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GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.—ED.
Genetics clinics, staffed by genetics professionals, provide information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.
For current information on availability of genetic testing for disorders included in this section, see GeneTests Laboratory Directory. —ED.
Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. To find a genetics or prenatal diagnosis clinic, see the GeneTests Clinic Directory.
Referring to an individual who manifests symptoms of a particular condition
One version of a gene at a given location (locus) along a chromosome
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
Synonyms: false paternity, nonpaternity
The situation in which the alleged father of a particular individual is not the biological father
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
Synonyms: sequence analysis, gene sequencing, sequencing
The process by which the nucleotide sequence is determined for the entire coding region of a gene
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
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
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
Synonyms: aGH, array GH
A method of examining multiple genes/loci simultaneously to identify genetic imbalance caused by the gain or loss of chromosomal material. Array GH may be designed as a multi-disorder (multi-gene) screening array to detect deletions/duplications across the genome or it may be designed as a targeted array GH to interrogate a specific gene or chromosome segment.
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
Refers to any of the chromosomes other than the sex-determining chromosomes (i.e., the X and Y) or the genes on these chromosomes
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)
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
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
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.
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
Synonym: polymorphism
An alteration in a gene distinct from the normal, wild-type allele that does not appear to have a deleterious effect
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
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
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.
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.
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
Synonym: open reading frame
All exons of a gene that contribute to the protein product(s) of the gene
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)
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
Synonym: CSGE
A type of mutation scanning in which a segment of DNA is screened for mismatch pairing between normal and mutated base pairs.
Present from birth, but not necessarily genetic
Genetic relatedness between individuals descended from at least one common ancestor
The individual (not necessarily affected) who presents for genetic counseling and through whom a family with an inherited disorder comes to medical attention
A constellation of findings caused by a small chromosome deletion or duplication that spans two or more adjacent genes
The inclusion of two or more linked genes on a chromosome in the same gamete leading to their transmission together
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
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
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
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.
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.
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.
The study of the structure, function, and abnormalities of human chromosomes
Synonym: copy number analysis
Testing that identifies deletions/duplications of an entire exon, multiple exons, or a whole gene that are not readily detectable by sequence analysis of genomic DNA. A variety of methods may be used including quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and targeted array GH (gene/chromosome segment-specific). A full array GH analysis that detects deletions/duplications across the genome may also include a specific gene/chromosome segment of interest. Note: Gene- or chromosome segment-array GH may be listed by disease in the GeneTests Laboratory Directory, but multi-disorder (multi-gene) screening array GH is listed only as Miscellaneous Testing.
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.
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
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.
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
The normal number of chromosomes in a somatic cell; in humans, 46 chromosomes (22 pairs of autosomes and two sex chromosomes)
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
A gene alteration that causes or predisposes an individual to a specific disease
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
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
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
A specific region or amino acid sequence in a protein associated with a particular function or corresponding segment of DNA
See autosomal dominant or X-linked dominant.
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).
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%.
An individual who is heterozygous for a mutation at each of two separate genetic loci
The clinical study of malformation syndromes
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
Any chromosome number that is a multiple of the haploid number
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
Synonyms: alternate paternity, nonpaternity
The situation in which the alleged father of a particular individual is not the biological father
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
A phenotype that occurs in more than one family member; may have genetic or non-genetic etiology
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
In a family, the sequence alteration observed that causes or predisposes to a particular disease; the mutation may be rare or common
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
Any relative who is one meiosis away from a particular individual in a family (i.e., parent, sibling, offspring)
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).
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.
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.
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.
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
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).
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
In autosomal dominant, autosomal recessive, and X-linked disorders caused by nucleotide repeat expansion, an abnormally large allele that is associated with disease manifestations
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.
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.
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)
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
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
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
The complete DNA sequence, containing all genetic information and supporting proteins, in the chromosomes of an individual or species
The cell line from which egg or sperm cells (gametes) are derived
Two or more genetic or cytogenetic cell lines confined to the precursor (germline) cells of the egg or sperm; formerly called gonadal mosaicism
See germline mosaicism.
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
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
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
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
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
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.
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
An individual who has two identical alleles at a particular locus, one on each chromosome of a pair
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
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
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
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
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
In linkage analysis, the ability to distinguish between maternally-inherited and paternally-inherited DNA markers (polymorphisms) within or near a given gene of interest
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
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
Variability in clinical presentation of a particular disorder among affected individuals from different families
Variability in clinical presentation of a particular disorder among affected individuals within the same immediate or extended family
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.
Non-coding sequence of DNA removed from mature messenger RNA prior to translation
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.
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.
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.
An abnormality that occurs in the absence of other systemic involvement
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
An extended family; term often used in linkage studies to refer to large families
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.
The tendency for genes or segments of DNA closely positioned along a chromosome to segregate together at meiosis and therefore be inherited together
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
The physical site or location of a specific gene on a chromosome
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).
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
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
Synonym: mapped phenotype
A gene or phenotype whose relative position on a segment of DNA or on a chromosome has been established
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
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.
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
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
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
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
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.
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.
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.
A single base pair substitution that results in the translation of a different amino acid at that position
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
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
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
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
Within a single individual or tissue, the occurrence of two or more cell lines with different genetic or chromosomal constitutions
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.
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.
Synonyms: sequence alteration, splicing mutation
Any alteration in a gene from its natural state; may be disease-causing or a benign, normal variant
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.
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
The likelihood that an individual with a negative test result is actually unaffected and/or does not have the particular gene mutation in question
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
A single base pair substitution that prematurely codes for a stop in amino acid translation (stop codon)
Synonym: northern blotting analysis
The separation of sequences or fragments of RNA, partially digested by endonucleases, on an electrophoretic gel
A mutation that results in either no gene product or the absence of function at the phenotypic level
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
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
An inversion in which the breakpoints are confined to one arm of a chromosome; the inverted segment does not span the centromere
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
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
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).
A diagram of the genetic relationships and medical history of a family using standard symbols and terminology
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.
An inversion in which the breakpoints occur on both arms of a chromosome. The inverted segment spans the centromere.
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.
An alteration in DNA sequence caused by a single nucleotide base change, insertion, or deletion
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).
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
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).
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
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
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)
Testing offered to asymptomatic individuals with a family history of a genetic disorder and a potential risk of eventually developing the disorder
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.
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
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.
Synonym: unique mutation
A rare disease-causing mutation observed in a few families
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)
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
One of several different testing methods that reveals either the structure or function of a particular protein product
Testing to examine the expression of a mutation in a recombinant protein to confirm its pathogenicity
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
Synonym: PTT
Means of identifying the shortened (truncated) proteins that result from mutations which specifically cause premature termination of mRNA translation
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
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
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
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
See autosomal recessive.
A segment of one chromosome is exchanged with a segment of another chromosome of a different pair
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
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
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.
Follow-up testing automatically initiated when certain test results are observed in the laboratory; used to clarify or elaborate on primary test results
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.
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.
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
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
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
The separation of the homologous chromosomes and their random distribution to the gametes at meiosis
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
Synonyms: gene sequencing, sequencing
Process by which the nucleotide sequence is determined for a segment of DNA
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)
A single occurrence of a disorder in a family
Synonym: SSCP
A type of mutation scanning; the identification of abnormally migrating single-stranded DNA segments on gel electrophoresis
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
Two or more genetic or cytogenetic cell lines within the cells of the body (may or may not include the germline cells)
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).
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
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
The chance occurrence of a disorder or abnormality that is not likely to recur in a family
Synonym: single-stranded conformational polymorphism
A type of mutation scanning; the identification of abnormally migrating single-stranded DNA segments on gel electrophoresis
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
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.
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.
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
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.
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
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
The process of synthesizing an amino acid sequence (protein product) from the messenger RNA code
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
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.
Quantification of the number of trinucleotide repeats (sets of three nucleotides of identical sequence) in a segment of DNA
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.
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
An individual who does not manifest any symptoms of a particular condition
Mispairing and exchange of DNA between genetically similar, nonhomologous chromosome regions that results in duplication or deletion of DNA in each daughter cell
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
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
Variation in clinical features (type and severity) of a genetic disorder between affected individuals, even within the same family
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
The separation of proteins on an electrophoretic gel for identification by immunological techniques
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
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
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.
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
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
