Glossary of genetic terms

Authors
Benjamin A Raby, MD, MPH
Robert D Blank, MD, PhD
Section Editor
Anne Slavotinek, MBBS, PhD
Deputy Editor
Jennifer S Tirnauer, MD
Disclosures: Benjamin A Raby, MD, MPH Employment (spouse): Paraxel [hematology (CRO)]. Robert D Blank,
MD, PhDConsultant/Advisory Boards: Bristol-Myers-Squibb [obesity, metabolic bone disease (FGF21
analogue)]. Anne Slavotinek, MBBS, PhD Other Financial Interest: Oxford University Press [royalties for book on
growth charts]. Jennifer S Tirnauer, MDNothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
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All topics are updated as new evidence becomes available and our peer review process is
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Literature review current through: Aug 2015. | This topic last updated: Jul 22, 2015.
INTRODUCTION One of the greatest obstacles clinicians experience in reading about and
understanding genetics is the extensive use of technical language and jargon. It should be noted
that genetic terms are frequently used imprecisely in published clinical literature. The following is
a compilation of some of the most important technical terms.
A more extensive discussion of terms can be accessed in standard genetics reference texts [1]. In
addition, a guide for the conventions regarding the proper names of genes and alleles in humans
can be found atwww.genenames.org/guidelines.html.
Glossaries of epidemiological terms and terms that apply to systematic reviews and metaanalyses are presented separately in UpToDate. (See "Glossary of common biostatistical and
epidemiological terms" and"Systematic review and meta-analysis", section on 'Glossary of
terms'.)
GLOSSARY
Allele One of a series of alternative forms at a specific region of a chromosome. At the
DNA level, different alleles have different base sequences.
Allele frequency The proportion of chromosomes in a population harboring a specific
allele. "Minor allele frequency" typically refers to the less common variant at a biallelic locus
and is usually used to refer to the frequency of a single nucleotide polymorphism (SNP).
Allelic heterogeneity Common occurrence of multiple mutations in one gene that all
result in the same disease or syndrome. As an example, more than 1500 mutations in the
cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis.
Note that this term differs from genetic heterogeneity.
Aneuploidy The state of having an abnormal number of chromosomes. A euploid
human karyotype has 46 chromosomes (figure 1). Aneuploidy can affect the entire somatic
cell population, as in trisomy 21, or it can affect a subset of cells, as in a tumor.

Anticipation A phenomenon whereby the symptoms of a genetically-based condition

appear at an earlier age, or with greater severity, in successive generations. Expansion of
short tandem or trinucleotide repeats is a known molecular cause for specific diseases
(such as myotonic dystrophy, fragile X syndrome, Huntingtons chorea) that manifest
anticipation.
Association The non-random relationship between an allele and a phenotype in a
population. Genetic association between a marker allele and a phenotype can result either
because the allele is a direct causal variant, because the allele is in linkage disequilibrium
with a causal variant in close proximity, or due to stratification of the population. Genetic
association is a property of alleles. See also Genome-wide association study.
Autosome A chromosome other than X or Y. The human genome has 44 autosomes
(22 pairs) (figure 1).
Autosomal A gene is autosomal if it is located on an autosome (ie, not a sex
chromosome). A gene's inheritance pattern is also referred to as autosomal if the pattern
corresponds to that of known autosomal genes (ie, is not sex-linked).
Carrier An individual who is heterozygous for a risk or disease allele. The term is
typically used to describe heterozygotes for mutations that cause autosomal recessive or Xlinked recessive disease, but it is also used to describe heterozygotes for risk alleles of
complex traits with variable penetrance, regardless of inheritance type.
Carrier rate The frequency of carriers in a population.
Carrier testing Clinical method of genotyping at risk populations or family members to
identify individuals, usually asymptomatic, who have a gene mutation for an autosomal
recessive or X-linked disorder. One example is prenatal screening for Tay-Sachs mutations
in people of Ashkenazi Jewish ancestry.
Centromere A condensed chromosome region that mediates attachment of
chromosomes to the mitotic or meiotic spindle. The centromere also contains the
information that preserves the normal chromosome number.
Chromatid One of two replications or copies of a chromosome formed prior to cell
division and joined together at their centromeres. The centromere is the last portion of a
chromosome to replicate during cell division. Sister chromatids are a pair of chromatids
attached at the centromere.
Chromatin A complex structure of DNA, RNA, and protein that facilitates efficient
packaging of DNA in cells. The primary structure of chromatin is the nucleosome, consisting
of double-stranded DNA coiled around a core of histone proteins. Nucleosomes packed
tightly together form a bead-on-string configuration, which in turn assembles in hierarchical
looping structures to create densely-packaged chromatin. The regulation of gene
transcription is governed by the uncoiling of packed chromatin (heterochromatin) into
exposed DNA (euchromatin).
Clonal Arising from a single clone or cell. Examples include clonal selection of
lymphocytes during immune development and clonal origin of leukemia cells or other tumor
cells.
Cloning Production of a genetically identical copy. Can refer to a single gene or to an
entire organism.
Coding region Portion of a gene that encodes a protein.

Coding mutation or polymorphism See also Mutation. A genetic variation in the

open reading frame of a gene. Coding variants that alter amino acid composition of a protein
are called non-synonymous or missense variants (figure 2). Variants that do not alter amino
acid composition are called synonymous variants. Nonsense variants are coding variants
that result in the introduction of a stop codon (figure 3). A frame-shift mutation results from
an insertion or deletion of a number of bases not divisible by three, resulting in shifting of the
reading frame (figure 4).
Codon A three-nucleotide sequence that codes either for a specific amino acid or for
chain initiation or termination during protein synthesis.
Complementation The restoration of normal phenotype by gene replacement. The
replaced gene can either be an intact copy of a defective gene (direct replacement), or a
gene with function that can compensate for the defective gene's aberrant function.
Complex trait/complex disease Trait or disease for which interactions between more
than one geneand/or environmental factors also play a role in the phenotype.
Compound heterozygote An individual bearing two different pathogenic mutations in
the same gene that together are sufficient to manifest an autosomal recessive phenotype.
This differs from double heterozygote, which refers to an individual who is heterozygous for
mutations at two separate genetic loci, which together manifest disease.
Consanguinity The state of genetic relatedness between two individuals who produce
offspring. Consanguineous mating increases the probability of a rare recessive disease,
resulting from higher probability of both parents sharing a rare mutation.
Copy number variation The most prevalent type of chromosomal structural variation,
in which the number of copies of a large chromosomal or DNA segment (usually measuring
thousands to millions of bases) varies between individuals.
Crossing-over The exchange of chromosome segments that occurs between
homologous chromosomes during meiosis. Crossing over is the most common mechanism
of recombination. The site on the chromosome where the exchange occurs is called a
crossover.
Coupling The presence of two specified alleles at two linked loci on the same
homologous chromosome (ie, in cis), and the two alternative alleles on the other
chromosome. For illustration, in the case of dominant and recessive alleles, the coupling
gametes formed are AB and ab. In contrast, repulsion refers to the presence of the specified
alleles at two linked loci on different chromosomes (ie, in trans) (figure 5). In the example of
dominant and recessive alleles, repulsion gametes formed are Ab and aB.
De novo mutation A novel genetic sequence variant introduced by a germline
mutation. Often used to distinguish familial from sporadic cases of genetic disease.
Digenic inheritance Diseases caused by co-inheritance of mutations at two distinct
genetic loci (ie, in two different genes).
Diploid Possessing two copies of each autosomal chromosome and two sex
chromosomes. Most human cells are diploid. Gametes are haploid (one copy of each
autosome) (figure 1). Normal hepatocytes are tetraploid.
DNA barcoding A method for determining the species of origin of a DNA sample, using
molecular techniques such as PCR supplemented with bioinformatics data. A clinical
example is identification of the ingredients in an herbal preparation.

DNA barcoding can also refer to the addition of unique labels to DNA samples for
identification. As an example, this type of barcoding may be used to label DNA from different
individuals when next-generation sequencing is used.
Dominant negative Alleles that cause an abnormal phenotype or disease by a
mechanism that depends on the presence of an abnormal gene product interfering with the
function of the products from a normal gene.
Double heterozygote An individual who is heterozygous for two mutations at two
separate genetic loci that together are sufficient to manifest a phenotype. Differs from
compound heterozygote.
Embryonic stem cell A pluripotential cell derived from the inner cell mass of an earlystage embryo that is capable of differentiating into cells derived from all three germ layers.
Epigenetic change A modification of a chromosome that does not alter the nucleotide
base sequence, but alters the expression of a gene. Epigenetic changes may be stable in
an individual, but may be reversed during gametogenesis or early development. DNA
methylation and histone acetylation are common epigenetic changes. Epigenetic changes
form the mechanistic basis of imprinting.
Epistasis The process by which variations at two or more genetic loci interact to
produce phenotypes different from the individual effects of each variant. This process is
often referred to as either a gene-gene interaction or a genetic modifier effect.
Exome The portion of the genome that consists of exons.
Exome sequencing A sequencing strategy that provides the DNA sequence
corresponding to all exons (~1 percent of the genome), excluding introns and non-coding
genomic sequence. Though the complete exome includes non-coding 5 and 3 Untranslated
Regions (UTRs), most exome sequencing assays are enriched for the coding exons and
largely exclude the non-coding regions.
Exon A segment of DNA that is transcribed and present in mature messenger RNA
(mRNA). Many exons encode a portion of a protein, but non-coding exons also exist. This is
in contrast to an intron, the DNA sequence between exons that does not become part of
mature mRNA. Exons constitute only a small percent of the genome (about 1 to 2 percent).
Expressivity A parameter used in genetic models that quantifies the degree to which
an inherited characteristic is expressed in an organism.
Frameshift mutation A mutation that results from an insertion or deletion of a number
of bases that is not divisible by three, resulting in a shift of the reading frame (figure 4) and
thus altering the protein.
Fusion gene A functional gene product that results from the fusion of DNA segments
from two physically distinct genes. The fusion occurs as a consequence of chromosomal
rearrangements such as translocations, inversions, segmental deletions, or duplications.
Examples include the BCR-ABL and the FIP1L1-PDGFRA oncogenes.
Gene A unit of DNA sequence that encodes specific function. Classical definitions limit
genes to those elements that code for protein. However, non-protein coding genes (such as
non-coding RNAs or pseudogenes) are also genes.
Genetic heterogeneity Mutations in different genes resulting in the same phenotype or
disease. Examples include the multiple genetic causes of sensorineural deafness. This
differs from allelic heterogeneity.

Genetic polymorphism/genetic sequence variant An alternative DNA sequence or

chromosome copy number variant that can be found in a population.
Genotype The combination of two alleles at one genomic location or base pair in an
individual (applies to diploid organisms) (figure 5).
Genome editing Use of nucleases to insert or remove DNA from a genome. There are
several common technologies that make use of genome editing, including clustered
regularly interspaced short palindromic repeats (CRISPR), transcription activator-like
effector nucleases (TALENs) and zinc finger nucleases (ZFNs). CRISPR is increasingly
employed and is an RNA-guided gene-editing method that uses a bacterially-derived protein
(Cas9) and a specifically-designed synthetic guide RNA (gRNA) to introduce a doublestrand break at a precise location in the genome. The guide RNA directs the position of the
double-strand break by hybridization to its matching sequence. Genome editing can be used
in human cells and model organisms.
Genome-wide association study (GWAS) Pronounced gee-wass. A genetic mapping
study design that assesses for evidence of association between genetic variants and
heritable traits across the entire genome. Typical studies consist of genotyping hundreds of
thousands of common SNPs, using DNA microarrays or other methodologies in large casecontrol populations, with the goal of identifying specific risk alleles that are more prevalent in
cases than in controls.
Germline Referring to the gametic cell lines (ova and spermatozoa and their
precursors) that have the capacity to give rise to offspring.
Haploid Possessing one copy of each autosomal chromosome and one sex
chromosome, and therefore effectively one copy of each gene. Gametes (ova and sperm)
are haploid. Fertilization of a haploid ovum by a haploid sperm results in formation of a
diploid embryo. Many microorganisms are haploid.
Haploinsufficiency Refer to definition of Hemizygous below.
Haplotype The physical combination or sequence of alleles present on a single
chromosome. By definition, alleles on one haplotype are in cis (figure 5).
Hemizygous The state of carrying only one copy of a genomic region due to deletion of
the corresponding region on the other chromosome. Carriers of large-scale deletions are
hemizygotes. Hemizygosity can confer disease if having one normally functioning copy is
insufficient for normal cellular function (haploinsufficiency). Hemizygosity can also confer
disease if a pathogenic mutation is present within the hemizygous region.
Heritability The proportion of phenotypic variation that is explained by genetic factors.
Heteroplasmy The occurrence in a single cell of more than one different population of
mitochondrial DNA sequence.
Identity by descent Alleles are identical by descent if they can be traced back to a
common ancestor. Identity by descent is a more stringent classification than identity by
state. Identity by descent is the basis for establishing linkage.
Identity by state Alleles are identical by state if the assay being used to distinguish
alleles determines that they are identical. Identity by state is the basis for establishing
association.
Imprinting Gamete-specific gene silencing, in which only the allele from the mother or
only the allele from the father is expressed, leading to observed parent-of-origin effects in

offspring. Examples include the Prader-Willi syndrome and Angelman Syndrome locus and
a gene involved in pseudohyperparathyroidism. (See "Epidemiology and genetics of PraderWilli syndrome" and "Congenital cytogenetic abnormalities".)
Indel A class of common polymorphisms defined by an extra copy or a missing copy of
a short genetic or chromosomal sequence.
Induced pluripotent stem cell (iPSC) A pluripotent cell capable of differentiation to
mature lineages that is derived by in vitro reprogramming of a somatic cell.
Intron A segment of DNA between two exons that is transcribed to pre-mRNA but is
removed through the process of splicing and is therefore not part of mature mRNA.
Inversion A chromosomal rearrangement characterized by rotation and reintegration of
a DNA segment, resulting in an inverted orientation of the segment relative to its typical
state.
Linkage The relationship that exists between two loci that violate the Mendelian law of
independent assortment and therefore segregate in families in a non-random fashion. Nonindependent assortment results because linked loci reside together on the same
chromosome (ie, they are syntenic). However, most syntenic loci are not linked due to
mandatory recombination during meiosis. Linkage therefore implies the linked loci are in
close physical proximity to each other. The genetic linkage distance is expressed by
recombination fraction as expressed in centiMorgans (cM). Note that this is not necessarily
proportional to the physical distance (base pairs) separating the loci.
Linkage analysis Method of gene mapping that tests for the non-random segregation
of disease phenotypes with discrete chromosomal segments. Identification of linked regions
implies the existence of disease-causing mutations within or proximal to the linked region.
The process of disease-gene identification within this region is termed positional cloning.
Linkage disequilibrium The non-random association of alleles at two or more loci in a
population. Linkage disequilibrium is present when the observed haplotype distribution of
two or more markers in a population is significantly different from the expected haplotype
distribution (which can be derived from the cross-product of observed allele frequencies)
(figure 6).
Locus A specific chromosomal or genomic location. Plural = loci.
LOD score Logarithm of the odds score. A quantitative measure of the statistical
evidence of linkage between two genes. The LOD score depends on both the probability of
cosegregation of the two genes during meiosis and the size and structure of the population
in which the linkage analysis is performed. By convention, LOD scores >3 are considered to
be evidence of linkage in human studies. In some studies, the threshold LOD scores for
linkage can be established via permutation testing.
Lyonization See X-inactivation.
Manhattan plot A type of plot used to display results of a GWAS study. Genomic
coordinates are shown on the X-axis and the negative logarithm of the P-value for each
SNP on the Y-axis. SNPs with the strongest association will have the lowest P-values, and
hence the tallest profiles. Named for the appearance of the skyline in Manhattan in the
United States (figure 7).
Marker A locus with alternative alleles that can be used in genetic mapping
experiments.

Meiosis The cell division process in germline cells by which the chromosomal
complement is reduced from the diploid to the haploid number (figure 8).
Mendelian inheritance A trait is said to have Mendelian inheritance if its genetic
transmission can be explained by a Mendelian model of inheritance, such as autosomal
dominant, autosomal recessive, or X-linked recessive inheritance. This is in contrast to
digenic and quantitative traits.
Methylation The addition of methyl groups to cytosine in DNA. Methylation, when
followed by deamination, is a major pathway for mutation to thymine. Methylation also
correlates with reduced gene transcription and is an important mechanism for gene
imprinting and X-inactivation.
Micro-RNA (miR) A small, non-coding RNA that regulates the stability or translation of a
set of mRNAs.
Microsatellite A tandem array of short sequences of DNA (typically two to four bases).
Microsatellites are numerous and widely distributed in the genome. There is often
polymorphism in their length, making them useful markers in genetic studies, including
genome mapping and family-based linkage analysis. Microsatellites are also known as short
tandem repeat markers (STRs).
Mitochondrial genome The genetic material carried within mitochondria. At
fertilization, all the mitochondria are derived from the egg, so mitochondrial genes display
maternal inheritance.
Mitosis The process of cell division occurring in somatic cells, in which each daughter
cell receives a full chromosome complement.
Monogenic trait/monogenic disease Trait or disease with inheritance that can be
explained by a single gene, in contrast to polygenic and complex diseases.
Mutation, mutant An altered version of a gene. These terms are used in several
different senses, depending on context:
A genetic variant of low population frequency, in contrast to a polymorphism (often a
single nuclear polymorphism, or SNP) with an allele frequency of 1 percent or greater.
Types of gene mutations include nonsense (creates premature stop codon) (figure 3);
missense (creates amino acid change) (figure 2); silent (no associated change in
protein sequence); and frameshift (shifts the reading frame of the DNA and alters
protein translation, resulting in an entirely new protein sequence downstream of the
mutation) (figure 4).
Implication of abnormal function (eg, sickle cell mutation of the hemoglobin beta
chain).
Implication of recent sequence change (either germline or somatic), in contrast to
inheritance from a carrier parent.
An organism or population can harbor a specific mutation (eg, antibiotic-resistant
mutants).
Next-generation sequencing Any of several high-throughput DNA sequencing
methods that rely on parallel analysis of multiple DNA fragments (eg, whole genome
sequencing, exome sequencing). These methods have resulted in dramatic decreases in
the cost and time needed for sequencing projects and are used in some clinical settings.

Non-coding variant Genetic variation that does not map to gene regions that code for
protein. These variants can be functional if they reside in and disrupt functional elements,
such as non-coding RNA sequences or regulatory sites (eg, promoters, enhancers,
suppressors, or splice-sites).
Oncogene Gene that contributes to the production of cancer. Oncogenes typically act
in a dominant manner (ie, an oncogenic mutation at one allele is sufficient to promote
tumorigenesis).
Pedigree A diagram or other graphic representation of a family that shows the family
relationships, sex of each family member, and presence or absence of one or more
diseases in each individual (figure 9).
Penetrance The probability that an individual harboring a disease-causing mutation will
develop the associated disease or condition. Incomplete (or variable) penetrance occurs
when an individual with a disease-causing mutation does not manifest features of the
disorder. There are many causes of incomplete penetrance, including absence of
environmental or genetic co-factors, epigenetic effects such as imprinting, sex-specific
effects, or age-related expression differences.
Phenotype A characteristic of an organism (as opposed to the organisms genotype).
Phenotypes are sensitive to the assays used to assign or measure them. They may be
categorical, such as presence or absence of a disease; or quantitative, such as systolic
blood pressure. Further complexities in phenotypic description involve the physiological
state of the organism at the time of measurement, age, or use of provocative stimuli. Most
phenotypes are variable, and this variability leads to the concepts of penetrance and
expressivity.
Pleiotropy The association of variant(s) in a single gene with multiple phenotypic
effects, often in different tissues or organs. An example is Marfan syndrome, in which
mutations in the fibrillin 1 (FBN1) gene can cause cardiac, ocular, and connective tissue
findings.
Ploidy The number of sets of chromosomes present in an organism or cell. Ploidy
varies among different organisms, including those that are always haploid (eg, bacteria),
either haploid or diploid (eg, Saccharomyces species [yeast]), consistently diploid (eg,
mammals), or polyploid (eg, hexaploid wheat). Different tissues in multicellular organisms
may have different ploidies (eg, mammalian hepatocytes may be tetraploid). The
designation of ploidy is based on the predominant ploidy of cells in the organism.
Polymorphism A genetic region for which there are at least two different alleles present
in at least one population. Most commonly refers to a common single base-pair change or
single nucleotide polymorphism (SNP). By definition, a SNP has a population frequency of
at least 1 percent, in contrast to a mutation, which has a frequency of less than 1 percent.
A polymorphism also refers to any biologic marker (DNA, RNA, or protein) with two or more
states. Protein polymorphisms (varying amino acid sequence) can result from differences in
DNA sequence (ie, DNA polymorphisms) or from differential RNA splicing (ie, isoforms),
which in turn can result from sequence variation, epigenetic phenomenon,
or temporal/spatial/environmental differences.
Polygenic trait/polygenic disease In contrast to monogenic diseases, polygenic
diseases are those for which the inherited trait(s) is explained by more than one gene.

Polymerase chain reaction (PCR) A method of specifically amplifying a unique target

sequence (DNA or RNA) in the laboratory. PCR uses specific primers and repeated cycles
of heating and cooling with a heat-stable DNA polymerase to replicate the template material
exponentially.
Quantitative traits and quantitative trait loci (QTL) "Quantitative" traits are
distinguished from discrete traits. The population varies continuously for quantitative traits
and falls into obvious phenotypic classes for discrete traits. Quantitative traits are
sometimes referred to as "complex" traits, reflecting the fact that multiple genes, the
environment, and gene-environment interactions all contribute to an individual's trait value.
Many traits are quantitative, and their inheritance is much more challenging to unravel than
discrete traits. A quantitative trait locus (QTL) is a genomic region linked or associated with
a quantitative trait.
Read depth In genomic or gene sequencing, the number of independent times each
base in a targeted region has been sequenced. Typically expressed as an average X
coverage (for example 20X = an average of 20 sequence reads per base). A minimum read
depth of 30X is often required for clinical-grade sequencing. See Next-generation
sequencing.
Reading frame The starting point in translating the DNA sequence to protein. Since
each codon includes three nucleotides, the reading frame can be initiated at one of three
nucleotides. Offsetting the reading frame changes the amino acid composition of the
encoded protein.
Recombinant Refers to offspring whose genotype and phenotype combinations differ
from their parents, implying genetic recombination between the loci under study.
Recombinant technologies, or genetic engineering, are molecular genetic approaches that
use the process of homologous recombination to manipulate genotypes for experimental
purposes.
Examples include transgenic models where specific genetic loci are either knocked-out
(removed) or knocked-in (introduced) to enable study of the locus; recombinant inbred
mouse strains; recombinant viral transfection for synthesis of protein.
Recombination The process of exchanging DNA sequence between two homologous
chromosome regions. Mandatory recombination occurs at least once per aligned
chromosome pair during meiosis. The exchange results in the creation of novel haplotypes
that are combinations of the grandparental haplotypes present in a diploid cell. Exchange of
unequal sequence content (ie, non-homologous recombination) can introduce DNA gains
and losses of thousands or millions of bases. These gains and losses result in structural
genetic variation and copy number variants (CNVs).
Repulsion The state in which alleles at two distinct loci are on physically opposing
chromosomal strands. By definition, these variants are not part of the same haplotype
(figure 5). The opposite relationship is coupling.
Risk allele An allele associated with a disease phenotype. Though a risk allele is often
that which is least common (ie, the minor allele), risk alleles associated with some complex
traits may be the more common allele.

RNA interference (RNAi) A ubiquitous intracellular process mediated by small RNA

species, whereby specific RNAs are targeted for editing, degradation, or clearance. RNA
interference has important roles in the regulation of gene expression, developmental
processes, cellular defense, and epigenetic effects.
RNAi technology has been used in the laboratory to test the function of a gene by
preventing its expression. Its use has been attempted clinically as a means of
posttranscriptional gene silencing to reduce the expression of viral or cancer genes, or to
lower cholesterol.
Sequencing Determination of the nucleotide base sequence of a gene or collection of
genes; see also exome sequencing and whole genome sequencing and next-generation
sequencing.
Silencing Regulation that prevents the expression of a gene. Mechanisms of silencing
include gene methylation, destruction of messenger RNA, or prevention of protein
translation.
Single nucleotide polymorphism (SNP) Pronounced snip. A polymorphism that
affects a single base pair with a population frequency of at least one percent. Single base
pair changes that occur at a lower population frequency are, by convention, called mutations
if they affect protein function. Refer to definition of Polymorphism above.
Somatic Refers to tissues that are not within the germline. Somatic mutations arise in
the somatic tissues and are therefore not passed from parent to offspring. Somatic
mutations are common in neoplasms.
Structural genetic variation A term that encompasses a variety of large-scale genomic
aberrations, including segmental rearrangements, translocations, or inversions and DNA
copy-number variants (CNVs). Large rearrangements or deletions can be visualized through
karyotyping. Smaller variants, particularly CNVs, segmental duplications, and
interchromosomal interstitial rearrangements, are assessed by array comparative genomic
hybridization (array CGH).
Syntenic Describing genetic loci that reside on the same chromosome. As an example,
the genes causing Birt-Hogg-Dub syndrome (Folliculin - FLCN, at chromosome 17p11) and
early-onset breast cancer (BRCA1, at chromosome 17q21) are syntenic to each other on
chromosome 17. However, because they sit far apart from each other, they are not linked.
Telomere Region at the ends of a chromosome that prevents the loss of genetic
material or the accidental fusion of two chromosomes together during cell division.
Telomeres of chromosomes in most cells shorten as an individual ages.
Telomerase Enzyme that extends the length of telomeres. Telomerase mutations are
seen in some inherited "telomere syndromes."
Translocation A structural chromosomal abnormality whereby chromosome segments
are swapped between two non-homologous chromosomes. This form of rearrangement can
be balanced, when the translocation does not result in any significant loss or gain of genetic
material in the resultant gamete; or unbalanced, when there is a gain or loss of genetic
material in the resultant gamete.

Tumor suppressor gene Gene that protects against the development or growth of
tumors. Tumor suppressor genes typically act in a recessive manner (ie, both normal copies
must be lost for a tumor to develop).
Uniparental disomy The inheritance of two copies of a chromosome (or part of a
chromosome) from one parent, and no copy from the other parent, due either to nondisjunction errors during either the first or second phases of meiosis, or to chromosomal
alterations in early fetal development. Non-disjunction during the first phase of meiosis
(meiosis I) will result in inheritance of each of the grandparental chromosomes from one
parent, termed heterodisomy. In contrast, non-disjunction during meiosis II results in
inheritance of two identical copies of one grandparental chromosome, termed isodisomy.
Variant See genetic polymorphism/genetic variant.
Variant of unknown significance (VUS) A classification term used in clinical DNA
sequencing reports to signify genetic polymorphisms for which the pathogenicity (likelihood
of causing disease) cannot be determined easily. VUS are variants that cannot be readily
classified as pathogenic, likely pathogenic, or benign.
Whole genome sequencing A sequencing strategy that provides the DNA sequence
for the entire genome, including exons, introns, and other non-coding sequence. In contrast,
exome sequencing only determines the sequence of gene coding regions.

1.

X-inactivation An epigenetic process that occurs in all female mammalian cells

whereby one of the two X chromosomes are randomly rendered inactive, such that all
subsequent gene expression is derived from the other (active) X chromosome. This is
sometimes called Lyonization, after Mary Lyon, who did important early work on this
phenomenon.
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REFERENCES
Brenner's Encyclopedia of Genetics, 2nd ed, Maloy S, Hughes K. (Eds), Elsevier, 2013.
Topic 2898 Version 21.0