Reference Glossary of genetic terms

This is a fairly extensive glossary for reference throughout the whole course. If you feel any other terms should be added, please email p.a.farndon@bham.ac.uk



Alleles - Alternative forms of a gene at the same locus

Aneuploidy – A chromosome constitution with one or more chromosomes extra or missing from a full euploid set

Anticipation – 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

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

Autosome - Any chromosome other than the sex (X or Y) chromosomes

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


Carrier - A healthy person who is a heterozygote for a recessive trait. Also refers to a person with a balanced chromosomal translocation

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 chromosomes

Centromere – 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.

Chiasma – A visible crossover between paired homologous chromosomes in prophase I of meiosis

Chromatid – From the end of S phase of the cell cycle 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

Chromosome painting – Fluorescence labelling of a whole chromosome by a FISH procedure in which the probe is a cocktail of many different DNA sequences from a single chromosome

Chromosomes
– thread-like, darkly staining bodies within the nucleus, composed of DNA and chromatin which carry the genetic information.

Clone - All the cells derived from a single cell by repeated cell division and having the same genetic constitution

Coding sequence - Sequence of bases in DNA which specifies the structure of a protein

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

Consanguineous - Where two people are related by blood (i.e. share at least one common ancestor)

Constitutional – An abnormality or a mutation of a genotype that was present in the fertilised egg, and is therefore present in all cells of a person

Consultand - A person requesting genetic counselling

Contiguous gene syndrome
– A syndrome caused by deletion of a chromosomal area containing a set of genes, several or all of which contribute to the phenotype

Cytogenetics - The branch of genetics concerned with the physical structure and appearance of chromosomes

Diploid – Having two copies of each type of chromosome; the normal constitution of most human somatic cells

Dominant - A trait expressed in a heterozygote

Dynamic mutation – An unstable expanded repeat that changes size between parent and child

Dysmorphic - An alteration in the normal form or appearance

Empiric risk - Recurrence risk based on experience rather than calculation

Epigenetic – 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

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

Euploidy – The state of having one or more complete sets of chromosomes with none extra or missing (ie normal!); the opposite of aneuploidy

Exon – 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)

Expressivity - Variation in the severity of a genetic trait

Flanking markers - Markers on either side of a disease locus

FISH - fluorescence in situ hybridisation. In situ hybridisation using a fluorescently labelled DNA or RNA probe.
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 translation reading frame of a mRNA by adding or deleting a number of bases that is not a multiple of three

Gain of function mutation – A mutation that causes inappropriate expression or function of the gene product, rather than simply loss of function

Gamete - A germ cell (sperm or ovum)

Gene
- The unit of inheritance: a part of the DNA molecule which directs synthesis of a specific polypeptide

Gene dosage – The number of copies of a gene. Abnormal dosage of some genes (dosage-sensitive genes) can cause developmental abnormalities

Gene frequency
– The proportion of all alleles at a locus that are the allele in question. 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 tracking - Following a gene through a family by observing the inheritance of a marker which is being inherited alongside the gene

Genetic counselling - Process by which information on genetic disorders is given to a family

Genome – 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

Genotype - The genetic constitution of an individual

Gonadal mosaicism - Presence of a mutation in germline but not somatic cells, which results in transmission of a genetic disorder by a healthy person

Haploid – Describing a cell (typically a gamete) which has only a single copy of each chromosome

Hardy-Weinberg distribution – The simple relationship between gene frequencies and genotype frequencies that is found in a population under certain conditions

Hemizygous – 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

Heterochromatin – A chromosomal region that remains highly condensed throughout the cell cycle and shows little or no evidence of active gene expression

Heteroplasmy - the co-existence of wild-type and mutant mitochondrial DNA molecules within a cell, tissue or organism

Heterozygote - An individual with one normal and one mutant allele at a given locus on a pair of homologous chromosomes

Heterozygote advantage – The situation when somebody heterozygous for a mutation has a reproductive advantage over the normal homozygote. Heterozygote advantage is the reason why several severe recessive diseases remain common

Homologous - Matched (usually of a pair of chromosomes)

Homozygote - Person having two identical alleles at a particular locus on homologous chromosomes

Hybridisation - Process by which single strands of DNA (or RNA) with homologous sequences bind together

Imprinting – Determination of the expression of a gene by its parental origin

Inbreeding – 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

Intron - Noncoding DNA which separates neighbouring 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.

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

Karyotype - The classified chromosome complement of an individual or cell

Linkage – 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

Locus - The precise location of a gene on a chromosome

Locus heterogeneity – Determination of the same disease or phenotype by mutations at different loci. A major problem for linkage analysis

Manifesting heterozygote
– A female carrier of an X-linked recessive condition who shows some clinical symptoms, presumably because of skewed X-inactivation.

Marker - Biochemical or DNA polymorphism occurring close to a gene and used in gene tracking

Mendelian disorder - Inherited disorder due to a defect in a single gene

Metaphase – 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

Microsatellite – A small run (usually less than 0.1 kb) of tandem repeats of a very simple DNA sequence, usually 1-4 bp, for example (CA). The primary tool for genetic mapping during the 1990s

MIM number – The catalogue number for a gene or mendelian character, as listed in Victor McKusick’s Mendelian Inheritance in Man, available as a book and electronically

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

Missense mutation – A nucleotide substitution that results in an amino acid change

Mitochondria - organelles in a cell's cytoplasm chiefly responsible for "energy production"

Mitochondrial inheritance – transmission of a mitochondrial trait exclusively through female relatives

Modifier gene – a gene whose expression can influence a phenotype resulting from mutation at another locus

Monosomic - Having only one of the pair of genes, DNA segments or whole chro-mosomes from a pair of homologous chromosomes

Mosaic - Individual derived from a single fertilised egg, but where an error in cell division or a new mutation leads to cells of two or more different genotypes

Multifactorial - Inheritance due to multiple genes at different loci which summate and interact with environmental factors

Mutation - An alteration in the structure of DNA

Non-disjunction – Failure of chromosomes (sister chromatids in mitosis or meiosis II; paired homologues in meiosis I) to separate (disjoin) at anaphase. The major cause of numerical chromosome abnormalities

Nonpenetrance – 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 counselling

Nonsense mutation – A mutation that occurs within a codon and changes it to a stop codon

OMIM – 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

Oncogene – A gene involved in control of cell proliferation which, when overactive can help to transform a normal cell into a tumour cell. 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

Paracentric inversion – Inversion of a chromosomal segment that does not include the centromere

Penetrance - Probability that a disease genotype will result in an abnormal phenotype

Pericentric inversion
– Inversion of a chromosomal segment that includes the centromere

Phenotype - The observable characteristics of an individual

Point mutation – A mutation causing a small alteration in DNA sequence at a locus. The term is usually used to mean the substitution, insertion or deletion of just a single nucleotide in a given gene.

Polymorphism - Genetic characteristic with more than one common form in a population

Polyploid - 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)

Proband - The individual who draws medical attention to a family

Probe - A DNA (or RNA) fragment which has been labelled (usually with radio-activity) and used in a hybridisation assay to identify related DNA (or RNA) sequences

Promoter – A combination of short sequence elements to which RNA polymerase binds in order to initiate transcription of a gene

Pseudoautosomal region – A region at the tips of the sex chromosomes (X and Y) marked by homology between the X and Y chromosomes which may be involved in recombination during male meiosis

Pseudogene - A DNA sequence which shows a high degree of sequence homology to a nonallelic functional gene but which is itself nonfunctional.

Recessive - A trait expressed only in homozygotes

Recombination fraction – For a given pair of loci, the proportion of meioses in which they are separated by recombination. Usually signified as q (Greek letter theta). q values vary between 0 and 0.5

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

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 or PCR

Robertsonian translocation
– A chromosomal rearrangement that converts two acrocentric chromosomes into one metacentric. Sometimes called centric fusion, although the point of exchange is actually in the proximal short arm, and not at the centromere.

Segregation ratio – The proportion of offspring who inherit a given gene or character from a parent

Sex chromosomes
- the chromosomes responsible for sex determination (XX in women; XY in men)

Sex-linked - Inheritance of a gene carried on a sex chromosome

Single gene disorder - Disease whose inheritance is controlled by one pair of genes (one on each homologous chromosome)

Sister chromatid – Two chromatids present within a single chromosome and joined by a centromere. Nonsister chromatids are present on different but homologous chromosomes

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

Somatic cell - Any cell in the body except the gametes

Southern blot – Transfer of DNA fragments from an electrophoretic gel to a nylon or nitrocellulose membrane (filter), in preparation for a hybridisation assay

Telomere – A specialised 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

Trait - Any gene-determined characteristic

Transcription – The synthesis of RNA on a DNA template by RNA polymerase

Translocation - The transfer of chromosomal material between chromosomes

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

Trisomy - Three copies of a given chromosome per cell

Two hit hypothesis – Knudson’s theory that hereditary cancers require two successive mutations to affect a single cell

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

Variable expression – Variable extent and intensity of phenotypic signs among people with a given genotype

X-inactivation (lyonization) – The inactivation of one of the two X chromosomes in the cells of female mammals by a specialised form of genetic imprinting

X-linked – genes carried on the X chromosome

X-linked dominant – a trait caused by a gene on the X chromosome which is manifest in heterozygous females.

X-linked dominant lethal conditions – disorders caused by a gene on the X chromosome which are seen only in females and not seen in males as they are thought to be incompatible with survival of the early embryo in hemizygous males (eg incontinentia pigmenti).

X-linked recessive – a trait caused by a gene on the X chromosome expressed in hemizygous males and which is carried by females.


Zygote – The fertilised egg cell

(PF, 17.04.01)