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)