Glossary of genetic testing terms

• Allele — A variant form of a gene found at a specific locus on a chromosome. Alleles differ in nucleotide sequence due to mutation and can be inherited across generations.

• Allelic diversity — The existence of multiple alleles at a single gene locus within a population, contributing to genetic variation.

• Amino acids — The fundamental building blocks of proteins. In humans, 20 standard amino acids are encoded by triplets (codons) in DNA via transcription and translation.

• Analyte — A substance measured in a laboratory test, such as a gene, mutation, or biomarker.

• Analytical sensitivity — The probability that a test will detect an analyte when it is present.

• Analytical specificity — The probability that a test will yield a negative result when the analyte is absent.

• Anonymization — The process of removing all identifiers from a biological sample or data such that it cannot be traced back to an individual.

• Autosomal — Refers to any of the 22 numbered (non-sex) chromosomes and the genes located on them.

• Blind testing — A quality control method using unknown samples to evaluate laboratory testing accuracy, without the technician knowing the sample's expected outcome.

• Carrier — An individual possessing one copy of a recessive allele associated with a genetic disorder who typically shows no symptoms but can pass the allele to offspring.

• Chromosome — A DNA-protein structure found in the nucleus of cells that contains the organism's genetic material.

• Clinical sensitivity — The probability that a test will be positive in individuals with a specific condition.

• Clinical specificity — The probability that a test will be negative in individuals without the condition.

• DNA (Deoxyribonucleic acid) — The hereditary material in humans and almost all other organisms, composed of sequences of nucleotides.

• Dominant — A mode of inheritance in which a trait is expressed when only one copy of the allele is present.

• Enzyme — A protein that accelerates biochemical reactions without being consumed.

• Gene / Gene locus — A segment of DNA located at a specific site (locus) on a chromosome that encodes a functional product, usually a protein.

• Gene product — The biochemical material, either RNA or protein, resulting from expression of a gene.

• Genetic heterogeneity — A phenomenon where different genetic mutations cause the same phenotype. Includes locus heterogeneity and allelic heterogeneity.

• Genetic predisposition / Genetic susceptibility — The increased likelihood of developing a particular disease due to a person's genetic makeup.

• Genome — The complete set of genes or genetic material present in a cell or organism.

• Genotype — The set of alleles an individual has at a particular gene locus, or across all loci.

• Heterozygote — An individual who has inherited two different alleles at a gene locus.

• Home brew — Laboratory-developed reagents or tests not manufactured for general distribution or sale.

• Homozygote — An individual who has inherited the same allele from both parents at a gene locus.

• Locus heterogeneity — A single disorder caused by mutations in different gene loci, e.g., breast cancer susceptibility due to mutations in BRCA1 or BRCA2.

• Mendelian inheritance — Patterns of inheritance that follow Gregor Mendel's laws, including autosomal dominant, autosomal recessive, and X-linked inheritance.

• mRNA (Messenger RNA) — The intermediary between DNA and protein synthesis, created during transcription.

• Metabolite — A chemical compound resulting from metabolism; its levels can indicate enzyme function or dysfunction.

• Mutation — Any permanent alteration in the DNA sequence, potentially causing disease or variation.

• Nucleotide — The building block of DNA and RNA, comprising a base (A, T, C, G), a sugar, and a phosphate group.

• Off-label use — Usage of an FDA-approved drug or device in a way not specified in its official labeling.

• Penetrance — The extent to which a genotype is expressed in the phenotype. Complete penetrance means 100% expression; incomplete penetrance means less than 100%.

• Phenotype — Observable physical or biochemical characteristics of an individual resulting from both genetic and environmental factors.

• Polymorphism — A genetic variant that appears in at least 1% of the population and may or may not have clinical consequences.

• Positive predictive value (PPV) — The probability that a person with a positive test result truly has the condition.

• Predisposition test — A genetic test that identifies individuals at higher risk of developing a disease due to inherited genetic variations.

• Presymptomatic test — A genetic test to determine whether an individual will develop a disorder in the future, typically when penetrance is complete.

• Proficiency testing — External assessment of a laboratory’s performance using blinded samples from an independent source.

• Protein — A biological macromolecule composed of one or more chains of amino acids and encoded by genes.

• Recombinant DNA technology — A set of molecular tools used to manipulate DNA sequences and insert them into host organisms for cloning or protein expression.

• Recessive — A trait that is only expressed when two copies of a disease-causing allele are present (homozygous or compound heterozygous).

• Sensitivity (diagnostic test) — A test's ability to correctly identify those with the condition (true positive rate).

• Specificity (diagnostic test) — A test's ability to correctly identify those without the condition (true negative rate).

• Single-gene disorder — Also known as a Mendelian disorder; caused by mutations in a single gene, often inherited in a dominant or recessive manner.

• Somatic mutation — A genetic alteration acquired by a cell after conception that is not inherited but can lead to diseases like cancer.

• Validity — The degree to which a test accurately and reliably measures the trait or condition it purports to detect. Includes both analytical and clinical validity.

• X-linked — A gene located on the X chromosome. Disorders linked to this chromosome follow specific inheritance patterns, particularly affecting males.

Additional Terms

• Copy number variation (CNV) — A segment of DNA in which copy number differences have been found among individuals and may affect disease risk or traits.

• Epigenetics — The study of heritable changes in gene expression that do not involve changes to the underlying DNA sequence.

• Exome sequencing — Sequencing of the exons (coding regions) of all known genes in the genome.

• Next-generation sequencing (NGS) — High-throughput DNA sequencing technologies that allow rapid sequencing of large amounts of DNA.

• Variants of uncertain significance (VUS) — Genetic variants whose impact on disease risk is not clearly understood.

• Zygosity — The degree of similarity between the alleles at a specific gene locus (e.g., homozygous, heterozygous).

• Germline mutation — A genetic alteration in the reproductive cells that can be passed on to offspring.

• Genome-wide association study (GWAS) — An approach that involves rapidly scanning markers across genomes of many individuals to find genetic variations associated with a particular disease.