A glossary of molecular genetics

As the mysteries of the human genome continue to unravel, we will hear more and more about molecular genetics. Australian Prescriber has already featured articles on gene therapy and genetic testing.

An expanding science brings new terminology. To assist readers' understanding of genetics, the Executive Editorial Board decided to update a glossary which first appeared in the `Drug and Therapeutics Bulletin'. The Executive Editorial Board thanks Professor Ron Trent of the Department of Molecular and Clinical Genetics at the Royal Prince Alfred Hospital in Sydney for revising the glossary.

Alleles - Alternative forms of a gene at a given locus.

Anti-oncogene see Tumour suppressor gene.

Antisense technology - Use of synthetic nucleotide sequences, complementary to specific DNA or RNA sequences, to block expression of a gene.

Carrier - An individual who has one faulty gene, which codes for a genetic disease, and one normal allele. Usually implies a carrier of a recessive disease (e.g. cystic fibrosis) who will remain unaffected throughout life.

Centimorgan (cM) - A measure of distance between two genes based on the frequency with which they are inherited together. 1 cM is equivalent to a 1% frequency of recombination and approximately to 1 megabase.

Chromosome mapping - The assigning of a gene or other DNA sequence to a particular position on a specific chromosome. See also Linkage map and Physical mapping.

Cloning - The isolation of a particular gene or DNA sequence, e.g. from a library. In recombinant technology, genes or DNA sequences are cloned by inserting them into a bacterium or other microorganism, which is then selected and propagated. See also Positional cloning.

Codon - A sequence of 3 bases that typically codes for a particular amino acid, e.g. the sequence ACT encodes threonine, GCA alanine. A `stop' codon, e.g. TAG, signals the end of a protein coding sequence.

Complementary DNA (cDNA) - Single-stranded DNA synthesised from a messenger RNA template: often used as a probe in chromosome mapping.

Conserved sequence - A DNA sequence that has remained virtually unchanged throughout evolution. This is usually taken to imply that the sequence has an important function.

Contigs - An arrangement of overlapping cloned DNA sequences representing a region of the genome.

Cosmid - A large plasmid used as a vector for cloning medium-length (about 40-50 kb) DNA sequences. See also Kilobase (kb).

CpG islands - Relatively small regions of hypomethylated cytosine nucleotide bases associated with guanine bases. Frequently found at the beginning of a gene.

DNA fingerprinting - A pattern of DNA sequences, e.g. tandem repeat sequences, unique to an individual. This DNA `profile', which can be detected in minute amounts of cells (e.g. in blood or semen), can be used in criminal cases and paternity suits to establish identity.

Endonuclease see Restriction endonuclease.

Exon - The segment of a gene which codes for a polypeptide. During splicing, the exons are separated from the gene's introns - non-coding regions between exons.

Gene amplification - An increase in the number of copies of a DNA sequence. Can be used to increase the amount of a DNA sample to facilitate its analysis. See also Polymerase chain reaction.

Gene expression - The process by which the information encoded by a gene is converted into a protein. In clinical genetics, the way in which a gene is expressed in a given individual.

Gene therapy - The use of genetic intervention to treat disease. Techniques (still mostly experimental) include treatment of a genetic defect by insertion of a normal gene (e.g. cystic fibrosis), blockade of expression of an abnormal gene (e.g. the BCL2 leukaemia gene) with antisense technology and the introduction of a gene for an enzyme that converts a pro-drug into a cytotoxic metabolite (e.g. thymidine kinase to convert 5-fluorocytosine to 5-fluorouracil). See also Retrovirus, Transduction.

Genetic code - The sequence of DNA nucleotides that determines the amino acid sequence of the translated protein. The genetic code is 'read' in triplets of bases called codons.

Genome - The complete set of genes of an organism and the intervening DNA sequences.

Genome project (usually described as the Human Genome Project) - An international research program aimed at mapping all the genes in a genome, e.g. of humans, mouse, plant, some microorganisms.

Genotype - The genetic constitution of an individual, usually at a particular locus. See also Phenotype.

Heterozygote - An individual who has two different alleles at the same locus. A heterozygote who has one dominant disease gene and one normal gene will be affected by the disease (as in Huntington disease); one who has a recessive disease gene and a normal gene will be a carrier (as in cystic fibrosis).

Homeotic genes - Genes which determine the shape of the body along the antero-posterior axis of the embryo. Related to this is the homeobox which is a particular DNA sequence in homeotic genes.

Homozygote - An individual who has two identical alleles at a locus. A person who is homozygous for a recessive disease gene (e.g. cystic fibrosis) will be affected by that disease.

Hybridisation - The joining of two complementary sequences of DNA (or DNA and RNA) by base pairing. See also Probe.

Informatics - The study of how to apply computer and statistical techniques to the management of information. Bioinformatics has been greatly accelerated by the Genome Project.

In-situ hybridisation - Use of a labelled probe to detect any complementary DNA or RNA sequence in a tissue section, cultured cell or cloned bacterial cell. See also Cloning.

Intron see Exon.

Kilobase (kb) - Unit of length of DNA equivalent to 1000 nucleotides.

Library - A collection of DNA clones representing either all expressed genes, a cDNA library, or a whole genome, a genomic library.

Linkage - The tendency for genes lying close together on the same chromosome to be inherited together: used to infer inheritance of linked genes. See also LOD score.

Linkage map - A map of the relative positions of gene loci on a chromosome deduced from the frequency with which they are inherited together. Distances measured in centimorgans.

LOD score - Statistical test to determine whether a set of linkage data are linked or unlinked. LOD is an abbreviation of 'log₁₀ of the odds'. A LOD score of +3 would suggest a 1000:1 chance that there is linkage between a disease trait and a DNA marker in a linkage study.

Megabase (Mb) - Unit of length of DNA equivalent to 1 million nucleotides. The shortest human chromosome (number 21) is about 50 Mb long, the longest (number 1) about 250 Mb.

Microsatellite - A type of DNA polymorphism which involves very small repeating units such as dinucleotides.

Multifactorial disorders - In contrast to monogenic disorders such as cystic fibrosis, multifactorial disorders arise from the interactions between genes and the environment. An example would be cancer.

Mutation - A change in DNA sequence, ranging from an alteration in a single base (e.g. sickle cell haemoglobin) to loss or gain of chromosomal material (e.g. the Philadelphia chromosome in chronic myeloid leukaemia).

Northern blotting - Technique for transferring RNA fragments, after separation by electrophoresis on a gel, on to membrane filters, where labelled probes can be applied to locate complementary RNA sequences. Southern blotting is an analogous technique, used to locate DNA rather than RNA.

Nucleotide - A subunit of DNA or RNA, consisting of a base, a sugar and a phosphate.

Oncogene - A gene whose product can cause cancer by stimulating abnormal cell growth and excessive proliferation. A mutant form of proto-oncogene. See also Mutation.

Phenotype - The physical or biochemical characteristics of an individual resulting from the interaction between its genotype and the environment.

Physical mapping - A linear map of the locations of genes on a chromosome as determined by physical detection of overlaps between cloned DNA fragments (contigs) rather than by linkage analysis. See also Cloning.

Plasmid - An autonomously replicating DNA element, separate from the chromosome. These units, which occur only in bacteria, can be used as vectors of small (up to about 10 kb) fragments of foreign DNA. See also Kilobase (kb).

Polymerase chain reaction (PCR) - A serial reaction involving the use of a heat-stable DNA polymerase to amplify a DNA sequence millions of times in a few hours.

Polymorphism - The existence, in a population, of two or more relatively common alleles at a genetic locus.

Positional cloning - The cloning of a gene on the basis of its chromosomal location rather than its functional properties. Also called reverse genetics.

Primer (oligonucleotide primer) - A short DNA sequence used to initiate the synthesis of DNA, as in a polymerase chain reaction.

Probe - A specific DNA sequence, radioactively or fluorescently labelled, used with hybridisation techniques to detect complementary sequences in a sample of genetic material. See also Complementary DNA.

Proto-oncogene - A gene that normally regulates cell growth and proliferation, but which when mutated can cause cancer. See also Mutation, Oncogene.

Recombinant technology - Procedures used to join DNA sequences from different sources. Therapeutic applications include insertion of human genes, e.g. for insulin or growth hormone, into bacterial cells, which multiply rapidly in culture and synthesise large amounts of the human protein in question.

Reporter gene - A gene whose product can be used as a genetic 'label'. For example, a gene for neomycin resistance incorporated into a plasmid before transfection allows the subsequent detection of successfully transfected cells.

Restriction endonuclease - An enzyme that cleaves DNA at a specific site.

Restriction fragment length polymorphism (RFLP) - Variations between individuals in DNA fragments that are recognised as cutting sites by specific restriction enzymes. Used as markers in chromosome mapping.

Retrovirus - RNA virus which utilises reverse transcriptase during its life cycle. Useful vector for inserting DNA into cells for gene therapy.

Reverse transcription - DNA synthesis from RNA templates, catalysed by the enzyme reverse transcriptase; the opposite of transcription. Occurs naturally in retroviruses. Reverse transcription is used to synthesise DNA for probes.

Southern blotting see Northern blotting.

Splicing - The removal of introns from messenger RNA and the joining together of adjacent exons.

Tandem repeat sequence - Multiple copies of a short DNA sequence lying in series along a chromosome; used in physical mapping and linkage mapping and also in DNA fingerprinting because each person's pattern of tandem repeats is likely to be unique.

Transcription - The synthesis of RNA from its corresponding DNA sequence.

Transduction - In reference to gene therapy, the transmission of genetic material from one cell to another by viral infection.

Transfection - The transfer of new genetic material into cells.

Transgenic - The presence of foreign DNA in the germ line.

Translation - The process by which information in the RNA genetic code is used to direct protein synthesis.

Tumour suppressor gene (anti-oncogene) - A gene that normally shows cell growth and proliferation. Mutations in tumour suppressor genes can allow uncontrolled cell division and so can lead to malignancies.

Vector - A DNA molecule, usually derived from a virus or bacterial plasmid, which acts as a vehicle to introduce foreign DNA into host cells for cloning and then to recover it.

Yeast artificial chromosome (YAC) - A vector constructed from the various DNA sequences needed for replication in yeast cells. It can be used to clone large (up to 400 kb) fragments of foreign DNA and is especially useful for chromosome mapping. See also Kilobase (kb).

Reprinted with permission, with some amendments^*, from Drug and Therapeutics Bulletin 1996;34:15-6.
* Additional information prepared by Professor Ron Trent, Department of Molecular and Clinical Genetics, Royal Prince Alfred Hospital, Sydney