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Strachan T, Read AP. Human Molecular Genetics. 2nd edition. New York: Wiley-Liss; 1999.

Cover of Human Molecular Genetics

Human Molecular Genetics. 2nd edition.

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5′ add-on mutagenesis

a form of PCR mutagenesis in which the 5′ end of a primer is designed to introduce into the amplification product a DNA sequence not present in the target DNA. See Figure 6.20.


one of several alternative forms of a gene or DNA sequence at a specific chromosomal location (locus). At each autosomal locus an individual possesses two alleles, one inherited from the father and one from the mother.

Allele-specific oligonucleotide (ASO)

a synthetic oligonucleotide, often about 20 bases long, which hybridizes to a specific target sequence and whose hybridization can be disrupted by a single base pair mismatch under carefully controlled conditions. ASOs are often labeled and used as allele-specific hybridization probes (see Figure 6.9), or as allele-specific primers in PCR. See ARMS.

Allelic association

particular alleles at two or more neighboring loci show allelic association if they occur together with frequencies significantly different from those predicted from the individual allele frequencies. Often called linkage disequilibrium.

Allelic exclusion

the mechanism whereby only one of the two immunoglobulin alleles in B lymphocytes, or T-cell receptor alleles in T lymphocytes, is expressed. More generally, any naturally occurring mechanism that causes only one allele to be expressed – see Box 8.6.

Alphoid DNA (or -satellite DNA)

a class of satellite DNA with an average repeat length of about 170 bp; found at centromeres. See Section 7.4.1.

Alternative splicing

the natural use of different sets of splice junction sequences to produce more than one product from a single gene. See Section 8.3.2, Box 8.4.


PCR using a primer that anneals to Alu repeats to amplify DNA located between two oppositely oriented Alu sequences. Used as a method of obtaining a fingerprint of bands from an uncharacterized human DNA. See Figure 10.18.


PCR primers.

Anchored PCR

PCR where one primer anneals to an oligonucleotide linker which has been ligated onto the end of an uncharacterized DNA fragment. See Figures 6.12, 6.13.


a chromosome constitution with one or more chromosomes extra or missing from a full euploid set.


the association of complementary DNA (or RNA) strands to form a double helix.

Anonymous DNA

DNA not known to have a function.


a phenomenon in which the age of onset of a disorder is reduced and/or the severity of the phenotype is increased in successive generations. Characteristic of dynamic mutations.


the 3-base sequence in a tRNA molecule that base-pairs with the codon in mRNA. See Figures 1.7B,1.20, Table 1.5.

Antisense oligonucleotide

a synthetic oligonucleotide designed to be complementary to a naturally occurring mRNA molecule. Formation of a double helix can prevent expression of the mRNA. See Section 22.3.2.

Antisense RNA

a transcript from the antisense strand of a gene. Naturally occurring antisense RNAs may negatively regulate gene expression.

Antisense strand (template strand)

the DNA strand of a gene which, during transcription, is used as a template by RNA polymerase for synthesis of mRNA. See Figure 1.12.


programmed cell death.

Archaeon (pl. archaea)

a single-celled prokaryote superficially resembling a bacterium, but with molecular features indicative of a third kingdom of life. See Box 14.1.

ARMS (Amplification refractory mutation system)

allele-specific PCR. See Figure 6.9.

Assortative mating

marriage between people of similar phenotype or genotype (e.g. tall people tend to marry tall people, deaf people tend to marry deaf people; some people prefer to marry relatives). Assortative mating can produce a non-Hardy–Weinberg distribution of genotypes in a population.

Autonomously replicating sequence (ARS)

in yeast, a DNA sequence having an origin of replication. See Figure 2.8, Section 4.3.4.


any chromosome other than the sex chromosomes, X and Y.


in an inbred person, homozygosity for alleles identical by descent.

Autozygosity mapping

a form of genetic mapping for autosomal recessive disorders in which affected individuals are expected to have two identical disease alleles by descent. See Figure 11.8.

Bacterial artificial chromosome (BAC)

a recombinant plasmid in which inserts up to 300 kb long can be propagated in bacterial cells. See Section 4.3.3.

Barr body (sex chromatin)

a blob of condensed chromatin visible at the edge of the nucleus in some interphase cells of females that represents the inactive X chromosome.

Bias of ascertainment

distortions in a set of data caused by the way cases are collected – for example, severely affected people are more likely to be ascertained than mildly affected people. See Section 19.4.1.

Biological fitness

see Fitness.


the very high affinity of streptavidin for biotin allows biotin-labeled molecules to be isolated efficiently from a mixture. See, for example, Figure 10.24.


the four-stranded structure seen in prophase I of meiosis, comprising two synapsed homologous chromosomes. See Figure 2.14.


a family of programs that search sequence databases for matches to a query sequence. See Section 20.1.4.


a DNA fragment having no single-stranded extensions.

Boundary elements

sequences that define the boundaries of coordinately regulated chromatin domains in chromosomes. See Box 8.2.

Branch site

in mRNA processing, a rather poorly defined sequence (consensus CTRAY; R = purine, Y = pyrimidine) located 10–50 bases upstream of the splice acceptor, containing the adenosine at which the lariatsplicing intermediate is formed. See Figure 1.15.

Bubble-linker PCR (vectorette-PCR)

a form of anchored PCR that uses a linker containing an unpaired region (vectorette) to amplify adjacent uncharacterized sequences. See Figure 10.16.


a specialized chemical group that cells add to block the 5′ end of mRNA. See Figure 1.17.

cDNA (complementary DNA)

DNA synthesized by the enzyme reverse transcriptase using mRNA as a template, both experimentally (see Figures 4.8 and 6.5) or in vivo (see Figures 7.13 and 14.18).

cDNA selection

a hybridization-based method for retrieving genomic clones that have counterparts in a cDNA library. See Figure 10.24.

CentiMorgan (cM)

a unit of genetic distance equivalent to a 1% probability of recombination during meiosis. See Figure 11.3 for the correspondence between genetic and physical distances.

CentiRay (cR)

a mapping unit when using radiation hybrids, which is dependent on the intensity of the irradiation. A distance of 1 cR8000 represents 1% frequency of breakage between two markers after exposure to a dose of 8000 rad. See Figure 10.3.

Central dogma

a summary of the usual information flow in organisms, from DNA to RNA to protein.

Centric fusion

strictly, formation of an abnormal chromosome by fusion of two chromosome arms at the centromeres. Loosely applied to the common human Robertsonian translocations, which are in fact produced by exchange between the proximal short arms of acrocentric chomosomes (Figure 2.21).


the primary constriction of a chromosome, separating the short arm from the long arm, and the point at which spindle fibers attach to pull chromosomes apart during cell division. See Section 2.3.2.

Chiasma (pl. chiasmata)

a visible crossover between paired homologous chromosomes in prophase I of meiosis. See Figure 2.14.


an organism derived from more than one zygote. See Figure 3.9.

Chimeric insert

a clone insert consisting of two or more originally noncontiguous DNA sequences.


from the end of S phase of the cell cycle (Figure 2.2) until anaphase of cell division, chromosomes consist of two sister chromatids. Each contains a complete double helix and the two are exact copies of each other.

Chromatin fiber

the 30 nm coiled coil of DNA and histones that is believed to be the basic conformation of chromatin. See Figure 2.7.

Chromosome painting

fluorescence labeling of a whole chromosome by a FISH procedure in which the probe is a cocktail of many different DNA sequences from a single chromosome. See Box 10.2.

Chromosome walking

a method of isolating sequences adjacent on the chromosome to a characterized clone. See Figure 10.14.


cis-acting regulatory sequences control the activity of a gene only when it is part of the same DNA molecule or chromosome.

Clone fingerprinting

involves generating a pattern of fragments from a clone by restriction digestion or Alu-PCR (Figure 10.20).

Coding DNA

DNA that encodes the amino acid sequence of a polypeptide, or a functional mature RNA which does not specify a polypeptide (see Table 7.4).


a nucleotide triplet (strictly in mRNA, but by extension, in genomic coding DNA) that specifies an amino acid or a translation stop signal. See Figure 1.22.

Coefficient of selection (s)

s = 1 - f, where f is the biological fitness of a genotype.

Comparative genome hybridization (CGH)

use of competitive fluorescence in situ hybridization to detect chromosomal regions that are amplified or deleted, especially in tumors. See Figure 18.5.


bacterial cells in a competent state are able to take up high molecular weight DNA.

Complementary strands

two nucleic acid strands are said to be complementary in sequence if they can form sufficient base pairs so as to generate a stable double-stranded structure.


two alleles complement if in combination they restore the wild-type phenotype (see Box 3.2). Normally, alleles complement only if they are at different loci, although some cases of interallelic complementation occur.


multiple copies of the same sequence joined tandemly end to end.

Concerted evolution

the process whereby individual members of a DNA family within one species are more closely related to each other than to members of the same type of DNA family in other species. See Figure 14.15.

Conditional knock-out

an engineered mutant that causes loss of gene function under some circumstances (for example, raised temperature), or in some cells, but not others. See Section 21.3.2.

Congenic strains

strains of a laboratory animal that are identical except at one specific locus (Box 15.4).

Conservation of synteny

when genetic maps of two organisms are compared, synteny is conserved if loci that are located on the same chromosome in one organism are also located together on a single chromosome in the other. See Figure 15.11.

Conservative substitution

a mutation causing a codon to be replaced by another codon that specifies a different amino acid, but one which is related in chemical properties to the original amino acid.


an abnormality or a mutation of a genotype that was present in the fertilized egg, and is therefore present in all cells of a person.

Constitutive expression

a state where a gene is permanently active. Mutations that result in inappropriate constitutive expression are often pathogenic.

Constitutive heterochromatin

chromatin that is always heterochromatic (principally at centromeres of chromosomes).


a list or diagram showing an ordered arrangement of cloned overlapping fragments that collectively contain the sequence of an originally continuous DNA strand.

Contiguous gene (segmental aneusomy) syndrome

a syndrome caused by deletion of a contiguous set of genes, several or all of which contribute to the phenotype (see Section 16.8.1).

Continuous character

a character like height, which everybody has, but to a differing degree – as compared to a dichotomous character like polydactyly, which some people have and others do not have.

Copy number

the number of different copies of a particular DNA sequence in a genome.


a vector constructed by inserting the cos sequences of lambda phage into a plasmid. Permits cloning of inserts 30–46 kb long. See Figure 4.14.

Cot-1 DNA

a fraction of DNA consisting largely of highly repetitive sequences. Obtained from total genomic DNA by selecting for rapidly reassociating DNA sequences during renaturation of DNA. See Box 5.3.

CpG dinucleotide

the sequence 5′ CG 3′ within a longer DNA molecule. CpG dinucleotides are targets of a specific DNA methylation system in mammals that is important in control of gene expression.

CpG island

short stretch of DNA, often <1 kb, containing frequent unmethylated CpG dinucleotides. CpG islands tend to mark the 5′ ends of genes. See Box 8.5.

Cre-lox system

A technique for generating predefined chromosomal deletions. Cre is a bacteriophage P1 gene whose product facilitates recombination between loxP sequences. So called because it creates recombination. See Figures 4.15 and 21.8.

Cryptic splice site

a sequence in pre-mRNA with some homology to a splice site. Cryptic splice sites may be used as splice sites when splicing is disturbed or after a base substitution mutation that increases the resemblance to a normal splice site. See Figure 9.11.

Degenerate oligonucleotides (or primers)

a panel of synthetic oligonucleotides designed so that collectively they correspond to various codon permutations for a given sequence of amino acids.


dissociation of complementary strands to give single-stranded DNA and/or RNA.

Dichotomous character

a character like polydactyly, which some people have and others do not have – as opposed to a continuous character like height, which everybody has, but to differing degree.

Dideoxynucleotides (ddNTPs)

synthetic nucleotides lacking 2′ and 3′ hydroxyl groups. They act as chain terminators during DNA replication. See Figure 6.15.

Differential display

see mRNA differential display.


having two copies of each type of chromosome; the normal constitution of most human somatic cells.

Displacement (D) loop region

in mitochondrial DNA, a short triple-stranded region. See Figure 7.2.

DNA chip

a microarray of oligonucleotides or cDNA clones fixed on a glass surface. They are commonly used in a form of reverse hybridization assay to test for sequence variation in a known gene, or to profile gene expression in an mRNA preparation. See Figures 5.20 and 20.6.

DNA fingerprinting

a method which produces a pattern of hybridizing bands in a Southern blot that can be used to identify a person for legal or forensic purposes (Figure 17.19).

DNA footprinting

see Footprinting.

DNA ligase

an enzyme able to form a phosphodiester bond between adjacent but unlinked nucleotides in a double helix. See also Ligation.

DNA profiling

using genotypes at a series of polymorphic loci to recognize a person, usually for legal or forensic purposes. See Section 17.4.

DNAse I-hypersensitive sites

regions of chromatin that are rapidly digested by DNAse I. They are believed to be important long-range control sequences. See Section 8.5.2.


(in human genetics) describes any trait that is expressed in a heterozygote. See also Semi-dominant.

Dominant negative mutation (antimorph)

a mutation which results in a mutant gene product that can inhibit the function of the wild-type gene product in heterozygotes. See, for example, Figure 16.4.

DOP-PCR (degenerate oligonucleotide primer PCR)

PCR using a mixture of closely related oligonucleotides rather than a single species as primer. See Figure 6.11.

Dosage compensation

any system that equalizes the amount of product produced by genes present in different numbers. In mammals, describes the X-inactivation mechanism that ensures equal amounts of X-encoded gene products in XX and XY cells. See Figure 2.6.

Dot-matrix analysis

a technique for comparing two DNA sequences. See Figure 20.3.


in the 3′ direction when a gene sequence is written in the conventional way (showing the sense strand, in the 5′ to 3′ direction).

Duplicative (copy or replicative) transposition

transposition of a copy of a DNA sequence while the original remains in place.

Dynamic mutation

an unstable expanded repeat that changes size between parent and child. See Box 16.7.

Ectopic transcription

see Illegitimate transcription.

Embryonic stem cells (ES cells)

undifferentiated, pluripotent cells derived from an embryo. Mouse ES cell lines are commonly used as a vehicle for transferring foreign DNA into the germline in order to generate transgenic mice. See Section 21.3.

Empiric risks

risks calculated from survey data rather than from genetic theory. Genetic counseling in most nonmendelian conditions is based on empiric risks. See Section 3.4.4.


a set of short sequence elements which stimulate transcription of a gene and whose function is not critically dependent on their precise position or orientation. See Box 8.2.


heritable (from mother cell to daughter cell, or sometimes from parent to child), but not produced by a change in DNA sequence. DNA methylation is the best understood mechanism.


any DNA sequence that can exist in an autonomous extra-chromosomal form or can be integrated into the chromosomal DNA of the cell. Often used to describe self-replicating and extra-chromosomal forms of DNA.


a part of an antigen with which a particular antibody reacts. See Box 20.2.

ES cells

see Embryonic stem cells.


see Expressed sequence tag.


the fraction of the nuclear genome which contains transcriptionally active DNA and which, unlike heterochromatin, adopts a relatively extended conformation.


‘improving’ a population by selective breeding from the ‘best’ types (positive eugenics) or preventing ‘undesirable’ types from breeding (negative eugenics).


an animal or plant, having cells with a membrane-bound nucleus and organelles. May be multicellular (e.g. metazoa) or unicellular (protist). See Figure 2.1.


the state of having one or more complete sets of chromosomes with none extra or missing; the opposite of aneuploidy.

Exclusion mapping

genetic mapping with negative results, showing that the locus in question does not map to a particular location. Particularly useful for excluding a possible candidate gene without the labor of mutation screening.


a segment of a gene that is represented in the mature RNA product. Individual exons may contain coding DNA and/or noncoding DNA (untranslated sequences). See Figures 1.14 and 1.19.

Exon shuffling

evolution of a gene by combining exons from other pre-existing genes. See Figures 14.17 and 14.18.

Exon skipping

alternative splicing in which splice junction sites that are normally used in RNA splicing are by-passed. See Figure 9.11.

Exon trapping

a technique for detecting sequences within a cloned genomic DNA that are capable of splicing to exons within a specialized vector. See Figure 10.23.

Expressed pseudogene

a copy of a gene that is transcribed but not functional. See Box 7.3.

Expressed sequence tag (EST)

a short (typically 100–300) bp partial cDNA sequence. See Section 13.2.3.

Expression cloning

cloning of cDNAs in specialized vectors permitting expression of a gene product from the insert. See Section 4.4.2.

FACS (fluorescence activated cell sorter)

a machine that can separate cells, or individual chromosomes in suspensions, according to their ability to bind fluorescent dyes. Used, among other purposes, for flow cytometry. See Figure 10.7.

Facultative heterochromatin

chromatin that may exist as euchromatin or heterochromatin, depending on the state of the cell.


see Fluorescence in situ hybridization.

Fitness (f)

in population genetics, a measure of the success in transmitting genotypes to the next generation. Also called biological fitness or reproductive fitness. f always lies between 0 and 1.

Flow cytometry (flow sorting)

fractionation of individual chromosomes according to size and base composition in a fluorescence-activated chromosome (or cell) sorter. See Figure 10.7.

Fluorescence in situ hybridization (FISH)

in situ hybridization using a fluorescently labeled DNA or RNA probe. A key technique in modern molecular genetics – see Figures 5.17, 10.5 and 10.6.


a fluorescent chemical group, used for labeling probes etc. See Box 5.2.


a method of identifying sequences within a cloned DNA molecule that can specifically bind protein molecules, such as transcription factors. See Figure 20.14.

Founder effect

high frequency of a particular allele in a population because the population is derived from a small number of founders, one or more of whom carried that allele.

Frameshift mutation

a mutation that alters the normal translational reading frame of a mRNA by adding or deleting a number of bases that is not a multiple of three.

Functional genomics

analysis of gene function on a large scale, by conducting parallel analyses of gene expression/function for large numbers of genes, even all genes in a genome.

Fusion (hybrid) gene

a gene containing coding sequence from two different genes, usually created by unequal crossover (Figure 9.17) or chromosomal translocations (Figure 18.7A).

Fusion protein

the product of a natural or engineered fusion gene a single polypeptide chain containing amino acid sequences that are normally part of two or more separate polypeptides. See Box 20.2.

Gain-of-function mutation

a mutation that causes inappropriate expression or function of the gene product, rather than simply loss of function. See Sections 16.3, 16.5.

Gene conversion

a naturally occurring nonreciprocal genetic exchange in which a sequence of one DNA strand (acceptor sequence) is altered to become identical to the sequence of another DNA strand (donor sequence). See Figures 9.10 and 9.17.

Gene dosage

the number of copies of a gene. Abnormal dosage of some genes (dosage-sensitive genes) can cause developmental abnormalities. See Sections 16.4.3 and 16.5.2.

Gene frequency

the proportion of all alleles at a locus that are the allele in question. See Section 3.3. Strictly the term should be allele frequency, but the use of gene frequency is too well established now to change.

Gene pool

the totality of genes, either alleles at a given locus or over all loci, in a population.

Gene targeting

a form of in vivo mutagenesis whereby the sequence of a predetermined gene is selectively modified within an intact cell. See Section 21.3.

Gene trap

a method of selecting transgene insertions that have occurred into a gene. See Figure 21.10.

Genetic distance

distance on a genetic map, defined by recombination fractions and the mapping function, and measured in centiMorgans. See Section 11.1.

Genetic enhancement

the possible application of molecular genetic technologies to alter the human germ line and as a result alter the normal phenotype in some way that is considered to be beneficial.

Genetic load

the relative decrease in the average fitness, compared to what it would be if all individuals had the fittest genotype, i.e. (wmax - wav)/wmax . Genetic load is made up of mutational load and segregational load.

Genetic redundancy

performance of the same function in parallel by genes at more than one locus, so that loss of function mutations at one locus do not cause overall loss of function.


the total genetic complement of an organism or virus. For cellular organisms, the set of different DNA molecules, e.g. the human genome comprises 25 different DNA molecules (see Table 7.1).

Genome-wide p value

in testing for linkage or association, the probability on the null hypothesis of observing the statistic in question anywhere in a screen of the whole genome – see also pointwise p value. See Section 11.3.4.


the genetic constitution of an individual, either overall or at a specific locus.

Germ cells (or gametes)

sperm cells and egg cells.

Germ line

the germ cells and those cells which give rise to them; other cells of the body constitute the soma.

Germinal (gonadal or gonosomal) mosaic

an individual who has a subset of germ line cells carrying a mutation that is not found in other germ line cells. See Figure 3.8.


describing a cell (typically a gamete) which has only a single copy of each chromosome (i.e. 23 in man).


a locus shows haploinsufficiency if producing a normal phenotype requires more gene product than the amount produced by a single copy. See Section 16.4.3 and Table 16.2.


a series of alleles found at linked loci on a single chromosome.

Hardy–Weinberg distribution

the simple relationship between gene frequencies and genotype frequencies that is found in a population under certain conditions. See Box 3.3.


DNA methylation on only one strand of the double helix. A transient state occurring after DNA replication. Hemimethylation allows proof-reading enzymes to work out which strand is the original when they find a replication error. See Figures 8.17 and 18.17.


having only one copy of a gene or DNA sequence in diploid cells. Males are hemizygous for most genes on the sex chromosomes. Deletions occurring on one autosome produce hemizygosity in males and in females.


the proportion of the causation of a character that is due to genetic causes. See Box 19.3 and Figure 19.5 for examples of how heritability is calculated.


a chromosomal region that remains highly condensed throughout the cell cycle and shows little or no evidence of active gene expression. See Figure 2.18.


double-stranded DNA in which there is some mismatch between the two strands. See Section 17.1.4 for methods of detecting heteroduplexes.


mosaicism, usually within a single cell, for mitochondrial DNA variants. See Section 3.1.5 and Box 9.3.


an individual is heterozygous at a locus if (s)he has two different alleles at that locus.

Heterozygote advantage

the situation when somebody heterozygous for a mutation has a reproductive advantage over the normal homozygote. Sometimes called overdominance. Heterozygote advantage is the reason why several severe recessive diseases remain common (Box 3.6).

Homologous chromosomes (homologs)

the two copies of a chromosome in a diploid cell. Unlike sister chromatids, homologous chromosomes are not copies of each other; one was inherited from the father and the other from the mother.

Homologous genes (homologs)

two or more genes whose sequences are significantly related because of a close evolutionary relationship, either between species (orthologs) or within a species (paralogs).


of a cell or organism, having all copies of the mitochondrial DNA identical. See Box 9.3.


an individual is homozygous at a locus if (s)he has two identical alleles at that locus. The exact meaning depends on the stringency with which identity is established. For clinical purposes a person is often described as homozygous AA or aa if they have two normally functioning or two pathogenic alleles, regardless of whether they are in fact completely identical. Homozygosity for alleles identical by descent is called autozygosity.


a sequence associated with an abnormally high frequency of recombination or mutation.

Housekeeping gene

a gene whose expression is essential for the function of most or all types of cell.

Hybrid cell panel

a collection of somatic cell hybrids or radiation hybrids used for physical mapping.

Hybridization assay

testing for the presence of a given sequence in a DNA or RNA sample by mixing single DNA (or RNA) strands from a known probe with those of the poorly characterized target sample, then allowing complementary strands to anneal. See Box 5.4.

Hybridization stringency

the degree to which mismatches are tolerated in a hybridization assay. High stringency is achieved by using a high temperature and low salt concentration.

Identity by descent (IBD)

alleles in an individual or in two people that are identical because they have both been inherited from the same common ancestor, as opposed to identity by state.

Identity by state (IBS)

coincidental possession of alleles that appear identical. The alleles may or may not be truly identical. See Figure 12.1.

Illegitimate (ectopic) transcription

low-level transcription of a gene in a cell in which the gene is not normally expressed. Probably a near-universal phenomenon.


determination of the expression of a gene by its parental origin. See Section 8.5 and Box 16.6.

In situ hybridization

hybridization of a labeled nucleic acid to a target DNA or RNA which is typically immobilized on a microscopic slide.

In vitro mutagenesis

introduction of a predefined mutation into a cloned sequence. See Figures 6.19 and 6.20.


marrying a blood relative. The term is comparative, since ultimately everybody is related. The coefficient of inbreeding is the proportion of a person’s genes that are identical by descent.

Informative meiosis

in linkage analysis, a meiosis is informative if the genotypes in the pedigree allow us to decide whether it is recombinant or not (for a given pair of loci). See Box 11.2.

Insertional inactivation

inactivation of a gene by insertion of a foreign DNA sequence within it – a transposon (Figure 7.16) or a transgene (Figure 21.1), for example. See Section 9.5.6.


see Boundary element.


in meiosis, the tendency of one crossover to inhibit further crossing-over within the same region of the chromosomes. See Section 11.1.3.


all the time in the cell cycle when a cell is not dividing.


noncoding DNA which separates neighboring exons in a gene. During gene expression introns are transcribed into RNA but then the intron sequences are removed from the pre-mRNA by splicing (see Figure 1.14). Can be classified according to the mechanism of splicing or, if separating coding DNA sequences, their precise location within codons (see Box 14.3).


an abnormal symmetrical chromosome, consisting of two identical arms, which are normally either the short arm or the long arm of a normal chromosome.


alternative forms of a protein/ enzyme.


an image showing the chromosomes of a cell sorted in order and arranged in pairs, such as Figure 2.17.


a summary of the chromosome constitution of a cell or person, such as 46,XY. See Boxes 2.5 and 2.6 for nomenclature.

Knock-in mutation

a targeted mutation that replaces activity of one gene by that of an introduced gene (usually an allele). See Figure 21.6.

Knock-out mutation

the targeted inactivation of a gene within an intact cell.

Lagging strand

in DNA replication, the strand that is synthesized as Okazaki fragments (see Figure 1.9).

Leading strand

in DNA replication, the strand that is synthesized continuously (see Figure 1.9).


a collection of clones. See Figures 4.7 and 4.8.


see DNA ligase.


formation of a 3′–5′ phosphodiester bond between nucleotides at the ends of two molecules (intermolecular ligation) or the two ends of the same molecule (intramolecular ligation, cyclization).

LINE (long interspersed nuclear element)

a class of repetitive DNA sequences that make up about 10% of the human genome (Table 7.12). Some are active transposable elements. See Figures 7.16 and 7.18.


the tendency of genes or other DNA sequences at specific loci to be inherited together as a consequence of their physical proximity on a single chromosome.

Linkage disequilibrium

see allelic association.

Linker (or adaptor oligonucleotide)

a double-stranded oligonucleotide which is ligated to a DNA fragment of interest to assist cloning or PCR amplification. See, for example, Figures 6.12 and 20.7.


a synthetic lipid membrane designed to transport a molecule of interest into a cell. See Figure 22.6.


a unique chromosomal location defining the position of an individual gene or DNA sequence.

Locus control region (LCR)

a stretch of DNA containing regulatory elements which control the expression of genes in a gene cluster that may be located tens of kilobases away. See Figure 8.23.

Locus heterogeneity

determination of the same disease or phenotype by mutations at different loci. A major problem for linkage analysis. See Section 3.1.4.

Lod score (z)

a measure of the likelihood of genetic linkage between loci. The log (base 10) of the odds that the loci are linked (with recombination fraction q) rather than unlinked. For a mendelian character, a lod score greater than +3 is evidence of linkage; one that is less than -2 is evidence against linkage. See Box 11.3 and Figure 11.5.

Manifesting heterozygote

a female carrier of an X-linked recessive condition who shows some clinical symptoms, presumably because of skewed X-inactivation. See Section 3.1.2.

Mapping function

a mathematical equation describing the relation between recombination fraction and genetic distance. The mapping function depends on the extent to which interference prevents close double recombinants. See Section 11.1.3.


a genetic marker is a polymorphic DNA or protein sequence deriving from a single chromosomal location, which is used in genetic mapping. See Box 12.1. A marker chromosome is an extra chromosome of unidentified origin.

Matrilineal inheritance

transmission from just the mother, but to children of either sex; the pattern of mitochondrial inheritance. See Figure 3.4.

Mean heterozygosity

of a marker, the likelihood that a randomly selected person will be heterozygous. A measure of the usefulness of the marker for linkage analysis (see Section 11.2.2).


of a pedigree pattern, conforming to one of the archetypic patterns shown in Figure 3.2; a character will give a mendelian pedigree pattern if it is determined at a single chromosomal location, regardless of whether or not the determinant is a gene in the molecular geneticist’s sense.


the stage of cell division (mitosis or meiosis) when chromosomes are maximally contracted and lined up on the equatorial plane (metaphase plate) of a cell. See Figures 2.10, 2.11 and 2.15.

Metazoon (pl. metazoa)

a multicellular animal as opposed to a unicellular protozoon.


see DNA chip.


small run (usually less than 0.1 kb) of tandem repeats of a very simple DNA sequence, usually 1–4 bp, for example (CA) n . The primary tool for genetic mapping during the 1990s. See Figures 6.7 and 6.8.

Microsatellite instability

a phenomenon characteristic of certain tumor cells, where during DNA replication the repeat copy number of microsatellites is subject to random changes. Abbreviated to MIN, MSI or RER (replication error). See Figure 18.11.

MIM number

the catalog number for a gene or mendelian character, as listed in Victor McKusick’s Mendelian Inheritance in Man, available as a book and electronically (OMIM).

Minisatellite DNA

an intermediate size array (often 0.1–20 kb long) of short tandemly repeated DNA sequences. See Table 7.11. Hypervariable minisatellite DNA is the basis of DNA fingerprinting and many VNTR markers.

Mismatch repair

a natural enzymic process that replaces a mis-paired nucleotide in a DNA duplex (most likely present because of an error in DNA replication) to obtain perfect Watson–Crick base-pairing. See Figure 18.17.

Missense mutation

a nucleotide substitution that results in an amino acid change. See Box 9.2.

Modifier gene

a gene whose expression can influence a phenotype resulting from mutation at another locus. See Section 16.6.3.

Monoallelic expression

expression of only one of the two copies of a gene in a cell, because of X-inactivation, imprinting or other epigenetic change, or because of the gene rearrangements that take place with immunoglobulin and T-cell receptor genes. See Box 8.6 for examples.

Monoclonal antibody (mAb)

pure antibodies with a single specificity, produced by hybridoma technology, as distinct from polyclonal antibodies that are raised by immunization. See Box 20.2.


an individual who has two or more genetically different cell lines derived from a single zygote. The differences may be point mutations, chromosomal changes, etc. See Figure 3.9.

mRNA differential display

a PCR-based technique for comparing the mRNA species that are expressed in two related sources of cells to pick out differentially expressed genes. See Figure 20.8.

Multigene family

a set of evolutionarily related loci within a genome, at least one of which can encode a functional product. See Section 7.3.

Mutational load

the loss of fitness in a population due to deleterious recessive mutations. The mutational load and the segregational load (due to loss of homozygotes where there is heterozygote advantage) are the two components of the genetic load.

Mutator gene

a gene with an error-checking function. When such a gene is disabled by mutation, there is a general increase in the mutation rate in a cell. See Section 18.7.1.


failure of chromosomes (sister chromatids in mitosis or meiosis II; paired homologs in meiosis I) to separate (disjoin) at anaphase. The major cause of numerical chromosome abnormalities. See Section 2.6.2.

Nonhomologous recombination

recombination between sequences that either have no homology or have limited local homology. A major cause of insertions and deletions, at the genetic or chromosomal level. See for example Figures 9.7 and 16.2.


the situation when somebody carrying an allele that normally causes a dominant phenotype does not show that phenotype. Due to the effect of other genetic loci or of the environment. A pitfall in genetic counseling. Figure 3.5B shows an example.

Nonsense mutation

a mutation that occurs within a codon and changes it to a stop codon. See Box 9.2.

Northern blot

a membrane bearing RNA molecules that have been size-fractionated by gel electrophoresis, used as a target for a hybridization assay. See Figure 5.13.

Nucleolar organizer region (NOR)

the satellite stalks of human chromosomes 13, 14, 15, 21 and 22. NORs contain arrays of ribosomal DNA genes and can be selectively stained with silver. Each NOR forms a nucleolus in telophase of cell division; the nucleoli fuse in interphase.


a structural unit of chromatin. See Figure 2.7.


determined by a small number of genes acting together.


On-line Mendelian Inheritance in Man, the central database of human genes and mendelian characters (http//www.ncbi.nlm.nih.gov/omim/ or http//www.hgmp.mrc.ac.uk/omim/). MIM numbers are the index numbers for entries in OMIM.


a gene involved in control of cell proliferation which, when overactive can help to transform a normal cell into a tumor cell. See Table 18.2. Originally the word was used only for the activated forms of the gene, and the normal cellular gene was called a proto-oncogene, but this distinction is now widely ignored.

Open reading frame (ORF)

a significantly long sequence of DNA in which there are no termination codons in at least one of the possible reading frames. Six reading frames are possible for a DNA duplex because each strand can have three reading frames. See Section 20.1.4.


one of a set of homologous genes in different species (e.g. PAX3 in humans and Pax3 in mice). See Box 14.2.


phenotypes showing heterozygote advantage. A term used in population genetics.


a DNA sequence such as ATCGAT that reads the same when read in the 5′[implies]3′ direction on each strand. DNA–protein recognition, for example by restriction enzymes, often relies on palindromic sequences.

Paracentric inversion

inversion of a chromosomal segment that does not include the centromere. See Figure 2.20.


one of a set of homologous genes within a single species. See Box 14.2.

Partial digestion

digestion, usually of DNA by a restriction enzyme, that is stopped before all target sequences have been cut. The object is to produce overlapping fragments. See Figure 4.7.


the frequency with which a genotype manifests itself in a given phenotype.

Pericentric inversion

inversion of a chromosomal segment that includes the centromere. See Figure 2.20.

Phage display

an expression cloning method in which foreign genes are inserted into a phage vector and are expressed to give polypeptides that are displayed on the surface (protein coat) of the phage. See Figure 20.17.


of linked markers – the relation (coupling or repulsion) between alleles at two linked loci. If allele A1 is on the same physical chromosome as allele B1, they are in coupling; if they are on different parental homologs they are in repulsion. See Figure 11.4. Of the cell cycle – G1, S, G2, M and G0 phases (see Figure 2.2). Of an intron – a term used to classify introns in coding sequences according to the position at which they interrupt the message (see Box 14.3).


the observable characteristics of a cell or organism, including the result of any test that is not a direct test of the genotype.

Physical distance

distance between genes or sequences measured in kilobases, megabases or (in radiation hybrid mapping) centiRays.

Physical mapping

a method of mapping genes or DNA sequences on a chromosome which does not rely on meiotic segregation (genetic mapping).

Point mutation

a mutation causing a small alteration in the DNA sequence at a locus. The meaning is a little imprecise when being compared to chromosomal mutations, the term ‘point mutation’ might be used to cover quite large (but submicroscopic) changes within a single gene, whereas when mutations at a single locus are being discussed, ‘point mutations’ would mean the substitution, insertion or deletion of just a single nucleotide.

Pointwise p value

in linkage analysis, the probability on the null hypothesis of exceeding the observed value of the statistic at one given position in the genome. Compare with the genome-wide p value. See Sections 11.3.4 and 12.5.2.


addition of typically 200 A residues to the 3′ end of a mRNA. The poly(A) tail is important for stabilizing mRNA. See Figure 1.18.

Polygenic character

a character determined by the combined action of a number of genetic loci. Mathematical polygenic theory (see Sections 19.2 and 19.3) assumes there are very many loci, each with a small effect.


strictly, the existence of two or more variants (alleles, phenotypes, sequence variants, chromosomal structure variants) at significant frequencies in the population. Looser usages among molecular geneticists include

any sequence variant present at a frequency >1% in a population,

any nonpathogenic sequence variant, regardless of frequency.


having multiple chromosome sets as a result of a genetic event that is abnormal (e.g., constitutional or mosaic triploidy, tetraploidy, etc.) or programmed (e.g. some plants and certain human body cells are naturally polyploid).

Primary transcript

the initial RNA product of transcription, before intronic sequences are spliced out. See Figure 1.14.


a short oligonucleotide, often 15–25 bases long, which base-pairs specifically to a target sequence to allow a polymerase to initiate synthesis of a complementary strand. Suitable primers are crucial for PCR, RT-PCR and DNA sequencing. See Figures 6.1 and 6.14.

Primer extension

a method of identifying the transcription initiation site. See Figure 20.2.

Primordial germ cells

cells in the fetus which give rise eventually to the sperm or egg cells.

Prior probability

in Bayesian statistics, the initially estimated probability of an outcome before all relevant information has been taken into account. See Box 17.2 and Figure 17.15.


a known DNA or RNA fragment (or a collection of different known fragments) which is used in a hybridization assay to identify closely related DNA or RNA sequences within a complex, poorly understood mixture of nucleic acids (the target). In standard hybridization assays, the probe is labeled (Figure 5.8), but in reverse hybridization assays the target is labeled (see Box 5.4).

Processed pseudogene (retropseudogene)

a pseudogene which lacks intronic sequences and flanking sequences of the related functional gene. Originates by reverse transcription. See Figure 7.13 and Box 7.3.


a unicellular organism, either a bacterium or an archaeon, where the cell has a simple internal structure. See Figure 2.1.


a combination of short sequence elements to which RNA polymerase binds in order to initiate transcription of a gene. See Figure 1.13.


an enzymic mechanism by which DNA replication errors are identified and corrected. See Figure 18.17.

Protein truncation test

a method of screening for chain-terminating mutations by artificially expressing a mutant allele in a coupled transcription–translation system. See Figure 17.9.


the complete protein repertoire of an organism (named by analogy to the genome, the complete gene repertoire).


any unicellular eukaryote. Can resemble an animal (protozoon), or a plant.


a cellular gene which can be converted by activating mutations into an oncogene. The term oncogene is now widely used for both the normal and activated forms of such genes. See Table 18.2.


a phage or viral genome that has integrated into the chromosomal DNA of a cell. See Figures 4.10 and 22.14.

Pseudoautosomal region

a region at the tips of the sex chromosomes marked by homology between the X and Y chromosomes which may be involved in recombination during male meiosis. See Figure 14.7.


a DNA sequence which shows a high degree of sequence homology to a nonallelic functional gene but which is itself nonfunctional. Different classes of pseudogene are described in Box 7.3.

Quantitative trait locus (QTL)

a locus important in determining the phenotype of a continuous character. Section 19.5.7 discusses the search for QTL underlying human obesity.

Radiation hybrid

in human physical mapping, a rodent cell that contains numerous small fragments of human chromosomes. Produced by fusion with a lethally irradiated human cell. Radiation hybrid panels allow very rapid mapping of STSs. See Figure 10.4.

Rare cutter

a restriction nuclease which cuts DNA infrequently because the sequence it recognizes is large and/or contains one or more CpGs. Examples are NotI, SacII and BssHII. See Table 4.1.

Reading frame

during translation, the way the continuous sequence of the mRNA is read as a series of triplet codons. There are three possible reading frames for any mRNA, and the correct reading frame is set by correct recognition of the AUG initiation codon.

Reassociation kinetics

The rates at which complementary DNA strands reassociate. Highly repetitive sequences reassociate rapidly; single copy sequences reassociate slowly. See Section 5.2.2.


a character is recessive if it is manifest only in the homozygote.


In linkage analysis, a person who inherits from a parent a combination of alleles that is the result of a crossover during meiosis. See Figure 11.1. Recombinant DNA is DNA containing covalently linked sequences with different origins, for example a vector with an insert.

Recombination fraction

for a given pair of loci, the proportion of meioses in which they are separated by recombination. Usually signified as q. q values vary between 0 and 0.5. See Section 11.1.

Renaturation (reannealing, reassociation)

reformation of double helices from complementary single strands. The basis of all hybridization assays.

Repetitive DNA

a DNA sequence that is present in many identical or similar copies in the genome. The copies can be tandemly repeated or dispersed. See Tables 7.11 and 7.12.

Replication fork

the point of bifurcation when a DNA double helix is being replicated. Two replication forks proceeding outwards from a single starting point create a replication bubble (Figure 1.10).

Replication slippage

a mistake in replication of a tandemly repeated DNA sequence, that results in the newly synthesized strand having extra or missing repeat units compared to the template. See Figure 9.5.

Reporter gene

a gene used to test the ability of an upstream sequence joined on to it to cause its expression. Putative cis-acting regulatory sequences can be coupled to a reporter gene and transfected into suitable cells to study their function. Alternatively, transgenic mice or other organisms can be made with a promotorless reporter gene integrated at random into its chromosomes, so that expression of the reporter indicates the presence of an efficient promoter (Figure 21.10).

Reporter molecule

a molecule whose presence is readily detected (for example, a fluorescent molecule) that is attached to a DNA sequence we wish to monitor. See, for example, Figure 5.7.

Response elements

sequence usually located a short distance upstream of promoters that makes gene expression responsive to some chemical in the cellular environment. Table 8.4 lists some examples.

Restriction fragment length polymorphism (RFLP)

a polymorphic difference in the size of allelic restriction fragments as a result of the polymorphic presence or absence of a particular restriction site. RFLPs can be assayed by Southern blotting (Figures 5.14 and 5.15) or PCR (Figure 6.6).

Restriction map

a diagram showing the positions of restriction sites within a DNA sequence. In short sequences these can be used as landmarks. See Figure 4.9.

Restriction site

a short DNA sequence, often 4–8 bp long and usually palindromic, which is recognized by a restriction endonuclease. See Table 4.1.

Retrotransposon (retroposon)

a transposable DNA element that transposes by means of an RNA intermediate. Retroposons encode a reverse transcriptase that acts on the RNA transcript to make a cDNA copy, which then integrates into chromosomal DNA at a different location. See Box 7.4 and Figures 7.17 and 7.18.


an RNA virus with a reverse transcriptase function, enabling the RNA genome to be copied into cDNA prior to integration into the chromosomes of a host cell. See Figures 18.2 and 18.3.

Reverse transcriptase

an enzyme that can make a DNA strand using an RNA template. Used to make cDNA libraries (Figure 4.8) and for RT-PCR (Section 20.2.4). Reverse transcription is an essential part of the retroviral life cycle (Figure 18.2) and is also encoded by some LINE-1 elements (Figure 7.18).


a labeled RNA probe prepared by in vitro transcription from a cloned DNA sequence. See Figure 5.4.


a natural or synthetic catalytic RNA molecule. See Figures 22.9 and 22.10.

RNA editing

a natural process in which specific changes occur post-transcriptionally in the base sequence of an RNA molecule. Occurs rarely in human genes. See Figure 8.16.

Robertsonian fusion

a chromosomal rearrangement that converts two acrocentric chromosomes into one metacentric. See Figure 2.21. Sometimes called centric fusion, although the point of exchange is actually in the proximal short arm, and not at the centromere.

RT-PCR (reverse transcriptase-PCR)

a PCR reaction that amplifies a cDNA made by reverse transcription of a mRNA. See Section 20.2.4.


this word has two different meanings in genetics

satellites on chromosomes are stalked projections variably present on the short arms of human acrocentric chromosomes (13, 14, 15, 21, 22).

satellite DNA originally described a DNA fraction that forms separate minor bands on density gradient centrifugation because of its unusual base composition. The DNA is composed of arrays of tandemly repeated DNA sequences. See Section 7.4.1 and Table 7.11.

Secondary structure

regions of a single-stranded nucleic acid or protein/polypeptide molecule where chemical bonding occurs between distantly spaced nucleotides or amino acids resulting in complex structures. Secondary structure is often due to intra-strand hydrogen bonding (Figures 1.7 and 1.24).

Segregation ratio

the proportion of offspring who inherit a given gene or character from a parent.


DNA replication is semiconservative because each daughter duplex contains one old and one newly synthesized strand (Figure 1.8).


describes a mutation which, in the heterozygote, produces a phenotype intermediate (but not necessarily halfway) between the wild type and the homozygote. A term widely used in mouse genetics, but better avoided, at least in human genetics, since dominance is a property of a character and not of an allele.

Sense strand

the DNA strand of a gene that is complementary in sequence to the template (antisense) strand, and identical to the transcribed RNA sequence (except that DNA contains T where RNA has U). Quoted gene sequences are always of the sense strand, in the 5′–3′ direction. See Figure 1.12.

Sequence homology

a measure of the similarity in the sequences of two nucleic acids or two polypeptides (see Figure 20.4B).

Sequence tagged site (STS)

any unique piece of DNA for which a specific PCR assay has been designed, so that any DNA sample can be easily tested for its presence or absence. See Box 10.3.

Sib-pair analysis

a form of linkage analysis in which markers are tested for linkage to a disease or phenotypic trait by measuring the extent to which affected sib pairs share marker haplotypes. See Figure 12.2.

Signal sequence (leader sequence)

a sequence of about 20 aminoacids at the N-terminus of a polypeptide that controls its destination within or outside the cell. See Section 1.5.4.


combination of short DNA sequence elements which suppress transcription of a gene. See Box 8.2.

Silent (synonymous) mutation

a mutation that changes a codon but does not alter the amino acid encoded. See Box 9.2. Such mutations may still have effects on mRNA splicing or stability.

SINE (short interspersed repetitive element)

a class of moderate to highly repetitive DNA sequence families, of which the best known in humans is the Alu repeat family (Figure 7.18). See Table 7.12.

Sister chromatid

two chromatids present within a single chromosome and joined by a centromere. Nonsister chromatids are present on different but homologous chromosomes.

Sister chromatid exchange (SCE)

a recombination event involving sister chromatids. Since sister chromatids are duplicates of each other, such exchanges should have no effect unless they are unequal. However, an increased frequency of SCEs is evidence of DNA damage.

Site-directed mutagenesis

production of a specific predetermined change in a DNA sequence. Can be done in vitro on cloned DNA (section 6.4) or in vivo by homologous recombination (Section 21.3).

Slipped strand mispairing (replication slippage)

a process in which the complementary strands of a double helix pair out of register at a tandemly repeated sequence. The resulting daughter DNA strands will have extra or missing repeat units. See Figure 9.5.

SNP (single nucleotide polymorphism)

any polymorphic variation at a single nucleotide. SNPs include RFLPs, but also other polymorphisms that do not alter any restriction site. Although less informative than microsatellites, SNPs are more amenable to large-scale automated scoring.


small nuclear RNAs, often part of the RNA splicing mechanism. See Section 1.4.1 and Table 7.4.

Somatic cell

any cell in the body except the gametes.

Somatic cell hybrid

an artificially constructed cell in which chromosomes have been stably introduced from cells of different species. See Figure 10.1.

Southern blot

transfer of DNA fragments from an electrophoretic gel to a nylon or nitrocellulose membrane (filter), in preparation for a hybridization assay. See Figure 5.12.

Splice acceptor site

the junction between the 3′ end of an intron and the start of the next exon. Consensus sequence y11nyagR (Y = pyrimidine, R = purine, upper case = exon). See Figure 1.15.

Splice donor site

the junction between the end of an exon and the start (5′ end) of the downstream intron. Consensus sequence AGgtragt (R = purine, upper case = exon). See Figure 1.15.


a ribonucleoprotein complex used in RNA splicing. See Figure 1.16.


normally RNA splicing, in which RNA sequences transcribed from introns are excised from a primary transcript and those transcribed from exons are spliced together in the same linear order as the exons (see Figure 1.14). Natural DNA splicing is a much rarer event but occurs in B and T lymphocytes (see Figure 8.27 and 8.28).

Splicing enhancer sequences

sequences that increase the probability that a nearby potential splice site will actually be used.


single stranded conformation polymorphism or analysis, a commonly used method for point mutation screening. See Figure 17.6.

Stem cell

a cell which can act as a precursor to differentiated cells but which retains the capacity for self-renewal. See Figure 2.5.

Sticky ends (cohesive termini)

short single-stranded projections from a double-stranded DNA molecule, typically formed by digestion with certain restriction enzymes. Molecules with complementary sticky ends can associate, and can then be covalently joined using DNA ligase to form recombinant DNA molecules. See Figures 4.3 and 4.4.


see Sequence tagged site.

STS content mapping

checking a series of clones for the presence or absence of particular sequence tagged sites. Used as a tool in assembling clone contigs (see, for example, Figure 10.19).

Suppressor tRNA

a mutant transfer RNA molecule with a nucleotide substitution in the anticocon. Shows an altered coding specificity and is able to translate a nonsense (or missense) codon. See Box 4.3.

Synonymous (silent) substitution

a substitution that replaces one codon with another that encodes the same amino acid. See Box 9.2.


loci are syntenic if on the same chromosome. Syntenic loci are not necessarily linked if they are sufficiently far apart on the chromosome they will not cosegregate more than by random chance.

Target DNA

itemplate DNA used in a PCR reaction; (ii) DNA to which a known probe DNA is designed to hybridize in a hybridization assay.


a specialized structure at the tips of chromosomes. It consists of an array of short tandem repeats, (TTAGGG)n in humans, which form a closed loop and protect the chromosome end.

Template strand

in transcription, the DNA strand that base-pairs with the nascent RNA transcript. See Figure 1.12.

Termination codon

a UAG (amber), UAA (ochre), or UGA (opal) codon in a mRNA (and by extension, in a gene) that signals the end of a polypeptide.

Tissue in situ hybridization

a form of molecular hybridization in which the target nucleic acid is RNA within cells of tissue sections immobilized on a microscope slide. See Figure 5.17.

Tissue-specific transcription factors

proteins that cause a gene to be expressed only in a certain tissue. See Table 8.2 for examples.


trans-acting factors (protein or maybe RNA) affect expression of all copies of a gene, whereas cisacting factors (normally DNA sequences) regulate only the DNA molecule of which they are part.


the synthesis of RNA on a DNA template by RNA polymerase. See Section 1.3.3.

Transcription unit

a stretch of DNA that is naturally transcribed in a single operation to produce a single primary transcript. In straightforward cases, a transcription unit is the same thing as a gene.


uptake of DNA by eukaryotic cells (includes the exact equivalent of transformation in bacteria, but that word has a different meaning for eukaryotic cells). Also uptake of plasmid DNA by bacterial cells. See Box 20.4.

Transformation (of a cell)

uptake by a competent cell of naked high molecular weight DNA from the environment.

Alteration of the growth properties of a normal cell as a step towards evolving into a tumor cell – see, for example, Figure 18.4.

Transgenic animal

an animal in which artificially introduced foreign DNA becomes stably incorporated into the germ line. This can be accomplished by pronuclear microinjection or, in the case of transgenic mice, by the use of embryonic stem cells. See Figures 21.1 and 21.2.


G-A (purine for purine) or C-T (pyrimidine for pyrimidine) nucleotide substitution.


transfer of chromosomal regions between nonhomologous chromosomes. See Figure 2.21.

Transmission disequilibrium test (TDT)

a statistical test of allelic association. See Box 12.1.


a mobile genetic element – see Figure 7.16.


a nucleotide substitution of purine for pyrimidine or vice versa. See Figure 9.1.


of a cell, having 3 copies of the genome; of an organism, being made of triploid cells.


having three copies of a particular chromosome, e.g. trisomy 21.

Tumor-suppressor (TS) genes

genes whose normal function is to inhibit or control cell division. Tumors always have inactivating mutations in TS genes. See Section 18.5.

Two-hit hypothesis

Knudson’s theory that hereditary cancers require two successive mutations to affect a single cell. See Figure 18.8.

Two-hybrid system

see Yeast two-hybrid system.

Unequal crossover (UEC)

recombination between nonallelic sequences on nonsister chromatids of homologous chromosomes. See Figure 9.7.

Unequal sister chromatid exchange (UESCE)

recombination between nonallelic sequences on sister chromatids of a single chromosome. See Figure 9.7.

Uniparental disomy

a cell or organism with normal chromosome numbers, but abnormal parental origin, in that both copies of one particular chromosome pair are derived from one parent. Depending on the chromosome involved, this may or may not be pathogenic. See Section 2.6.4 and Box 16.6.

Untranslated regions (5UTR, 3UTR)

regions at the 5′ end of mRNA before the AUG translation start codon, or at the 3′ end after the UAG, UAA or UGA stop codon. See Figure 1.19.


in the direction of the 5′ end when a gene sequence is written in the conventional way (showing the sense strand, in the 5′ to 3′ direction).

Variable expression

Variable extent and intensity of phenotypic signs among people with a given genotype. See for example, Figure 3.5C.

Variable number of tandem repeat (VNTR) polymorphism

microsatellites, minisatellites and megasatellites are arrays of tandemly repeated sequences that often vary between people in the number of repeat units. See Table 7.11. The term VNTR is often used to mean specifically minisatellites.


a nucleic acid that is able to replicate and maintain itself within a host cell and that can be used to confer similar properties on any sequence covalently linked to it.

Vectorette PCR

see Bubble-linker PCR.


see Variable number of tandem repeat polymorphisms.

Western blotting

a process in which proteins are size-fractionated in a polyacrylamide gel, then transferred to a nitrocellulose membrane for probing with an antibody. See Figure 20.9.

Whole-genome amplification

a PCR method using highly degenerate primers that can amplify a very large number of random sequences spread across the genome. Can be used to allow repeated testing of DNA from a single cell, for example in typing single sperm (Section 11.5.4).

X-inactivation (lyonization)

the inactivation of one of the two X chromosomes in the cells of female mammals by a specialized form of genetic imprinting. See Figure 2.6.

YAC transgenic

a transgenic mouse in which the transgene is a complete YAC, allowing studies of the regulatory effects of sequences surrounding the gene involved. See Section 21.2.4.

Yeast artificial chromosome (YAC)

a vector able to propagate inserts of a megabase or more in yeast cells. See Figure 4.16.

Yeast two-hybrid system

a yeast-based system for identifying and purifying proteins that bind to a protein of interest. See Figure 20.16.

Zinc finger

a polypeptide motif which is stabilized by binding a zinc atom and confers on proteins an ability to bind specifically to DNA sequences. Commonly found in transcription factors. See Figure 8.7.

Zoo blot

a Southern blot containing DNA samples from different species. See Figure 10.21.


the fertilized egg cell.

Copyright © 1999, Garland Science.
Bookshelf ID: NBK7584
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