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Promoting Safe and Effective Genetic Testing in the United States


Allele — The actual nucleotide sequence of a gene on a chromosome. Changes in sequence from one allele to another arise as a result of mutation in the germline and can be transmitted to the next generation.

Allelic diversity — Within populations, the presence of different alleles at a gene locus.

Amino acids — The building blocks of proteins. In vertebrates, there are 20 amino acids. In a gene, each amino acid is encoded by a sequence of 3 nucleotides (triplet) that instructs the cell to insert that amino acid in a specific position as the protein is assembled. No triplet encodes for more than one amino acid but different triplets encode for the same amino acid.

Analyte — The substance measured by a laboratory test, for instance, a specific mutation or allele.

Analytical sensitivity, specificitySee Sensitivity, Specificity

Anonymization — Removing all identifiers from a specimen without retaining any code. Consequently, there is no way the specimen can be traced back to the person from which it came.

Autosomal — A gene (or its alleles) on one of the 22 autosomes. See Chromosome

Blind testing — Use of a specimen whose contents are unknown to the laboratory, or to the laboratory technician, to assess the ability of the laboratory to perform a test correctly. Usually the technician is aware that the specimen is being used for quality assessment but does not know (i.e., is blind to) its contents. In the most rigorous blinding, the specimen arrives at the laboratoryas a routine specimen.

Carrier — (1) A person of either gender who has inherited a disease-causing autosomal allele from one parent and a normal allele from the other parent. Inheritants of disease-causing alleles from both parents results in an autosomal recessive disease. (2) A female who possesses an allele on one of her X chromosomes (X-linked) which results in disease in males. In most cases, carriers suffer no ill effects from possession of the allele. "Heterozygote" for autosomal recessive or X-linked disorders is a synonym for "carrier." (3) A person who has inherited a single allele which results in an autosomal dominant disease.

Chromosome — The rod-like nucleoproteins along which the genes are arrayed in the nucleus. In human somatic cells, the chromosomes consist of 22 pairs of autosomes and, in females, two X chromosomes and, in males an X chromosome and a Y chromosome. Normally, therefore, each cell contains 46 chromosomes.

Clinical sensitivity, specificity — See Sensitivity, Specificity

DNA — Deoxyribonucleic acid. A linear sequence of deoxyribonucleotides (nucleotides for short). See Nucleotide.

Dominant — A condition that is manifest in heterozygotes.

Enzyme — A protein with a catalytic function (i.e., one that accelerates a chemical reaction reaching equilibrium).

Gene, gene locus — The position on a chromosome at which alleles reside. Alleles are transcribed into mRNA.

Gene product — The mRNA or protein encoded by a specific gene, or more properly, alleles of the gene.

Genetic heterogeneity — (1) The presence of different alleles at a gene locus. See Allelic diversity. (2) The ability of more than one allele to cause the same trait, for instance, a disease. Alleles at different gene loci (locus heterogeneity), as well as those at the same locus (allelic diversity), may each be expressed as the same trait.

Genetic predisposition or susceptibility — A genotype that increases the risk of disease but does not make it certain. The susceptibility-conferring allele will be inherited in Mendelian fashion but the disease itself will not. The single locus genotype is insufficient to result in disease. Impaired expression of alleles at other gene loci and/or environmental factors are needed before disease appears.

Genome — The entire array of genes of an organism or species.

Genotype — (1) The alleles that an individual possesses at a gene locus. One of these alleles is inherited from the mother, the other from the father. (2) An individual's entire array of single locus genotypes.

Heterozygote — A person who has inherited two different alleles (one from each parent) at a gene locus. Usually interpreted to mean that one of the alleles is expressed normally. See Carrier.

Home brew — Reagents or the combination of reagents made in a laboratory, or purchased reagents used by that laboratory for clinical tests and not for sale to other laboratories.

Homozygote — A person who has inherited identical alleles (one from each parent) at a gene locus.

Locus heterogeneity — Alleles at different gene loci each capable of causing or increasing susceptibility to a disease, for example, alleles at both the BRCA1 and BRCA2 locus can increase susceptibility to breast cancer.

Mendelian — See Single gene (Mendelian) disorder

mRNA — Messenger RNA. The ribonucleic acid (RNA) transcribed from the DNA of a gene in the cell nucleus. mRNA is the template from which proteins are translated.

Metabolite — Usually a low molecular weight compound that is either used in or produced by an enzyme-catalyzed reaction. If the enzyme is dysfunctional, a metabolite used by the reaction it catalyzes will accumulate, whereas a metabolite formed as a result of the reaction will be absent or reduced in concentration. Mutation — Any change in the nucleotide sequence of DNA.

Nucleotide — The basic unit of DNA, consisting of adenine, cytosine, guanine or thymine, and deoxyribose, and phosphate.

Off label — The use of an FDA-approved drug or device for a purpose other than that intended by the manufacturer and described on the label. FDA only approves drugs or devices for their intended use as described on the label.

Penetrance — The characteristic phenotypic effect of a genotype. If the phenotype is always expressed in the presence of the genotype, the genotype is completely penetrant. If it is not always expressed, it is incompletely penetrant.

Phenotype — The biochemical, physiological, and physical characteristics resulting from the interaction of genotype with environment.

Polymorphism — Frequently occurring variation in a nucleotide sequence. Polymorphisms in genes result in protein polymorphisms. A polymorphism is said to occur when the most common allele has a frequency of no greater than 99 percent. Some forms of some polymorphisms are associated with increased risk of disease.

Positive predictive value (PPV) — The probability that a person with a positive test result has, or will get, the disease for which the analyte is used as a predictor.

Predisposition test — A test for a genetic predisposition (incompletely penetrant conditions). Not all people with a positive test result will manifest the disease during their lifetimes.

Presymptomatic test — A test for a completely penetrant single-gene disease.

Proficiency testing — The use of blind testing to assess whether the laboratory can perform a test correctly. Usually the samples are provided by an organization independent of the laboratories performing the test.

Protein — String of amino acids linked by peptide bonds. Some proteins have more than one polypeptide chain. Each chain is encoded by a different gene.

Recombinant DNA techniques — The ability to excise exact segments of DNA and insert them into DNA of other organisms, which can then replicate the segment millions of times.

Recessive — A condition that is expressed in homozygotes or in compound heterozygotes (i.e., those who have inherited a different disease-related allele (at the same gene locus) from each parent).


  • Analytical — The probability that a test will detect an analyte when it is present in a specimen.
  • Clinical — The probability that a person with a disease, or who will get a disease, will have a positive test result.

Single gene (Mendelian) disorder — The presence of an allele in either single dose (dominant disorders in males or females, X-linked disorders in males), or double dose (recessive disorders), accounts for the presence of disease. The inheritance of these disorders follow the ratios first described by Gregor Mendel.

Somatic mutation — A mutation in the DNA of any cell in the body (somatic cells), except those in the germline.


  • Analytical — The probability that a test will be negative when an analyte is absent from a specimen.
  • Clinical — The probability that a test will be negative in a person free of a disease, and who will not get the disease.

Validity, analytic or clinical — See Positive predictive value, Sensitivity, and Specificity

X-linked — A gene on the X chromosome.

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Last updated: April 01, 2006