alter the sequence of the DNA following its repair. Cassette mutagenesis can be used to introduce selectable genes at the specific site in the DNA. Typically, these are drug-resistance genes. The activity of the insert can then be monitored by the development of resistance in the transformed cell. In deletion formation, DNA can be cut at more than one restriction site and the cut regions can be induced to join, eliminating the region of intervening DNA. Thus, deletions of defined length and sequence can be created, generating tailor-made deletions. With site-directed mutagenesis, DNA of known sequence that differs from the target sequence of the original DNA, can be chemically synthesized and introduced at the target site. The insertion causes the production of a mutation of pre-determined sequence. Site-directed mutagenesis is an especially useful research tool in inducing changes in the shape of proteins, permitting precise structure-function relationships to be probed. Localized mutagenesis, also known as heavy mutagenesis, induces mutations in a small portion of DNA. In many cases, mutations are identified by the classical technique of phenotypic identificationooking for an alteration in appearance or behavior of the mutant.
Mutagenesis is exploited in biotechnology to create new enzymes with new specificity. Simple mutations will likely not have as drastic an effect as the simultaneous alteration of multiple amino acids. The combination of mutations that produce the desired three-dimensional change, and so change in enzyme specificity, is difficult to predict. The best progress is often made by creating all the different mutational combinations of DNA using different plasmids, and then using these plasmids as a mixture to transform Escherichia coli bacteria. The expression of the different proteins can be monitored and the desired protein resolved and used for further manipulations.
See also Cell cycle (eukaryotic), genetic regulation of; Cell cycle (prokaryotic), genetic regulation of; Chemical mutagenesis; Chromosomes, eukaryotic; Chromosomes, prokaryotic; DNA (Deoxyribonucleic acid); Laboratory techniques in immunology; Mitochondrial DNA; Mitochondrial inheritance; Molecular biology and molecular genetics