NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.

Cover of GeneReviews®

GeneReviews® [Internet].

Show details

Illustrated Glossary

Terms and Definitions

A · B · C · D · E · F · G · H · I · K · L · M · N · O · P · Q · R · S · T · U · V · W · X · Z

A

affected

Referring to an individual who manifests symptoms of a particular condition

allele

One version of a gene at a given location (locus) along a chromosome

Related Terms: allele frequency; allelic variant of unknown significance; compound heterozygote; heterozygote; homozygote; locus; mutation; polymorphism; wild-type allele

Image LearnMore.jpg

allele frequency

Synonym: gene frequency

The proportion of individuals in a population who have inherited a specific gene mutation or variant

allele-specific oligonucleotide testing

Synonyms: ASO testing, ASO

The detection of a specific mutation using a synthetic segment of DNA approximately 20 base pairs in length (an oligonucleotide) that binds to and hence identifies the complementary sequence in a DNA sample

allelic heterogeneity

Synonym: molecular heterogeneity

Different mutations in the same gene at the same chromosomal locus that cause a single phenotype

Related Terms: allele; locus heterogeneity; mutation

Image LearnMore.jpg Image CaseExample.jpg

allelic variant of unknown significance

An alteration in the normal sequence of a gene, the significance of which is unclear until further study of the genotype and corresponding phenotype in a sufficiently large population; complete gene sequencing often identifies numerous (sometimes hundreds) allelic variants for a given gene

Related Terms: allele; benign variant; disease-causing mutation; mutation; polymorphism; sequence alteration

Image LearnMore.jpg Image CaseExample.jpg

alternate paternity

Synonyms: false paternity, nonpaternity

The situation in which the alleged father of a particular individual is not the biological father

Analysis of the entire coding region: Mutation scanning

Synonyms: scanning, mutation screening, mutation scanning

A 2-step process by which the entire coding region of a gene is first analyzed via one of a variety of methods (such as CSGE, DGGE, SSCP, DHPLC or TGCE) to identify sequence alterations. These methods do not identify the specific nucleotide change(s) and must be followed by further analysis (usually sequencing) to identify the specific sequence alteration

Related Terms: Analysis of the entire coding region: Sequence analysis; CSGE; DGGE; DNA-based testing; molecular genetic testing; PCR; SSCP; Targeted mutation analysis

Image LearnMore.jpg

Analysis of the entire coding region: Sequence analysis

Synonyms: sequence analysis, gene sequencing, sequencing

The process by which the nucleotide sequence is determined for the entire coding region of a gene

Related Terms: Analysis of the entire coding region: Mutation scanning; direct DNA analysis; DNA-based testing; molecular genetic testing; PCR; Targeted mutation analysis

Image LearnMore.jpg

analyte

A complex biological component of an enzymatic reaction; a substance that is typically measured in a Biochemical/Metabolic specialty laboratory that is absent, reduced in quantity, or increased in quantity, as a result of an abnormality in a metabolic pathway

aneuploidy

The occurrence of one or more extra or missing chromosomes leading to an unbalanced chromosome complement, or, any chromosome number that is not an exact multiple of the haploid number

anticipation

The tendency in certain genetic disorders for individuals in successive generations to present at an earlier age and/or with more severe manifestations; often observed in disorders resulting from the expression of a trinucleotide repeat mutation that tends to increase in size and have a more significant effect when passed from one generation to the next

Related Terms: intrafamilial variability; mutable normal allele; trinucleotide repeat; trinucleotide repeat testing; variable expressivity

Image LearnMore.jpg Image CaseExample.jpg

array comparative genomic hybridization

Synonyms: array CGH, aCGH, comparative genomic hybridization

One method of chromosomal microarray (CMA) used to detect copy number variations (losses or gains of chromosomal material), which may be benign, pathologic, or of unknown clinical significance. A far more sensitive method than traditional karyotyping, array CGH detects both large and small copy number variations. Depending on the method used, array CGH may detect copy number variations across the whole genome, or in a specific chromosome, chromosome segment, or gene.

Related Terms: chromosomal microarray (CMA)

Ashkenazi Jewish

Synonym: Eastern European Jewish

The Eastern European Jewish population primarily from Germany, Poland, and Russia, as opposed to the Sephardic Jewish population primarily from Spain, parts of France, Italy, and North Africa

autosomal

Refers to any of the chromosomes other than the sex-determining chromosomes (i.e., the X and Y) or the genes on these chromosomes

autosomal dominant

Describes a trait or disorder in which the phenotype is expressed in those who have inherited only one copy of a particular gene mutation (heterozygotes); specifically refers to a gene on one of the 22 pairs of autosomes (non-sex chromosomes)

Related Terms: de novo mutation; germline mosaicism; heterozygote; mode of inheritance; penetrance; variable expressivity

Image LearnMore.jpg Image CaseExample.jpg

autosomal recessive

Describes a trait or disorder requiring the presence of two copies of a gene mutation at a particular locus in order to express observable phenotype; specifically refers to genes on one of the 22 pairs of autosomes (non-sex chromosomes)

Related Terms: allele frequency; carrier; carrier testing; compound heterozygote; consanguinity; heterozygote; homozygote; mode of inheritance

Image LearnMore.jpg Image CaseExample.jpg

B

background risk

Synonym: population risk

The proportion of individuals in a given population who are affected with a particular disorder or who have mutations in a certain gene; often discussed in the genetic counseling process as a comparison to the patient's personal risk given his/her family history or other circumstances

Related Terms: allele frequency; carrier rate; risk assessment; risk assessment modification

Image LearnMore.jpg Image CaseExample.jpg

band

When chromosomes at a particular stage in cell division are stained using one of several types of preparations, a specific pattern of light and dark stripes (bands) appear which can aid in identifying the chromosome and evaluating its structure

band level

The total number of bands estimated to be present in a haplotype set (23) of chromosomes. When cell division is arrested and staining is performed at an earlier stage of mitosis (prometaphase), chromosomes appear longer, with approximately 700-1200 bands. At a later stage of mitosis (metaphase), chromosomes are more condensed, with approximately 300-600 bands. At higher band levels, the greater resolution increases the ability to identify more subtle chromosomal abnormalities and their breakpoints.

Related Terms: chromosome; high-resolution chromosome studies; karyotype

Image LearnMore.jpg Image CaseExample.jpg

base pair

Synonym: bp

Two nitrogenous bases paired together in double-stranded DNA by weak bonds; specific pairing of these bases (adenine with thymine and guanine with cytosine) facilitates accurate DNA replication; when quantified (e.g., 8 bp), refers to the physical length of a sequence of nucleotides

Related Terms: codon; nucleotide; reading frame

Image DiseaseExample.jpg Image LearnMore.jpg

benign variant

Synonym: polymorphism

An alteration in a gene distinct from the normal, wild-type allele that does not appear to have a deleterious effect

Related Terms: allelic variant of unknown significance

C

carrier

An individual who has a recessive, disease-causing gene mutation at a particular locus on one chromosome of a pair and a normal allele at that locus on the other chromosome; may also refer to an individual with a balanced chromosome rearrangement

Related Terms: autosomal recessive; carrier rate; carrier testing; compound heterozygote; double heterozygote; heterozygote; obligate carrier; obligate heterozygote; X-linked recessive

Image LearnMore.jpg Image CaseExample.jpg

carrier rate

Synonym: carrier freqency

The proportion of individuals in a population who have a single copy of a specific recessive gene mutation

Related Terms: allele frequency; carrier; heterozygote

Image LearnMore.jpg Image CaseExample.jpg

carrier testing

Synonyms: carrier detection, heterozygote testing

Testing used to identify usually asymptomatic individuals who have a gene mutation for an autosomal recessive or X-linked disorder

Related Terms: autosomal recessive; carrier; heterozygote; homozygote; molecular genetic testing; mutation; X-linked dominant; X-linked recessive

Image LearnMore.jpg Image CaseExample.jpg

centimorgan

The unit of linkage that refers to the distance between two gene loci determined by the frequency with which recombination occurs between them. Two loci are said to be one centimorgan apart if recombination is observed between them in 1% of meioses.

chromosomal microarray

Synonym: CMA

Refers to methods used to detect copy number variations (losses or gains of chromosomal material), which may be benign, pathologic, or of unknown clinical significance. A far more sensitive method than traditional karyotyping, CMA detects both large and small copy number variations. Depending on the method used, CMA may involve scanning of the whole genome, or of a specific chromosome or chromosome segment. The CMA methods used most commonly in clinical practice include oligo (oligonucleotide) array, SNP (single nucleotide polymorphism) array, and oligo/SNP combination array.

Related Terms: array comparative genomic hybridization (array CGH, aCGH), comparative genomic hybridization

chromosome

Physical structure consisting of a large DNA molecule organized into genes and supported by proteins called chromatin

Related Terms: aneuploidy; autosomal; cytogenetics; derivative chromosome; homologous chromosomes; karyotype; polyploidy

Image LearnMore.jpg

chromosome breakage studies

Cytogenetic testing to detect an increased rate of chromosomal breakage or rearrangement in metaphase cells by exposing cell cultures to clastogenic agents such as diepoxybutane (DEB) or mitomycin C (MMC); cell cultures not exposed to the DNA clastogenic agent are used as controls to measure the spontaneous rate of chromosomal breakage or rearrangement.

cis configuration

Synonyms: cis, coupling

Term which indicates that an individual who is heterozygous at two neighboring loci has the two mutations in question on the same chromosome

Related Terms: double heterozygote; pseudogene; variable expressivity

Image DiseaseExample.jpg Image LearnMore.jpg

clone

An identical copy of a DNA sequence or entire gene; one or more cells derived from and identical to a single ancestor cell; to isolate a gene or specific sequence of DNA

coding region

Synonym: open reading frame

All exons of a gene that contribute to the protein product(s) of the gene

Related Terms: codon; exon; intron; promoter region; reading frame

Image LearnMore.jpg

codon

In DNA or RNA, a sequence of three nucleotides that codes for a certain amino acid or signals the termination of translation (stop or termination codon)

comparative genomic hybridization

See array comparative genomic hybridization.

Related Terms: chromosomal microarray (CMA)

compound heterozygote

An individual who has two different abnormal alleles at a particular locus, one on each chromosome of a pair; usually refers to individuals affected with an autosomal recessive disorder

Related Terms: autosomal recessive; carrier; double heterozygote; heterozygote; homozygote

Image LearnMore.jpg Image CaseExample.jpg

conformation-sensitive gel electrophoresis

Synonym: CSGE

A type of mutation scanning in which a segment of DNA is screened for mismatch pairing between normal and mutated base pairs.

Related Terms: Analysis of the entire coding region: Mutation scanning; Analysis of the entire coding region: Sequence analysis; denaturing gradient gel electrophoresis; DNA-based testing; molecular genetic testing; polymerase chain reaction (PCR); single-stranded conformational polymorphism; Targeted mutation analysis

Image LearnMore.jpg

congenital

Present from birth, but not necessarily genetic

consanguinity

Genetic relatedness between individuals descended from at least one common ancestor

Related Terms: autosomal recessive; family history; pedigree

Image LearnMore.jpg Image CaseExample.jpg

consultand

The individual (not necessarily affected) who presents for genetic counseling and through whom a family with an inherited disorder comes to medical attention

contiguous gene syndrome

A constellation of findings caused by a small chromosome deletion or duplication that spans two or more adjacent genes

Related Terms: deletion; duplication; FISH; high-resolution chromosome studies; microdeletion syndrome

Image LearnMore.jpg Image CaseExample.jpg

cosegregation

The inclusion of two or more linked genes on a chromosome in the same gamete leading to their transmission together

Related Terms: crossing over; flanking marker; homologous chromosomes; intragenic marker; linkage analysis; marker; recombination

Image LearnMore.jpg Image CaseExample.jpg

critical region

The specific portion of a chromosome or a gene that, when altered in some way (deleted, duplicated, or otherwise mutated), produces the characteristic set of phenotypic abnormalities associated with a particular syndrome or disorder

crossing over

Synonym: recombination

The exchange of a segment of DNA between two homologous chromosomes during meiosis leading to a novel combination of genetic material in the gamete

Related Terms: cosegregation; linkage analysis; marker

Image LearnMore.jpg Image CaseExample.jpg

cryptic chromosome translocation

A chromosome translocation or rearrangement detected by special techniques (e.g., fluorescent in situ hybridization [FISH], telomeric detection) because it is too small to be seen with conventional cytogenetic techniques

CSGE

Synonym: conformation-sensitive gel electrophoresis

A type of mutation scanning in which a segment of DNA is screened for mismatch pairing between normal and mutated base pairs.

Related Terms: Analysis of the entire coding region: Mutation scanning; Analysis of the entire coding region: Sequence analysis; denaturing gradient gel electrophoresis; DNA-based testing; molecular genetic testing; polymerase chain reaction (PCR); single-stranded conformational polymorphism; Targeted mutation analysis

Image LearnMore.jpg

custom mutation analysis

Molecular genetic testing for a given specific mutation developed on an as-needed basis in a clinical laboratory for diseases for which testing is not otherwise clinically available. Situations in which custom mutation analysis may be used include: a) testing for at-risk family members when a disease-causing mutation has been identified in an affected family member in a research laboratory; b) prenatal testing for families in which a disease-causing mutation has been identified in an affected family member by a laboratory not offering prenatal testing.

custom prenatal testing

Prenatal testing offered to families in which disease-causing mutations have been identified in an affected family member in either a research or clinical laboratory; testing is not otherwise clinically available for prenatal diagnosis.

cytogenetics

The study of the structure, function, and abnormalities of human chromosomes

D

de novo mutation

Synonyms: de novo gene mutation, new gene mutation, new mutation

An alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell (egg or sperm) of one of the parents or in the fertilized egg itself

Related Terms: autosomal dominant; germline mosaicism; germline mutation; sporadic

Image LearnMore.jpg Image CaseExample.jpg

deletion

Absence of a segment of DNA; may be as small as a single base or as large as one or more genes

Related Terms: band; chromosome; contiguous gene syndrome; critical region; disease-causing mutation; DNA-based testing; FISH; high-resolution chromosome studies; karyotype; microdeletion syndrome

Image LearnMore.jpg Image CaseExample.jpg

deletion/duplication analysis

Synonym: copy number analysis

Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.

Related Terms: chromosomal microarray (CMA); PCR;

denaturing gradient gel electrophoresis

Synonym: DGGE

Identification of mutations by electrophoresis of double-stranded DNA samples through a denaturing gradient, such as urea. Certain mutations affect the migration pattern by changing the point in the gel at which the DNA denatures; mutant sequences can be distinguished from wild-type sequences by comparing the electrophoretic pattern.

densitometry

Method of identifying gene dosage or expression by measurement of light absorption on an autoradiogram (film) of a band (or spot) representing a DNA, RNA, or protein sample; useful in detecting duplication mutations and heterozygous deletion mutations

derivative chromosome

Term used to denote an abnormal chromosome consisting of segments from two or more chromosomes joined together as the result of a translocation, insertion, or other rearrangement

DGGE

Synonym: denaturing gradient gel electrophoresis

Identification of mutations by electrophoresis of double-stranded DNA samples through a denaturing gradient, such as urea. Certain mutations affect the migration pattern by changing the point in the gel at which the DNA denatures; mutant sequences can be distinguished from wild-type sequences by comparing the electrophoretic pattern.

diagnostic testing

Testing designed to confirm or exclude a known or suspected genetic disorder in a symptomatic individual or, prenatally, in a fetus at risk for a certain genetic condition

Related Terms: direct DNA analysis; DNA-based testing; karyotype; linkage analysis; molecular genetic testing; predictive testing; prenatal diagnosis

Image LearnMore.jpg Image CaseExample.jpg

diploid

The normal number of chromosomes in a somatic cell; in humans, 46 chromosomes (22 pairs of autosomes and two sex chromosomes)

direct DNA analysis

Synonym: direct DNA

The use of any test method, such as sequence analysis, mutation scanning, or mutation analysis to detect a mutation in a gene

Related Terms: Analysis of the entire coding region: Mutation scanning; Analysis of the entire coding region: Sequence analysis; linkage analysis; Targeted mutation analysis

Image LearnMore.jpg

disease-causing mutation

A gene alteration that causes or predisposes an individual to a specific disease

DNA

Synonym: deoxyribonucleic acid

The molecule which encodes the genes responsible for the structure and function of an organism and allows for transmission of genetic information from one generation to the next

DNA banking

The process through which DNA is extracted from any of a number of possible cell sources and stored indefinitely by freezing or refrigerating for future testing; done when a specific test is not presently available or when the decision to have testing has not been made

Related Terms: DNA-based testing; informed consent; molecular genetic testing

Image LearnMore.jpg Image CaseExample.jpg

DNA-based testing

Synonyms: molecular genetic testing, DNA testing

Testing that involves the analysis of DNA, either through linkage analysis, sequencing, or one of several methods of mutation detection

domain

A specific region or amino acid sequence in a protein associated with a particular function or corresponding segment of DNA

dominant

See autosomal dominant or X-linked dominant.

dominant negative mutation

A mutation whose gene product adversely affects the normal, wild-type gene product within the same cell, usually by dimerizing (combining) with it. In cases of polymeric molecules, such as collagen, dominant negative mutations are often more deleterious than mutations causing the production of no gene product (null mutations or null alleles).

dosage analysis

Method of measuring the quantity of a variety of analytes, including DNA, RNA, and protein, by comparison with a known standard; can be used to determine the number of copies of a sequence of DNA (i.e., to test for duplication and deletion mutations) either by visual comparison of band intensity or numerical quantification by densitometry. If extra copies of a gene are present, intensity is greater than 100% on a gel or film; whereas, if one copy of the gene is missing, the intensity is approximately 50%.

double heterozygote

An individual who is heterozygous for a mutation at each of two separate genetic loci

Related Terms: carrier; cis configuration; heterozygote; homozygote; locus; trans configuration

Image LearnMore.jpg Image CaseExample.jpg

duplication

The presence of an extra segment of DNA, resulting in redundant copies of a portion of a gene, an entire gene, or a series of genes, usually caused by unequal crossing-over during gene replication when gametes are formed in meiosis

dysmorphology

The clinical study of malformation syndromes

E

enzyme assay

Measurement of enzyme activity with a particular substrate; can be assessed in a variety of ways including quantification of the end product or colorimetric analysis

euploid

Any chromosome number that is a multiple of the haploid number

exon

Coding sequence of DNA present in mature messenger RNA

Related Terms: coding region; intron; open reading frame

Image LearnMore.jpg

exon scanning

The process by which certain exons (coding regions within a gene), under highest suspicion to contain a specific mutation, are subjected to testing via conformation sensitive gel electrophoresis (CSGE), single-stranded conformational-polymorphism (SSCP), denaturing gradient gel electrophoresis (DGGE), or other means deemed most appropriate, to confirm the presence of a mutation before use of further testing, such as sequencing, to delineate the exact nature of the mutation; used to expedite analysis when the disorder in question can be caused by numerous possible mutations within a gene

F

false negative result

A test result which indicates that an individual is unaffected and/or does not have a particular gene mutation when he or she is actually affected and/or does have a gene mutation; i.e., a negative test result in an affected individual

false paternity

Synonyms: alternate paternity, nonpaternity

The situation in which the alleged father of a particular individual is not the biological father

false positive result

A test result which indicates that an individual is affected and/or has a certain gene mutation when he or she is actually unaffected and/or does not have the mutation; i.e., a positive test result in a truly unaffected individual

familial

A phenotype that occurs in more than one family member; may have genetic or non-genetic etiology

family history

The genetic relationships and medical history of a family; when represented in diagram form using standardized symbols and terminology, usually referred to as a pedigree

Related Terms: pedigree

family-specific mutation

In a family, the sequence alteration observed that causes or predisposes to a particular disease; the mutation may be rare or common

Family-specific mutation analysis

Testing for the specific disease-causing mutation(s) previously identified in a family member. Note: Family-specific mutation analysis is different from targeted mutation analysis

first-degree relative

Any relative who is one meiosis away from a particular individual in a family (i.e., parent, sibling, offspring)

Related Terms: family history; pedigree; second-degree relative

Image LearnMore.jpg

FISH

Synonym: fluorescent in situ hybridization

A technique used to identify the presence of specific chromosomes or chromosomal regions through hybridization (attachment) of fluorescently-labeled DNA probes to denatured chromosomal DNA. Examination under fluorescent lighting detects the presence of the hybridized fluorescent signal (and hence presence of the chromosome material) or absence of the hybridized fluorescent signal (and hence absence of the chromosome material).

Image LearnMore.jpg

FISH-interphase

A technique used to identify the presence of specific chromosomes or chromosomal regions through hybridization (attachment) of fluorescently-labeled DNA probes to denatured chromosomal DNA. Examination under fluorescent lighting detects the presence of the hybridized fluorescent signal (and hence presence of the chromosome material) or absence of the hybridized fluorescent signal (and hence absence of the chromosome material). With interphase FISH, probes are introduced directly to the interphase cell. Interphase FISH is often used for rapid detection of specific types of aneuploidy in fetal cells and for the detection of certain deletions, duplications and other abnormalities in tumor cells. In contract to metaphase FISH, interphase FISH does not permit visualization of the actual chromosomes; therefore, certain structural rearrangements or aneuploidy will not be detected.

Related Terms: aneuploidy; FISH-metaphase; probe

FISH-metaphase

A technique used to identify the presence of specific chromosomes or chromosomal regions through hybridization (attachment) of fluorescently-labeled DNA probes to denatured chromosomal DNA. Examination under fluorescent lighting detects the presence of the hybridized fluorescent signal (and hence presence of the chromosome material) or absence of the hybridized fluorescent signal (and hence absence of the chromosome material). With metaphase FISH, cells progress through the division process until metaphase, when chromosomes are condensed and can be individually distinguished. In contrast to interphase FISH, metaphase FISH permits visualization of the actual chromosomes as well as the general location of the abnormality on the chromosome.

Related Terms: FISH-interphase; probe

flanking marker

An identifiable, polymorphic region of DNA (i.e., marker) located to the side of a gene (i.e., flanking), as opposed to an intragenic marker which is located within the gene itself. Flanking markers are used in linkage analysis to track the coinheritance of the gene in question.

flanking microsatellite analysis

The use of highly variable repetitive sequences found in microsatellite regions adjacent to genes or other areas of interest as markers for linkage analysis, DNA fingerprinting, or other diagnostic application

fluorescent in situ hybridization

Synonym: FISH

A technique used to identify the presence of specific chromosomes or chromosomal regions through hybridization (attachment) of fluorescently-labeled DNA probes to denatured chromosomal DNA. Examination under fluorescent lighting detects the presence of the hybridized fluorescent signal (and hence presence of the chromosome material) or absence of the hybridized fluorescent signal (and hence absence of the chromosome material).

Image LearnMore.jpg

founder effect

A gene mutation observed in high frequency in a specific population due to the presence of that gene mutation in a single ancestor or small number of ancestors

Related Terms: allele frequency; population risk

Image LearnMore.jpg

frameshift mutation

Synonyms: out-of-frame mutation, out-of-frame deletion

An insertion or deletion involving a number of base pairs that is not a multiple of three and consequently disrupts the triplet reading frame, usually leading to the creation of a premature termination (stop) codon and resulting in a truncated protein product

full penetrance allele

In autosomal dominant, autosomal recessive, and X-linked disorders caused by nucleotide repeat expansion, an abnormally large allele that is associated with disease manifestations

Related Terms: anticipation; mutable normal allele; reduced penetrance allele; trinucleotide repeat; trinucleotide repeat testing

Image LearnMore.jpg Image CaseExample.jpg

G

gametogenesis

Synonyms: spermatogenesis, oogenesis

The meiotic process by which mature gametes (ova and sperm) are formed. Oogenesis refers specifically to the production of ova and spermatogenesis to the production of sperm.

gene

The basic unit of heredity, consisting of a segment of DNA arranged in a linear manner along a chromosome. A gene codes for a specific protein or segment of protein leading to a particular characteristic or function.

Related Terms: allele; genome; genotype; mutation

Image LearnMore.jpg

gene conversion

The transfer of DNA sequences between two very similar genes, most often by unequal crossing over during meiosis; can be a mechanism for mutation if the transfer of material disrupts the coding sequence of the gene or if the transferred material itself contains one or more mutations

Related Terms: pseudogene; recombination; unequal crossing over

Image DiseaseExample.jpg Image LearnMore.jpg

gene product

Genes are transcribed into segments of RNA (ribonucleic acid), which are translated into proteins. Both RNA and proteins are products of the expression of the gene.

Related Terms: DNA; dosage analysis; gene; isoforms; protein truncation testing; RNA; transcription; translation

Image LearnMore.jpg

gene symbol

A unique abbreviation of a gene name consisting of italicized uppercase Latin letters and Arabic numbers formally assigned by the by HUGO Gene Nomenclature Committee after a gene has been identified (Note: a putative gene may be referred to by its locus name prior to its identification)

Related Terms: locus name

Image LearnMore.jpg

gene therapy

Experimental treatment of a genetic disorder by replacing, supplementing, or manipulating the expression of abnormal genes with normally functioning genes

gene transfer

The transfer of genetic material, ranging from a small segment of DNA to the entire genome, from a human cell to another type of cell in culture in order to study the frequency with which known genetic markers are transferred together to the recipient genome; used to determine the physical proximity of genetic markers in the human genome; also used to study gene expression and regulation

genetic counseling

A process, involving an individual or family, comprising: evaluation to confirm, diagnose, or exclude a genetic condition, malformation syndrome, or isolated birth defect; discussion of natural history and the role of heredity; identification of medical management issues; calculation and communication of genetic risks; provision of or referral for psychosocial support

genetic predisposition

Synonym: genetic susceptibility

Increased susceptibility to a particular disease due to the presence of one or more gene mutations associated with an increased risk for the disease and/or a family history that indicates an increased risk for the disease

genome

The complete DNA sequence, containing all genetic information and supporting proteins, in the chromosomes of an individual or species

genotype

The genetic constitution of an organism or cell; also refers to the specific set of alleles inherited at a locus

genotype-phenotype correlation

The association between the presence of a certain mutation or mutations (genotype) and the resulting pattern of abnormalities (phenotype)

Related Terms: genotype; phenotype

Image LearnMore.jpg

genotyping

Testing that reveals the specific alleles inherited by an individual; particularly useful for situations in which more than one genotypic combination can produce the same clinical presentation, as in the ABO blood group, where both the AO and AA genotypes yield type A blood

germline

The cell line from which egg or sperm cells (gametes) are derived

germline mosaicism

Two or more genetic or cytogenetic cell lines confined to the precursor (germline) cells of the egg or sperm; formerly called gonadal mosaicism

germline mutation

The presence of an altered gene within the egg or sperm (germ cell), such that the altered gene can be passed to subsequent generations

Related Terms: de novo mutation; germline; germline mosaicism

Image LearnMore.jpg Image CaseExample.jpg

gonadal mosaicism

See germline mosaicism.

H

haploid

Half the diploid or normal number of chromosomes in a somatic cell; the number of chromosomes in a gamete (egg or sperm) cell, which in humans is 23 chromosomes, one chromosome from each chromosome pair

haploinsufficiency

The situation in which an individual who is heterozygous for a certain gene mutation or hemizygous at a particular locus, often due to a deletion of the corresponding allele, is clinically affected because a single copy of the normal gene is incapable of providing sufficient protein production as to assure normal function

haplotype analysis

Molecular genetic testing to identify a set of closely linked segments of DNA; used in linkage analysis or when a given trait is in linkage disequilibrium with a marker or set of markers

hemizygous

The situation in which an individual has only one member of a chromosome pair or chromosome segment rather than the usual two; refers in particular to X-linked genes in males who under normal circumstances have only one X chromosome

Related Terms: heterozygote; homologous chromosomes; homozygote; X-linked dominant; X-linked recessive

Image LearnMore.jpg

heteroplasmy

The situation in which, within a single cell, there is a mixture of mitochondria (energy producing cytoplasmic organelles), some containing mutant DNA and some containing normal DNA

Related Terms: mitochondrial inheritance; pleiotropy; variable expressivity

heterozygote

An individual who has two different alleles at a particular locus, one on each chromosome of a pair; one allele is usually normal and the other abnormal

Related Terms: carrier; homozygote; obligate carrier; obligate heterozygote

Image LearnMore.jpg Image CaseExample.jpg

high-resolution chromosome studies

Analysis of the number and structure of the chromosomes when cell division has been arrested and the chromosomes stained at an early stage (pro-metaphase) of mitosis. The chromosomes of a high resolution study appear longer and reveal 700-1200 bands, allowing more detailed analysis of the chromosome structure, as opposed to the typical 300-600 bands observed with routine metaphase banding.

homologous chromosomes

Synonym: homologs

The two chromosomes from a particular pair, normally one inherited from the mother and one from the father, containing the same genetic loci in the same order

Related Terms: chromosome; cytogenetics; hemizygous; karyotype; monosomy; polyploidy; recombination; trisomy; trisomy rescue; uniparental disomy

Image LearnMore.jpg

homozygote

An individual who has two identical alleles at a particular locus, one on each chromosome of a pair

Related Terms: compound heterozygote; heterozygote

Image LearnMore.jpg Image CaseExample.jpg

hotspot mutation region

DNA sequences of high susceptibility to mutation due to some inherent instability, tendency toward unequal crossing over, or chemical predisposition to single nucleotide substitutions; region where mutations are observed with greater frequency

I

immunohistochemistry

Testing to detect the presence of specific proteins in cells or tissues by means of a specific antigen/antibody reaction tagged with a visible label

imprinting

The process by which maternally and paternally derived chromosomes are uniquely chemically modified leading to different expression of a certain gene or genes on those chromosomes depending on their parental origin

Related Terms: trisomy rescue; uniparental disomy

Image LearnMore.jpg Image CaseExample.jpg

in-frame mutation

A mutation that does not cause a shift in the triplet reading frame; such mutations can, however, lead to the synthesis of an abnormal protein product

incomplete autosomal dominant

An inheritance pattern in which the phenotypes observed lie on a continuum (differing in degree or kind) depending on whether one or two mutated alleles are present

informativeness

In linkage analysis, the ability to distinguish between maternally-inherited and paternally-inherited DNA markers (polymorphisms) within or near a given gene of interest

Related Terms: haplotype analysis; linkage analysis; polymorphism

Image LearnMore.jpg

Permission given by an individual to proceed with a specific test or procedure, with an understanding of the risks, benefits, limitations, and potential implications of the procedure itself and its results

insertion

A chromosome abnormality in which material from one chromosome is inserted into another nonhomologous chromosome; a mutation in which a segment of DNA is inserted into a gene or other segment of DNA, potentially disrupting the coding sequence

interfamilial variability

Variability in clinical presentation of a particular disorder among affected individuals from different families

intrafamilial variability

Variability in clinical presentation of a particular disorder among affected individuals within the same immediate or extended family

intragenic marker

An identifiable, polymorphic region of DNA (i.e., marker) located within a gene (i.e., intragenic), as opposed to a flanking marker, which is located on either side of a gene. Intragenic markers are used in linkage analysis to track the coinheritance of the gene in question.

intron

Non-coding sequence of DNA removed from mature messenger RNA prior to translation

Related Terms: coding region; exon; intronic mutation; RNA; splicing; transcription; translation

Image LearnMore.jpg

intronic mutation

A mutation (usually a base substitution) within an intron that creates an alternative splice site that competes with the normal splice sites during RNA processing. Such a mutation results in a proportion of mature messenger RNA with improperly spliced intron sequences.

inversion

A chromosomal rearrangement in which a segment of a chromosome has inverted from end to end, and re-inserted into the chromosome at the same breakage site. Balanced inversions (in which no net loss or gain of genetic material occurs) are usually not associated with phenotypic abnormalities, however, in some cases, gene disruptions at the breakpoints can cause adverse phenotypic effects, including some known genetic diseases. Unbalanced inversions (in which loss or gain of chromosome material occurs) nearly always yield an abnormal phenotype.

isoelectric focusing

Method of mutation detection by which proteins are separated according to the pH at which their net charge is zero (isoelectric point); often used in conjunction with a western blot to allow identification of wild-type versus mutant protein products. A DNA sequence alteration resulting in an amino acid substitution can change the isoelectric point of a protein.

isoforms

The protein products of different versions of messenger RNA created from the same gene by employing different promoters, which causes transcription to skip certain exons. Since the promoters are tissue-specific, different tissues express different protein products of the same gene.

isolated

An abnormality that occurs in the absence of other systemic involvement

K

karyotype

A photographic representation of the chromosomes of a single cell, cut and arranged in pairs based on their size and banding pattern according to a standard classification

Image LearnMore.jpg

kindred

An extended family; term often used in linkage studies to refer to large families

Known family-specific mutations

A specific disease-causing mutation identified in an affected family member; testing is recommended for other at-risk family members who might have that specific mutation; for example, if sequence analysis identifies a disease-causing mutation in an affected family member, all at-risk relatives need only to be tested for their family-specific mutation.

L

linkage

The tendency for genes or segments of DNA closely positioned along a chromosome to segregate together at meiosis and therefore be inherited together

linkage analysis

Synonym: indirect DNA analysis

Testing DNA sequence polymorphisms (normal variants) that are near or within a gene of interest to track within a family the inheritance of a disease-causing mutation in a given gene

Related Terms: direct DNA analysis; haplotype analysis; polymorphism; recombination

Image LearnMore.jpg

locus

The physical site or location of a specific gene on a chromosome

locus heterogeneity

The situation in which mutations in genes at different chromosomal loci cause the same phenotype

Related Terms: allele; allelic heterogeneity; genotype; locus; mutation; phenotype

Image LearnMore.jpg Image CaseExample.jpg

locus name

An informally assigned abbreviation used in the process of mapping to designate a putative gene prior to gene identification; once the gene is identified. The locus name is generally replaced by a formally assigned gene symbol (which often differs from the locus name).

loss of heterozygosity

Synonym: LOH

At a particular locus heterozygous for a deleterious mutant allele and a normal allele, a deletion or other mutational event within the normal allele renders the cell either hemizygous (one deleterious allele and one deleted allele) or homozygous for the deleterious allele

Related Terms: deletion; hemizygous; heterozygote; homozygote

Image DiseaseExample.jpg Image LearnMore.jpg

lyonization

Synonym: X-chromosome inactivation

The phenomenon in females by which one X chromosome (either maternally derived or paternally derived) is randomly inactivated in early embryonic cells, with fixed inactivation in all descendant cells; first described by the geneticist Mary Lyon

Related Terms: mosaicism; replication analysis; X-chromosome inactivation study; X-linked dominant; X-linked recessive

Image LearnMore.jpg Image CaseExample.jpg

M

manifesting carrier

An individual who has, at a particular locus, a recessive, disease-causing allele on one chromosome and a normal allele on the other chromosome and who manifests some symptoms of the disorder; generally refers to female carriers of an X-linked recessive mutation who are clinically affected, although the phenotype is usually less severe as compared to males with the same mutation

Related Terms: carrier; heterozygote; lyonization; X-chromosome inactivation; X-chromosome inactivation study; X-linked recessive

Image LearnMore.jpg Image CaseExample.jpg

mapped gene

Synonym: mapped phenotype

A gene or phenotype whose relative position on a segment of DNA or on a chromosome has been established

marker

An identifiable segment of DNA (e.g., RFLP, VNTR, microsatellite) with enough variation between individuals that its inheritance and co-inheritance with alleles of a given gene can be traced; used in linkage analysis

marker chromosome

A small chromosome containing a centromere occasionally seen in tissue culture, often in a mosaic state (present in some cells but not in others). A marker chromosome may be of little clinical significance or, if it contains material from one or both arms of another chromosome, may create an imbalance for whatever genes are present; assessment to establish clinical significance, particularly if found in a fetal karyotype, is often difficult.

Related Terms: supernumary chromosome

maternal contamination

The situation which occurs in prenatal testing in which a sample of chorionic villus, amniotic fluid, or umbilical blood becomes contaminated with maternal (usually blood) cells, which can confound interpretation of the results of genetic analysis

methylation

The attachment of methyl groups to DNA at cytosine bases; correlated with reduced transcription of the gene and thought to be the principal mechanism in X-chromosome inactivation and imprinting

methylation analysis

Testing that evaluates the methylation status of a gene (attachment of methyl groups to DNA cytosine bases); genes that are methyalted are not expressed; methylation plays a role in X-chromosome inactivation and imprinting

Related Terms: Analysis of the entire coding region: Sequence analysis; imprinting; methylation; Southern blot; X-chromosome inactivation study

Image LearnMore.jpg Image CaseExample.jpg

microdeletion syndrome

Synonym: contiguous gene deletion syndrome

A syndrome caused by a chromosomal deletion spanning several genes that is too small to be detected under the microscope using conventional cytogenetic methods. Depending on the size of the deletion, other techniques, such as FISH or other methods of DNA analysis can sometimes be employed to identify the deletion

microsatellite

Synonyms: satellite DNA, short tandem repeats

Repetitive segments of DNA two to five nucleotides in length (dinucleotide/trinucleotide/tetranucleotide/pentanucleotid e repeats), scattered throughout the genome in non-coding regions between genes or within genes (introns), often used as markers for linkage analysis because of the naturally occurring high variability in repeat number between individuals. These regions are inherently unstable and susceptible to mutations.

microsatellite instability

Synonyms: replication error phenotype, MSI, RER

The presence of a discrepancy between the size of microsatellites in DNA from tumor tissue compared to nontumor tissue from the same person, resulting from mutations in a gene in the DNA mismatch repair pathway (MMR) that would normally correct these errors.

microsatellite instability testing

Synonym: MSI testing

Used to identify tumors caused by defective mismatch repair by comparing the number of nucleotide repeats in a panel of microsatellite markers in normal tissue with the number from tumor tissue from the same individual. Microsatellite stability (MSS) is present if the same number of repeats is present in each marker in both the tumor and the normal tissue. Microsatellite instability (MSI) is present if the number of repeats in the tumor and the normal tissue differs.

Related Terms: microsatellite; microsatellite instability; mismatch repair mechanism

Image LearnMore.jpg Image CaseExample.jpg

mismatch repair mechanism

Synonym: mismatch repair

The DNA 'proof-reading' system controlled by certain genes that identifies, excises, and corrects errors in the pairing of the bases during DNA replication. Mutations in the genes responsible for this mechanism can lead to certain genetic diseases and some forms of cancer.

missense mutation

A single base pair substitution that results in the translation of a different amino acid at that position

mitochondrial inheritance

Mitochondria, cytoplasmic organelles that produce the energy source ATP for most chemical reactions in the body, contain their own distinct genome; mutations in mitochondrial genes are responsible for several recognized syndromes and are always maternally inherited since ova contain mitochondria, whereas sperm do not

Related Terms: heteroplasmy; mode of inheritance; penetrance; pleiotropy; variable expressivity

Image LearnMore.jpg Image CaseExample.jpg

mode of inheritance

Synonyms: inheritance pattern, pattern of inheritance

The manner in which a particular genetic trait or disorder is passed from one generation to the next. Autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, multifactorial, and mitrochondrial inheritance are examples

molecular genetic testing

Synonyms: DNA-based testing, molecular testing, DNA testing

Testing that involves the analysis of DNA, either through linkage analysis, sequencing, or one of several methods of mutation detection

monosomy

The presence of only one chromosome from a pair; partial monosomy refers to the presence of only one copy of a segment of a chromosome

mosaicism

Within a single individual or tissue, the occurrence of two or more cell lines with different genetic or chromosomal constitutions

Related Terms: germline mutation; post-zygotic event

Image LearnMore.jpg Image CaseExample.jpg

Multicolor FISH (M-FISH)/Spectral Karyotyping(™) (SKY(™))

Synonyms: Multi-color-FISH, Multi-FISH, Multi-target

SKY and M-FISH utilize "whole chromosome paint" DNA probes, which are labeled with a unique fluorescent color for each of the 24 human chromosomes. The technique visualizes and thus identifies chromosomal material in marker chromosomes and subtle translocations whose origin cannot be determined by other cytogenetic techniques.

multifactorial inheritance

Synonym: polygenic

The combined contribution of one or more often unspecified genes and environmental factors, often unknown, in the causation of a particular trait or disease

mutable normal allele

Synonyms: intermediate allele, mutable normal allele

In disorders caused by nucleotide repeat expansion, an abnormally large allele that is not associated with clinical symptoms but that can expand into a reduced penetrance allele or a full penetrance allele when transmitted to offspring. Mutable normal alleles are larger than normal alleles and smaller than reduced penetrance alleles and full penetrance alleles.

Related Terms: anticipation; full penetrance allele; reduced penetrance allele; trinucleotide repeat; trinucleotide repeat testing

Image LearnMore.jpg Image CaseExample.jpg

mutation

Synonyms: sequence alteration, splicing mutation

Any alteration in a gene from its natural state; may be disease-causing or a benign, normal variant

Related Terms: allelic variant of unknown significance; benign variant; deletion; disease-causing mutation; frameshift mutation; in-frame mutation; point mutation; polymorphism; trinucleotide repeat

Image LearnMore.jpg

mutation scanning

A process by which a segment of DNA is screened via one of a variety of methods to identify variant gene region(s). Variant regions are further analyzed (by sequence analysis or mutation analysis) to identify the sequence alteration.

Related Terms: CSGE; DGGE; DNA-based testing; molecular genetic testing; PCR; sequence analysis; SSCP; Targeted mutation analysis

Image LearnMore.jpg

Mutation scanning of select exons

A 2-step process by which specific exons of a gene are first analyzed via one of a variety of methods (such as CSGE, DGGE, SSCP, DHPLC or TGCE) to identify sequence alternations. These methods do not identify the specific nucleotide change(s) and must be followed by further analysis (usually sequencing) to identify the specific sequence alteration

N

negative predictive value

The likelihood that an individual with a negative test result is actually unaffected and/or does not have the particular gene mutation in question

newborn screening

Testing done within days of birth to identify infants at increased risk for a specific genetic disorder so that treatment can begin as soon as possible; when a newborn screening result is positive, further diagnostic testing is usually required to confirm or specify the results and counseling is offered to educate the parents

Related Terms: diagnostic testing; screening; sensitivity; specificity

Image DiseaseExample.jpg Image LearnMore.jpg

nonsense mutation

A single base pair substitution that prematurely codes for a stop in amino acid translation (stop codon)

northern blot

Synonym: northern blotting analysis

The separation of sequences or fragments of RNA, partially digested by endonucleases, on an electrophoretic gel

novel mutation

A distinct gene alteration that has been newly discovered; not the same as a 'new' or 'de novo' mutation

nucleotide

A molecule consisting of a nitrogenous base (adenine, guanine, thymine, or cytosine in DNA; adenine, guanine, uracil, or cytosine in RNA), a phosphate group, and a sugar (deoxyribose in DNA; ribose in RNA). DNA and RNA are polymers of many nucleotides.

null allele

A mutation that results in either no gene product or the absence of function at the phenotypic level

O

obligate carrier

Synonym: obligate heterozygote

An individual who may be clinically unaffected but who must carry a gene mutation based on analysis of the family history; usually applies to disorders inherited in an autosomal recessive or X-linked recessive manner

Related Terms: autosomal dominant; carrier; heterozygote; X-linked dominant; X-linked recessive

Image LearnMore.jpg Image CaseExample.jpg

obligate heterozygote

Synonym: obligate heterozygote

An individual who may be clinically unaffected but who must carry a gene mutation based on analysis of the family history; usually applies to disorders inherited in an autosomal recessive and X-linked recessive manner

open reading frame

Synonym: ORF

All exons of a gene that contribute to the protein product(s) of the gene

P

paracentric inversion

An inversion in which the breakpoints are confined to one arm of a chromosome; the inverted segment does not span the centromere

parent-of-origin studies

An analysis used to determine whether a particular chromosome or segment of DNA was inherited from an individual's mother or father; helpful in the diagnosis of disorders in which imprinting or uniparental disomy is a possible underlying etiological mechanism

parentage testing

Synonyms: paternity testing, maternity testing

The process through which DNA sequences from a particular child and a particular adult are compared to estimate the likelihood that the two individuals are related; DNA testing can reliably exclude but cannot absolutely confirm an individual as a biological parent

PCR

Synonym: polymerase chain reaction

A procedure that produces millions of copies of a short segment of DNA through repeated cycles of: 1) denaturation, 2) annealing, and 3) elongation; PCR is a very common procedure in molecular genetic testing and may be used to: 1) generate a sufficient quantity of DNA to perform a test (e.g., sequence analysis, mutation scanning), or 2) may be a test in and of itself (e.g., allele-specific amplification, trinucleotide repeat quantification).

Related Terms: Analysis of the entire coding region: Mutation scanning; Analysis of the entire coding region: Sequence analysis; conformation-sensitive gel electrophoresis; denaturing gradient gel electrophoresis; restriction fragment length polymorphism analysis; single-stranded conformational polymorphism; Southern blot; Targeted mutation analysis; X-chromosome inactivation study

Image LearnMore.jpg

pedigree

A diagram of the genetic relationships and medical history of a family using standard symbols and terminology

Related Terms: consanguinity; consultand; obligate carrier; proband

Image LearnMore.jpg Image CaseExample.jpg

penetrance

The proportion of individuals with a mutation causing a particular disorder who exhibit clinical symptoms of that disorder; most often refers to autosomal dominant conditions.

Related Terms: autosomal dominant; intrafamilial variability; variable expressivity

Image LearnMore.jpg Image CaseExample.jpg

pericentric inversion

An inversion in which the breakpoints occur on both arms of a chromosome. The inverted segment spans the centromere.

phenotype

The observable physical and/or biochemical characteristics of the expression of a gene; the clinical presentation of an individual with a particular genotype

Related Terms: allelic heterogeneity; dysmorphology; genotype; genotype-phenotype correlation; locus heterogeneity; variable expressivity

Image LearnMore.jpg

phenotyping

Diagnostic testing and inference of a particular genotype based on clinical or biochemical presentation (phenotype) of the individual, such as measurement of alpha-1-antitrypsin level, which is greatly reduced in individuals homozygous for the Z allele. With the advent of DNA-based testing, direct mutation analysis (genotyping) is becoming more widely available for many disorders.

pleiotropy

Multiple, often seemingly unrelated, physical effects caused by a single altered gene or pair of altered genes

point mutation

An alteration in DNA sequence caused by a single nucleotide base change, insertion, or deletion

polygenic

A condition caused by the additive contributions of mutations in multiple genes at different loci

polymerase chain reaction (PCR)

A procedure that produces millions of copies of a short segment of DNA through repeated cycles of: 1) denaturation, 2) annealing, and 3) elongation; PCR is a very common procedure in molecular genetic testing and may be used to: 1) generate a sufficient quantity of DNA to perform a test (e.g., sequence analysis, mutation scanning), or 2) may be a test in and of itself (e.g., allele-specific amplification, trinucleotide repeat quantification).

Related Terms: Analysis of the entire coding region: Mutation scanning; Analysis of the entire coding region: Sequence analysis; conformation-sensitive gel electrophoresis; denaturing gradient gel electrophoresis; restriction fragment length polymorphism analysis; single-stranded conformational polymorphism; Southern blot; Targeted mutation analysis; X-chromosome inactivation study

Image LearnMore.jpg

polymorphism

Natural variations in a gene, DNA sequence, protein, or chromosome that have no adverse effect on the individual and occur with fairly high frequency in the general population

Related Terms: allele; allelic variant of unknown significance; benign variant; mutation; restriction fragment length polymorphism

Image LearnMore.jpg

polyploidy

An increase in the number of haploid sets (23) of chromosomes in a cell. Triploidy refers to three whole sets of chromosomes in a single cell (in humans, a total of 69 chromosomes per cell); tetraploidy refers to four whole sets of chromosomes in a single cell (in humans, a total of 92 chromosomes per cell).

population risk

Synonym: background risk

The proportion of individuals in the general population who are affected with a particular disorder or who carry a certain gene; often discussed in the genetic counseling process as a comparison to the patient's personal risk given his or her family history or other circumstances

positional cloning

Synonym: reverse genetics

The cloning or identification of a gene for a particular disease based on its location in the genome, determined by a collection of methods including linkage analysis, genomic (physical) mapping, and bioinformatics, when no information about the biochemical basis of the disease is known; distinguished from the more common strategy of gene cloning beginning with a known protein product, determining its amino acid sequence, and using that information to isolate the gene

positive predictive value

Synonym: PPV

The likelihood that an individual with a positive test result actually has the particular gene in question, is affected, or will develop the disease

post-zygotic event

A mutational event or abnormality in chromosome replication/segregation that occurs after fertilization of the ovum by the sperm, often leading to mosaicism (two or more genetically distinct cell lines within the same organism)

Related Terms: germline mosaicism; mosaicism; somatic mosaicism; trisomy rescue

Image LearnMore.jpg

predictive testing

Testing offered to asymptomatic individuals with a family history of a genetic disorder and a potential risk of eventually developing the disorder

Related Terms: disease-causing mutation; DNA-based testing; molecular genetic testing; predisposing mutation; susceptibility gene

Image DiseaseExample.jpg Image LearnMore.jpg

predisposing mutation

Synonym: susceptibility gene

A gene mutation that increases an individual's susceptibility or predisposition to a certain disease or disorder. When such a mutation is inherited, development of symptoms is more likely but not certain.

predispositional testing

Testing of an asymptomatic individual in whom the discovery of a gene mutation indicates that eventual development of findings related to a specific diagnosis is likely but not certain. A negative result may not exclude the possibility of future development of the disease from other causes.

preimplantation diagnosis

Synonym: preimplantation testing

A procedure used to decrease the chance of a particular genetic condition for which the fetus is specifically at risk by testing one cell removed from early embryos conceived by in vitro fertilization and transferring to the mother's uterus only those embryos determined not to have inherited the mutation in question

Related Terms: diagnostic testing; direct DNA analysis; DNA-based testing; molecular genetic testing; polymerase chain reaction (PCR); prenatal diagnosis; Targeted mutation analysis

Image LearnMore.jpg Image CaseExample.jpg

prenatal diagnosis

Synonym: prenatal testing

Testing performed during pregnancy to determine if a fetus is affected with a particular disorder. Chorionic villus sampling (CVS), amniocentesis, periumbilical blood sampling (PUBS), ultrasound, and fetoscopy are examples of procedures used either to obtain a sample for testing or to evaluate fetal anatomy.

Related Terms: diagnostic testing; screening

Image LearnMore.jpg Image CaseExample.jpg

presymptomatic testing

Testing of an asymptomatic individual in whom the discovery of a gene mutation indicates certain development of findings related to a specific diagnosis at some future point. A negative result excludes the diagnosis.

private mutation

Synonym: unique mutation

A rare disease-causing mutation observed in a few families

proband

Synonyms: propositus, index case

The affected individual through whom a family with a genetic disorder is ascertained; may or may not be the consultand (the individual presenting for genetic counseling)

Related Terms: affected; consultand; pedigree

Image LearnMore.jpg

probe

A specific, pre-fabricated sequence of DNA or RNA, labeled by one of several methods, used to detect the presence of a complimentary sequence by binding (hybridizing) to it

Related Terms: FISH; restriction fragment length polymorphism analysis; Southern blot; Targeted mutation analysis

Image LearnMore.jpg

promoter region

A specific region just upstream from a gene that acts as a binding site for transcription factors and RNA polymerase during the initiation of transcription

protein analysis

One of several different testing methods that reveals either the structure or function of a particular protein product

protein expression

Testing to examine the expression of a mutation in a recombinant protein to confirm its pathogenicity

protein functional assay

Measurement of the rate of a chemical reaction that takes place in the presence of an enzyme contained in a sample taken from an individual. Reduced enzymatic activity may indicate carrier status or the diagnosis of a particular genetic disease

protein truncation testing

Synonym: PTT

Means of identifying the shortened (truncated) proteins that result from mutations which specifically cause premature termination of mRNA translation

Related Terms: direct DNA analysis; PCR; western blot

Image DiseaseExample.jpg Image LearnMore.jpg

pseudodominant inheritance

An autosomal recessive condition present in individuals in two or more generations of a family, thereby appearing to follow a dominant inheritance pattern. Common explanations include: 1) a high carrier frequency; 2) birth of an affected child to an affected individual and a genetically related (consanguineous) reproductive partner

pseudogene

A copy of a gene that usually lacks introns and other essential DNA sequences necessary for function; pseudogenes, though genetically similar to the original functional gene, are not expressed and often contain numerous mutations

Related Terms: deletion; duplication; gene conversion; unequal crossing over

Image LearnMore.jpg

Q

quantitative PCR

Synonyms: real time quantitative PCR, kinetic quantitative PCR

The use of PCR to determine the amount of DNA or RNA in a sample; commonly used to detect heterozygous deletion mutations and duplication mutations

Related Terms: deletion; duplication; heterozygote; PCR; Targeted mutation analysis

Image LearnMore.jpg

R

radiosensitivity testing

Synonyms: colony survival essay, CSA

Testing specific to ataxia-telangiectasia (A-T) and other disorders in which cells are particularly sensitive to ionizing radiation; demonstrates colony formation of a blood lymphocyte cell line following irradiation, which is abnormal in approximately 99% of patients with clinically diagnosed A-T, though the sensitivity of such testing in light of a suspected but unsure diagnosis of A-T has not yet been documented

reading frame

Synonym: exon

A sequence of messenger RNA that is translated into an amino acid chain, three bases at a time, each triplet sequence coding for a single amino acid

rearrangement

A structural alteration in a chromosome, usually involving breakage and reattachment of a segment of chromosome material, resulting in an abnormal configuration; examples include inversion and translocation

recessive

See autosomal recessive.

reciprocal translocation

A segment of one chromosome is exchanged with a segment of another chromosome of a different pair

Related Terms: chromosome; deletion; derivative chromosome; duplication; trisomy

Image LearnMore.jpg Image CaseExample.jpg

recombination

Synonym: crossing over

The exchange of a segment of DNA between two homologous chromosomes during meiosis leading to a novel combination of genetic material in the gamete

Image LearnMore.jpg Image CaseExample.jpg

recurrence risk

The likelihood that a trait or disorder present in one family member will occur again in other family members in the same or subsequent generations

reduced penetrance allele

Synonym: intermediate allele

In autosomal dominant disorders caused by nucleotide repeat expansion, an abnormally large allele that may or may not result in an abnormal phenotype in a normal life span. The abnormal phenotype may be very-late-onset disease and/or a different phenotype. Reduced penetrance alleles are larger than mutable normal alleles and smaller than full penetrance alleles.

Related Terms: anticipation; full penetrance allele; mutable normal allele; trinucleotide repeat; trinucleotide repeat testing

Image LearnMore.jpg Image CaseExample.jpg

reflex testing

Follow-up testing automatically initiated when certain test results are observed in the laboratory; used to clarify or elaborate on primary test results

replication analysis

Synonyms: XCI, replication banding, X-chromosome inactivation study

A cytogenetic technique that uses specialized banding procedures (replication banding) to identify the late-replicating (inactive) X chromosome in cells. Because it is less complicated, less expensive, and less subjective, molecular testing is now used more commonly than replication analysis for X-chromosome inactivation studies.

restriction fragment length polymorphism

Synonym: RFLP

Natural (polymorphic) variation in DNA sequence between individuals which abolishes or creates endonuclease restriction (cutting) sites, resulting in DNA fragments of different lengths when DNA is digested by an endonuclease

restriction fragment length polymorphism analysis

Synonyms: RFLP analysis, RFLP testing

Fragment of DNA of predictable size resulting from digestion (cutting) of a strand of DNA by a given restriction enzyme. DNA sequence alterations (mutations) that destroy or create the sites at which a restriction enzyme cuts DNA change the size (and number) of DNA fragments resulting from digestion by a given restriction enzyme.

Related Terms: DNA-based testing; molecular genetic testing; polymerase chain reaction (PCR); Southern blot; Targeted mutation analysis

Image LearnMore.jpg Image CaseExample.jpg

restriction site

A sequence of DNA that is recognized by an endonuclease (a protein that cuts DNA) as a site at which the DNA is to be cut

risk assessment

Calculation of an individual's risk, employing appropriate mathematical equations, of having inherited a certain gene mutation, of developing a particular disorder, or of having a child with a certain disorder based upon analysis of multiple factors including family medical history and ethnic background

risk assessment modification

Alteration of the assessment of an individual's genetic risk based upon previously unknown information about the family history or upon the results of genetic testing; depending on the nature of the new information, risk may be either increased or decreased

Related Terms: background risk; population risk; risk assessment

Image LearnMore.jpg Image CaseExample.jpg

RNA

Synonym: ribonucleic acid

The molecule synthesized from the DNA template; contains the sugar ribose instead of deoxyribose, which is present in DNA; three types of RNA exist, messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA)

Robertsonian translocation

The joining of two acrocentric chromosomes at the centromeres with loss of their short arms to form a single abnormal chromosome; in acrocentric chromosomes the centromere is located near the end of the chromosome; acrocentric chromosomes are the Y chromosome and chromosome numbers 13, 14, 15, 21, and 22

Related Terms: chromosome; deletion; derivative chromosome; duplication; trisomy

Image LearnMore.jpg Image CaseExample.jpg

S

screening

Testing designed to identify individuals in a given population who are at higher risk of having or developing a particular disorder, or having a gene mutation for a particular disorder

Related Terms: diagnostic testing; prenatal diagnosis

Image LearnMore.jpg Image CaseExample.jpg

second-degree relative

Any relative who is two meioses away from a particular individual in a pedigree; a relative with whom one quarter of an individual's genes is shared (i.e., grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling)

segregation

The separation of the homologous chromosomes and their random distribution to the gametes at meiosis

sensitivity

The frequency with which a test yields a positive result when the individual being tested is actually affected and/or has the gene mutation in question

sequence alteration

Synonym: mutation

Any alteration in a gene from its natural state; may be benign (commonly referred to as a "polymorphism"), pathogenic, or of unknown significance

sequence analysis

Synonyms: gene sequencing, sequencing

Process by which the nucleotide sequence is determined for a segment of DNA

Related Terms: direct DNA analysis; DNA-based testing; molecular genetic testing; mutation scanning; PCR; Targeted mutation analysis

Image LearnMore.jpg

Sequence analysis of select exons

The process by which specific exons are sequenced to identify sequence variations; used to expedite analysis when certain exons are likely to contain the disease-causing mutation(s)

simplex case

A single occurrence of a disorder in a family

single-stranded conformational polymorphism

Synonym: SSCP

A type of mutation scanning; the identification of abnormally migrating single-stranded DNA segments on gel electrophoresis

Related Terms: Analysis of the entire coding region: Mutation scanning; Analysis of the entire coding region: Sequence analysis; CSGE; DGGE; PCR; Targeted mutation analysis

Image LearnMore.jpg

sister chromatid exchange

Synonym: SCE

Exchange of genetic material between the two chromatids of a single chromosome during the cell division process; similar to crossing-over (recombination), except that the exchange involves the two sister chromatids of a single chromosome, whereas crossing-over refers to exchange of genetic material between the two homologous chromosomes of a chromosome pair

somatic mosaicism

Two or more genetic or cytogenetic cell lines within the cells of the body (may or may not include the germline cells)

Southern blot

Synonyms: Southern analysis, Southern blot analysis, Southern blotting, Southern blotting analysis

Molecular genetic testing technique used to detect differences in the lengths of DNA fragments following restriction enzyme digestion (commonly known as RFLPs: restriction fragment length polymorphisms). The lengths of restriction fragments can vary due to mutations occurring between two restriction sites (e.g., large insertions, large deletions, and highly expanded trinucleotide repeats) or within a restriction site (e.g., single base pair changes).

Related Terms: direct DNA analysis; molecular genetic testing; restriction fragment length polymorphism analysis; restriction site; Targeted mutation analysis

Image LearnMore.jpg

specificity

The frequency with which a test yields a negative result when the individual being tested is actually unaffected and/or does not have the gene mutation in question

splice-site mutation

A mutation that alters or abolishes the specific sequence denoting the site at which the splicing of an intron takes place. Such mutations result in one or more introns remaining in the mature messenger RNA and can disrupt the generation of the protein product

splicing

Synonym: splicing mutation

The process by which introns, non-coding regions, are excised out of the primary messenger RNA transcript and exons (i.e., coding regions) are joined together to generate mature messenger RNA

sporadic

The chance occurrence of a disorder or abnormality that is not likely to recur in a family

Related Terms: familial; isolated; recurrence risk; simplex case

Image LearnMore.jpg Image CaseExample.jpg

SSCP

Synonym: single-stranded conformational polymorphism

A type of mutation scanning; the identification of abnormally migrating single-stranded DNA segments on gel electrophoresis

Related Terms: Analysis of the entire coding region: Mutation scanning; Analysis of the entire coding region: Sequence analysis; CSGE; DGGE; PCR; Targeted mutation analysis

Image LearnMore.jpg

subtelomeric FISH screen

Uses DNA probes that are specific for the subtelomeric areas on the long arm and short arm of each chromosome, allowing for the detection of cryptic and submicroscopic subtelomeric deletions and translocations, a significant cause of moderate to severe mental retardation

subtelomeric region

The chromosomal region just proximal to the telomere (end of the chromosome) composed of highly polymorphic repetitive DNA sequences that are typically situated adjacent to gene-rich areas. Microdeletions and subtle rearrangements that disrupt genes in the subtelomeric regions can cause mental retardation; use of fluorescent in situ hybridization (FISH) to evaluate subtelomeric regions is usually required for detection of these abnormalities.

supernumary chromosome

A small chromosome containing a centromere occasionally seen in tissue culture, often in a mosaic state (present in some cells but not in others). A marker chromosome may be of little clinical significance or, if it contains material from one or both arms of another chromosome, may create an imbalance for whatever genes are present; assessment to establish the clinical significance, particularly if found in a fetal karyotype, is often difficult.

susceptibility gene

A gene mutation that increases the likelihood that an individual will develop a certain disease or disorder. When such a mutation is inherited, development of symptoms is more likely but not certain

T

Targeted mutation analysis

Synonym: allele-specific mutation analysis

Testing for either (1) a nucleotide repeat expansion (e.g., the trinucleotide repeat expansion associated with Huntington disease), or (2) one or more specific mutations (e.g., Glu6Val for sickle cell anemia, a panel of mutations for cystic fibrosis). Deletion/duplication analysis and family-specific mutation analysis are excluded from this definition

Related Terms: allele-specific oligonucleotide testing; Analysis of the entire coding region: Mutation scanning; Analysis of the entire coding region: Sequence analysis; Southern blot; trinucleotide repeat testing

Image LearnMore.jpg

telomere

The segment at the end of each chromosome arm which consists of a series of repeated DNA sequences that regulate chromosomal replication at each cell division. Some of the telomere is lost each time a cell divides, and eventually, when the telomere is gone, the cell dies.

trans configuration

Synonym: repulsion

Term which indicates that an individual who is heterozygous at two neighboring loci has the two mutations in question on each of the two homologous chromosomes

Related Terms: double heterozygote; pseudogene; variable expressivity

Image DiseaseExample.jpg Image LearnMore.jpg

transcription

The process of synthesizing messenger RNA (mRNA) from DNA

transcription factor

Synonym: zinc finger protein

A protein that aids in the activation and regulation of transcription, in which messenger RNA is synthesized from the DNA template; zinc finger proteins are one type of transcription factor

translation

The process of synthesizing an amino acid sequence (protein product) from the messenger RNA code

translocation

Synonym: chromosome rearrangement

A chromosome alteration in which a whole chromosome or segment of a chromosome becomes attached to or interchanged with another whole chromosome or segment, the resulting hybrid segregating together at meiosis; balanced translocations (in which there is no net loss or gain of chromosome material) are usually not associated with phenotypic abnormalities, although gene disruptions at the breakpoints of the translocation can, in some cases, cause adverse effects, including some known genetic disorders; unbalanced translocations (in which there is loss or gain of chromosome material) nearly always yield an abnormal phenotype

trinucleotide repeat

Sequences of three nucleotides repeated a number of times in tandem within a gene. Normal polymorphic variation in repeat number with no clinical significance commonly occurs between individuals. Abnormally large alleles are classified in increasing order of size as mutable normal alleles, reduced penetrance alleles, and full penetrance alleles, respectively.

Related Terms: anticipation; trinucleotide repeat testing

Image LearnMore.jpg Image CaseExample.jpg

trinucleotide repeat testing

Quantification of the number of trinucleotide repeats (sets of three nucleotides of identical sequence) in a segment of DNA

Related Terms: PCR; Southern blot; Targeted mutation analysis

Image LearnMore.jpg

trisomy

The presence of a single extra chromosome, yielding a total of three chromosomes of that particular type instead of a pair. Partial trisomy refers to the presence of an extra copy of a segment of a chromosome.

trisomy rescue

The phenomenon in which a fertilized ovum initially contains 47 chromosomes (i.e., is trisomic), but loses one of the trisomic chromosomes in the process of cell division such that the resulting daughter cells and their descendants contain 46 chromosomes, the normal number

Related Terms: aneuploidy; imprinting; post-zygotic event; trisomy; uniparental disomy; uniparental disomy study

Image DiseaseExample.jpg Image LearnMore.jpg

U

unaffected

An individual who does not manifest any symptoms of a particular condition

unequal crossing over

Mispairing and exchange of DNA between genetically similar, nonhomologous chromosome regions that results in duplication or deletion of DNA in each daughter cell

Related Terms: crossing over; deletion; duplication; gene conversion; homologous chromosomes; inversion; recombination

Image DiseaseExample.jpg Image LearnMore.jpg

uniparental disomy

Synonym: UPD

The situation in which both members of a chromosome pair or segments of a chromosome pair are inherited from one parent and neither is inherited from the other parent; uniparental disomy can result in an abnormal phenotype in some cases

Related Terms: imprinting; parent-of-origin studies; trisomy rescue; uniparental disomy study

Image LearnMore.jpg Image CaseExample.jpg

uniparental disomy study

Synonyms: UPD analysis, UPD study

Testing used to identify if specific chromosomes or chromosomal segments are maternally or paternally derived; can aid in confirming the clinical diagnosis of certain disorders for which UPD is a possible underlying etiology

Related Terms: chromosome; imprinting; parent-of-origin studies; uniparental disomy

Image LearnMore.jpg Image CaseExample.jpg

V

variable expressivity

Variation in clinical features (type and severity) of a genetic disorder between affected individuals, even within the same family

Related Terms: allelic heterogeneity; interfamilial variability; intrafamilial variability; locus heterogeneity; penetrance; pleiotropy

Image LearnMore.jpg Image CaseExample.jpg

variable number tandem repeats

Synonym: VNTR

Linear arrangement of multiple copies of short repeated DNA sequences that vary in length and are highly polymorphic, making them useful as markers in linkage analysis

W

western blot

The separation of proteins on an electrophoretic gel for identification by immunological techniques

wild-type allele

The normal, as opposed to the mutant, gene or allele

X

X-chromosome inactivation

Synonym: lyonization

In females, the phenomenon by which one X chromosome (either maternally or paternally derived) is randomly inactivated in early embryonic cells, with fixed inactivation in all descendant cells; first described by the geneticist Mary Lyon

Related Terms: lyonization; manifesting carrier; mosaicism; X-chromosome inactivation study; X-linked dominant; X-linked recessive

Image LearnMore.jpg Image CaseExample.jpg

X-chromosome inactivation study

Synonym: XCI study

Molecular genetic testing to assess the relative proportion of methylated (inactive) X chromosomes to unmethylated (active) X chromosomes; used to determine if X-chromosome inactivation is random or skewed

Related Terms: X-chromosome inactivation; X-linked recessive

Image LearnMore.jpg Image CaseExample.jpg

X-linked dominant

Describes a dominant trait or disorder caused by a mutation in a gene on the X chromosome. The phenotype is expressed in heterozygous females as well as in hemizygous males (having only one X chromosome); affected males tend to have a more severe phenotype than affected females.

Related Terms: autosomal dominant; mode of inheritance; X-linked recessive

Image LearnMore.jpg Image CaseExample.jpg

X-linked lethal

A disorder caused by a dominant mutation in a gene on the X chromosome that is observed almost exclusively in females because it is almost always lethal in males who inherit the gene mutation

X-linked recessive

A mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be expressed in males who are hemizygous for the gene mutation (i.e., they have only one X chromosome) and in females who are homozygous for the gene mutation (i.e., they have a copy of the gene mutation on each of their two X chromosomes). Carrier females who have only one copy of the mutation do not usually express the phenotype, although differences in X-chromosome inactivation can lead to varying degrees of clinical expression in carrier females

Related Terms: mode of inheritance; obligate carrier; X-chromosome inactivation; X-linked dominant

Image LearnMore.jpg Image CaseExample.jpg

Z

zygosity testing

The process through which DNA sequences are compared to assess whether individuals born from a multiple gestation (twins, triplets, etc.) are monozygotic (identical) or dizygotic (fraternal); often used to identify a suitable donor for organ transplantation or to estimate disease susceptibility risk if one sibling is affected

Copyright © 1993-2014, University of Washington, Seattle. All rights reserved.

For more information, see the GeneReviews Copyright Notice and Usage Disclaimer.

For questions regarding permissions: ude.wu@tssamda.

Bookshelf ID: NBK5191
PubReader format: click here to try

Views

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...