GLOSSARY

Allele

One version of a gene at a given location (locus) along a chromosome. Different alleles produce variation in inherited charcteristics such as hair color or blood type. In an individual, one form of allele (the dominant one) may be expressed more than another form (the recessive one). When "genes" are considered simply as segmentas of a nucleotide sequence, allele refers to each of the possible alternative nucleotides at a specific position in the sequence. For example, a CT polymorphism such as CCT[C/T]CCAT would have two alleles: C and T

Analysis of the entire coding region OR gene sequencing, sequence analysis, sequencing 

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

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) 

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) 

Background risk OR 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 

Benign variant OR polymorphism 

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

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 

Carrier testing OR carrier detection OR heterozygote testing 

Testing used to identify usually asymptomatic individuals who have a gene mutation for an autosomal recessive or X-linked recessive disorder , or who have a chromosome rearrangement (eg, translocation, inversion) 

Chromosome

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

Coding region OR open reading frame

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

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

Congenital

Present from birth, but not necessarily genetic 

De novo mutation OR de novo gene mutation OR 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

Deletion

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

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

Direct DNA analysis OR direct DNA

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

Disease-causing mutation

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

DNA OR 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 

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

Exon

Coding sequence of DNA present in mature messenger RNA

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 

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

Frameshift mutation OR out-of-frame deletion, out-of-frame mutation

An insertion 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

Gene

The basic unit of heredity, consisting of a segment ofDNA 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.

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.

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 itslocus name prior to its identification) 

Gene therapy

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

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 OR 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 afamily 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)

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

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

Heterozygote

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

Homozygote

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

Hotspot mutation region

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

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 

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

Informed consent

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

Intron

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

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. 

Locus

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

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)

Manifesting carrier

An individual who has, at a particularlocus, a recessive, disease-causing allele on one chromosome and a normalallele 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

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

Microsatellite OR 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 testing OR 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.

Mismatch repair mechanism OR 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

Molecular genetic testing OR DNA testing, DNA-based testing, molecular testing 

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

Mosaicism

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

Multifactorial inheritance OR 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

Mutation OR sequence alteration, splicing mutation

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

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

Nonsense mutation

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

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.

Parentage testing OR maternity testing, paternity 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 OR 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) 

Pedigree

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

Phenotype

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

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

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.

Population risk OR 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  

Predictive testing

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

Predisposing mutation OR 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 OR 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

Prenatal diagnosis OR 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

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 OR unique mutation

A rare disease-causing mutation observed in a few families 

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

Reading frame OR 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 

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

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

RNA OR 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) 

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

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 OR 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 OR gene sequencing, sequencing

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

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

Splicing OR 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

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

Transcription

The process of synthesizing messenger RNA (mRNA) from DNA

Translation

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

Wild-type allele

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