Oxford University Press - Online Resource Centres

Young: Medical Genetics

Online Glossary

A selection of definitions to key medical genetics terms are provided on a complimentary basis below from A Dictionary of Genetics, 7th Edition, Edited by Robert C. King, William D. Stansfield, and Pamela K. Mulligan, Oxford University Press, 2006.
Oxford Reference Online. Oxford University Press. 10 March 2007. www.oxfordreference.com Copyright: © Oxford University Press Inc. 1968, 1972, 1985, 1990, 1997, 2002, 2006, 2007

"See also" entries are given in blue. We trust you find these entries useful. To view these entries in common with the other 7000 entries in the dictionary you may purchase the print or full online version. For further information visit the catalogue page.

[A] [B] [C] [D] [E] [F] [G] [H] [I] [J] [K] [L] [M] [N] [O] [P] [Q] [R] [S] [T] [U] [V] [W] [X] [Y] [Z]


Alu family

the most common dispersed, repeated DNA sequence in the human genome. There are at least 750,000 Alu elements, each consisting of about 300 base pairs, accounting for 11% of human DNA. Each element is made up of two 130 base pair sequences joined head to tail with a 32 base pair insert in the right-hand monomer. Alu sequences are targeted by cohesins (q.v.). The family name is derived from the fact that these sequences are cleaved by restriction endonuclease Alu I. See human gene maps, repetitious DNA .

[Back to top]


bacterial artificial chromosomes (BACs)

cloning vectors derived from the naturally occuring F factor (q.v.) of Escherichia coli (q.v.) and designed to accept large inserts (i.e., those in the size range of 80–350 kilobases). Insert-containing BACs are introduced into E. coli cells by electroporation (q.v.), where they can be maintained as circular plasmids. In contrast to yeast artificial chromosomes (YACs) (q.v.), which can show structural instability of inserts, DNA fragments closed in BACs remain structurally intact. This is because BACs contain F factor regulatory genes that control their replication and maintain their copy number to one or two per cell. The absence of multiple artificial chromosomes in a single cell minimizes sequence rearrangement in inserts by reducing the likelihood of recombination between the inserted fragments. BACs are useful for cloning DNA from large genomes, chromosome walking (q.v.), physical mapping, and shotgun sequencing (q.v.) of complex genomes. See DNA vector, genome, genomic library, kilobase, physical map, plasmid cloning vector, P1 artificial chromosomes (PACs), regulator gene.

binomial distribution

a probability function so named because the probabilities that an event will or will not occur, n, n - 1, n - 2, …, 0 times are given by the successive coefficients in the binomial expansion (a + b)n . Since a and b are the probabilities of occurrence and non-occurrence, respectively, their sum equals 1. The coefficients in a given binomial expansion can be found by referring to Pascal's pyramid (see illustration on page 49).

Binomial distribution (Pascal's pyramid)

Here each horizontal row consists of the coefficients in question for consecutive values of n. The expansions for n equaling 1, 2, 3, 4, or 5 are shown below: (a + b)1 = 1a + 1b (a + b)2 = 1a 2+2ab + 1b 2 (a + b)3 = 1a 3 + 3a 2 b + 3ab 2 + 1b 3 (a + b)4 = 1a 4 + 4a 3 b + 6a 2 b 2 + 4ab 3 + 1b 4 (a + b)5 = 1a 5 + 5a 4 b + 10a 3 b 2 + 10a 2 b 3 + 5 ab 4 + 1b 5 Note that each term of the triangle is obtained by adding together the numbers to the immediate left and right on the line above. Such a binomial distribution can be used for calculating the frequency of families in which a certain proportion of individuals show a given phenotype. If we ask, for example, what will be the distribution of girls and boys in families numbering four children and let the frequency of boys = a, and that of girls = b; then using the formula (a + b)4, we conclude that the distribution would be 1/16 all boys; 4/16 3 boys and 1 girl; 6/16 2 boys and 2 girls; 4/16 1 boy and 3 girls; and 1/16 all girls. Pascal's pyramid is named after its inventor, the French mathematician Blaise Pascal (1623-1662).

[Back to top]


crossing over

the exchange of genetic material between homologous chromosomes. Meiotic crossing over occurs during pachynema and involves the nonsister strands in each meiotic tetrad. Each exchange results in a microscopically visible chiasma (q.v.). In order for proper segregation of homologs at the first meiotic division, each tetrad must have at least one chiasma. For this reason meiotic recombination is enhanced in very short chromosomes. Crossing over can also occur in somatic cells during mitosis. In suitable heterozygotes this may result in twin spots (q.v.). Exchange between sister chromatids can also occur and is a sensitive indicator of DNA damage caused by ionizing radiations and chemical mutagens. Sister chromatid exchanges normally do not result in genetic recombination. See Chronology, 1912, Morgan; 1913, Tanaka; 1931, Stern; 1931, Creighton and McClintock; 1961, Meselson and Weigel; 1964, Holliday; 1965, Clark; 1971, Howell and Stern; 1989, Kaback, Steensma, and De Jonge; 1992, Story, Weber, and Steitz; genetic recombination, Holliday model, human pseudoautosomal region, meiosis, RecA protein, site-specific recombination.

[Back to top]


DNA methylation

the addition of methyl groups to specific sites on a DNA molecule. Between 2 and 7% of the cytosines in the DNA of animal cells are methylated, and the methylated cytosines are found in CG doublets (often called CpG islands). The Cs on both strands of a short palindromic sequence are often methylated, giving a structure
5' *CpG *CpG 3' 3' GpC* GpC* 5'
where asterisks represent methylated sites. Upstream elements that control the expression of genes contain repeated CG doublets that may be methylated or unmethylated. The absence of methyl groups is associated with the ability to be transcribed, while methylation results in gene inactivity. Methylation occurs immediately after replication. Methylation of cytosine prevents transcription, and it has been suggested that methylation is a mechanism that evolved to suppress transcription by transposons and forms of selfish DNA (q.v.). Proteins which recognize CpG islands have been isolated from many animal and plant species. These proteins have a methyl-CpG-binding domain (MBD) that is about 70 amino acids long. Such MBD proteins function as transcription repressors. Some of the genes encoding MBD proteins have been localized in mice and humans. One MBD gene occurs on the X chromosome at the same site in both species. In humans progressive neurologic developmental disorders occur in individuals hemizygous or homozygous for mutations in this gene. See Chronology, 1997, Yoder, Walsh, and Bestor; 2000, Bell and Felsenfeld; H19, 5-methylcytosine (5-mCyt), methyl transferase, parental imprinting, telomeric silencing.

Duffy blood group gene

the first human genetic locus to be localized on a specific autosome. The gene (symbolized FY) is at 1q21-22, and its nucleotide sequence has been determined. The gene encodes a protein that contains 338 amino acids organized into several transmembrane domains. The protein functions as a receptor for various cytokines (q.v.) and for Plasmodium vivax merozoites. Individuals homozygous for mutations that repress the transcription of Duffy gene in erythrocytes resist the invasion of these malaria parasites. Practically all West Africans are Duffy negative. The blood group was named in 1950 after the patient whose blood contained antibodies against the FY gene product. See Chronology, 1968, Donahue et al.; 1976, Miller et al.; Chaudhuri et al.; G proteins, malaria, Mendelian Inheritance in Man (MIM), Plasmodium life cycle.

[Back to top]


fragile chromosome site

a nonstaining gap of variable width that usually involves both chromatids and is always at exactly the same point on a specific chromosome derived from an individual or kindred. Such fragile sites are inherited in a Mendelian codominant fashion and exhibit fragility as shown by the production of acentric fragments and chromosome deletions. In cultured human cells, fragile sites are expressed when the cells are deprived of folate or thymidine or if methotrexate is added to the medium. See folic acid, fragile X-associated mental retardation. http://www.fraxa.org.

[Back to top]


gene conversion

a situation in which the products of meiosis from an AA' individual are 3A and 1A' or 1A and 3A', not 2A and 2A' as is usually the case. Thus, one gets the impression that one A gene has been converted to an A' gene (or vice versa). Gene conversion is thought to involve a rare error in DNA repair that occurs while recombination is going on during meiotic prophase. A double-strand break in one bivalent is enlarged to eliminate one allele of the sister strand. When the gap is repaired, a non-sister strand carrying the alternate allele is used as a template, with the result that the tetrad comes to contain three copies of one allele and one of the other. Therefore gene conversion leads to the unequal recovery of alleles from DNA molecules that each carry a pair of alleles, one normal and one defective. The human Y chromosome contains several palindromes (q.v.) in which are imbedded structural genes that function in spermatogenesis. Within each palindrome, multiple copies of structural genes function as templates for repair of mutated genes. In this way gene conversion prevents the Y from accumulating sterility mutations. See Chronology, 1935, Lindgren; 2003, Skaletsky et al.

[Back to top]



a DNA-binding protein that functions to unwind the double helix. Such unwinding is necessary at replication forks so that DNA polymerases can advance along single strands. Unwinding is also necessary for cut and patch repair (q.v.). Loss of function mutations in genes that encode helicases can result in cancer or premature aging. For example, mutations of genes that encode enzymes belonging to the RecQ family of human DNA helicases cause Bloom syndrome and Werner syndrome (both of which see). See nucleolus, replisome, xeroderma pigmentosum.

[Back to top]


insertional mutagenesis

alteration of a gene as a consequence of inserting unusual nucleotide sequences from such sources as transposons, viruses, transfection, or injection of DNA into fertilized eggs. Such mutations may partially or totally inactivate the gene product or may lead to altered levels of protein synthesis. See insertional inactivation, insertion sequences, transgenic animals.

[Back to top]


leucine zipper

a region in DNA-binding proteins spanning approximately 30 amino acids that contains a periodic repeat of leucines every seven residues. The region containing the repeat forms an alpha helix, with the leucines aligned along one face of the helix. Such helices tend to form stable dimers with the helices aligned in parallel. Leucine zippers occur in a number of transcriptional regulators. See Chronology, 1988, Landschulz et al.; motifs, myc.

[Back to top]


mismatch repair

a system for correcting mismatches between bases in the parent and daughter strands of DNA that make hydrogen bonding impossible. Recognition of the mismatch requires several proteins, including the one encoded by the MSH2 gene. After the segment is cut out, the resulting gap is filled by the actions of DNA polymerase I and DNA ligase (q.v.). See hereditary nonpolyposis colorectal cancer (HNPCC) .

mitotic recombination

a process in which a diploid cell undergoing mitosis gives rise to daughter cells with allele combinations different from that in the parental cell. As in meiotic recombination, mitotic recombination generally involves genetic exchange between chromatids of homologous chromosomes, but occurs less frequently than meiotic recombination. Mitotic recombination can give rise to tissues that are genetic mosaics, including tissues with twin spots (q.v.), and can be experimentally induced. See Chronology, 1936, Stern; gene targeting, homologous recombination, somatic crossing over .

[Back to top]



a cellular gene that functions in controlling the normal proliferation of cells and either (1) shares nucleotide sequences with any of the known viral onc genes, or (2) is thought to represent a potential cancer gene that may become carcinogenic by mutation, or by overactivity when coupled to a highly efficient promoter. Some proto-oncogenes (e.g., c-src) encode protein kinases that phosphorylate tyrosines in specific cellular proteins. Others (e.g., c-ras) encode proteins that bind to guanine nucleotides and possess GTPase activity. Still other oncogenes encode growth factors or growth factor receptors. See maturation promoting factor, Philadelphia (Ph1) chromosome, platelet-derived growth factor.


a gene bearing close resemblance to a known gene at a different locus, but rendered nonfunctional by additions or deletions in its structure that prevent normal transcription and/or translation. Pseudogenes are usually flanked by direct repeats of 10 to 20 nucleotides; such direct repeats are considered to be a hallmark of DNA insertion. Two classes of pseudogenes exist: (1) Traditional pseudogenes (as exemplified in the globin gene families) appear to have originated by gene duplication and been subsequently silenced by point mutations, small insertions, and deletions; they are usually adjacent to functional copies and show evidence of being under some form of selective constraint for several millions of years after their formation. (2) Processed pseudogenes lack introns, possess a remnant of a poly-A tail, are often flanked by short direct repeats, and are usually unassociated with functional copies; all of which suggests their formation by the integration into germ-line DNA of a reverse-transcribed processed RNA. Processed pseudogenes are rare in yeast and Drosophila, but common in mammals. For example, in humans there are 20 pseudogenes that are believed to have arisen from actin and beta tubulin mRNAs. See Chronology, 1977, Jacq et al.; hemoglobin genes, leprosy bacterium, orphons, processed gene.

[Back to top]


restriction endonuclease

any one of many enzymes that cleave foreign DNA molecules at specific recognition sites. Restriction endonucleases are coded for by genes called restriction alleles. The enzymes are named by a symbol that indicates the bacterial species from which they were isolated, followed by a Roman numeral that gives the chronological order of discovery when more than one enzyme came from the same source. Some restriction endonucleases, the organisms from which they were isolated, and their target nucleotide sequences are illustrated on page 384. The arrows indicate the cleavage sites. Note that BamHI and EcoRI cleave the strands of DNA at specific sites four nucleotides apart. Such staggered cleavage yields DNA fragments with protruding 5' termini. Such ends are said to be "sticky" or "cohesive" because they will hydrogen bond to complementary 3' ends. As a result, the end of any DNA fragment produced by an enzyme, such as EcoRI, can anneal with any other fragment produced by that enzyme. This property allows splicing of foreign genes into E. coli plasmids. Enzymes like HindII produce flush or blunt-ended fragments. Restriction endonucleases are used extensively to map DNA regions of interest. See Chronology, 1962, Arber; 1968, Smith et al.; 1970, Smith and Wilcox; 1971, Danna and Nathans; 1972, Mertz and Davis, Hedgpeth et al.;, Individual Databases; Alu family, polylinker site .

[Back to top]



a reverse transcriptase containing an RNA molecule that functions as the template for the telomeric repeat. The first telomerase was isolated from Tetrahymena (q.v.). It is a large ribonucleoprotein complex weighing about 500 kilodaltons. The RNA of the Tetrahymena telomerase contains 159 nucleotides, and its secondary structure is shown in the drawing. The nine specific nucleotides form the templating domain, which is complementary to the G-rich strand of the telomere (q.v.). The functioning of telomerases seems to be activated in dividing embryonic cells and gametocytes. Telomerase function is repressed in differentiated somatic cells but reactivated in cancer cells. In human telomerase, the templating domain is 5'-CUAACCCUAAC-3' and the telomeric repeat is (TTAGGG) n. Antisense RNAs designed to bind with telomerases cause HeLa cells (q.v.) to die after 23 to 26 doublings. See Chronology, 1985, Greider and Blackburn; 1994, Kim et al.; 1995, Feng et al.; RNA-dependent DNA polymerase .

[Back to top]



a gene located in the X chromosome inactivation center of humans at Xq13. The homologous gene in the mouse is symbolized Xist. XIST is the acronym for X-Inactive Specific Transcript, and the major transcript is an RNA molecule about 19 kb long. Shorter transcripts are also generated by alternative splicing (q.v.). The XIST gene is 232,103 base pairs long. The euchromatic part of the X is six times longer than that of the Y. XIST RNA is transcribed in the nuclei of female somatic cells, where it coats the X chromosome and causes its inactivation. The transcribing gene is on the chromosome that is being silenced. Chromosomal regions subject to inactivation are enriched with DNA LINE-1 elements. These L1 elements may serve as targets to which XIST RNAs bind. See Chronology, 1996, Penny et al.; 1998, Lyon; repetitious DNA, X-chromosome inactivation .

[Back to top]


yeast artificial chromosomes (YACs)

genetically engineered circular chromosomes that contain elements from chromosomes contributed by Saccharomyces and segments of foreign DNAs that can be much larger than those accepted by conventional cloning vectors (q.v.). As shown in the diagram on page 480, YACs are generated from synthetic minichromosomes that contain a yeast centromere (C), a replication orgin (RO), and fused telomeres (TL and Tr). In addition, the circular chromosome contains three marker genes (M1, M2, and M3), which when expressed, allow selection of the cells carrying the plasmid and sites 1 and 2, which allow specific restriction endonucleases (q.v.), to break the molecule. Cleavage at 1 opens the ring, while cleavage at 2 generates centric and acentric fragments with ends that will accept foreign DNA fragments. Once these are ligated, an artificial chromosome is generated with a short and a long arm. This contains the spliced segment of foreign DNA to be cloned. Such artificial chromosomes are distributed normally during subsequent yeast divisions, and so colonies containing YACs are generated. In cells possessing the insert, the M1 and M3 markers are expressed, but the damaged M2 is not. So religated YACs can be distinguished from unbroken plasmids. YACs can accept DNA inserts up to 1,000 kilobases long. Compare with bacterial artificial chromosomes (BACs) and P1 artificial chromosomes (PACs). See Chronology, 1987, Burke, Carle, and Olson; DNA vector, kilobase, plasmid cloning vectors .

[Back to top]


zinc finger proteins

proteins possessing tandemly repeating segments that bind zinc atoms. Each segment contains two closely spaced cysteine molecules followed by two histidines.


Each segment folds upon itself to form a fingerlike projection. The zinc atom is linked to the cysteines and histidines at the base of each loop as shown here, where C circles represent cysteine molecules, H circles represent histidine molecules, and unlabeled circles represent the other amino acids of the polypeptide finger. The zinc fingers serve in some way to enable the proteins to bind to DNA molecules, where they regulate transcription. See Chronology, 1985, Miller et al.; 1987, Page et al.; androgen receptor (AR), motifs, transcription factors, vitamin D receptor (VDR), Wilms tumor .

[Back to top]