Version May 2024
| Term | Definition |
| Allele | A genetic locus or the genotype (base sequence) at a specific genetic locus. When used to refer to pathogenic variants, biallelic refers to a pathogenic variant affecting both alleles (homozygous for the same pathogenic variant at both alleles, or compound heterozygous with a different pathogenic variant at each allele). Monoallelic refers to a genotype affecting only one allele (heterozygous). |
| Autosomal dominant | Pattern of inheritance that requires only one affected variant allele (a variant inherited from one parent or that arises de novo) to transmit the trait or risk of disease. Not sex-linked. First-degree relatives (siblings, children) have a 50% chance of sharing (or inheriting) the variant allele. |
| Autosomal recessive | Pattern of inheritance that generally requires variants on both alleles (one from each parent) in order to transmit the trait or risk of disease. Not sex-linked. Individuals with one variant are sometimes called carriers. |
| Carrier | Individual who has a specific variant in one allele of the gene in their germline DNA (inherited from one parent or arising de novo). For recessive disorders, refers to a heterozygote who is generally (or mostly) unaffected. For dominant disorders, carriers are generally considered at risk for the disorder. |
| Compound heterozygote | Also called "double heterozygote"; refers to an individual who is heterozygous for two different variants of the same gene, one from each parent. Typically refers to pathogenic variants. |
| Expressivity | Differences in the severity of disease manifestations in individuals who share the same genotype (eg, cystic fibrosis is said to have variable expressivity because two individuals with the same genotype may have differences in the degree of pancreatic or lung dysfunction). |
| Genotyping | Determining the DNA sequence of a particular gene or portion of a gene in an individual. Can be done on DNA from sources such as nucleated epithelial cells from saliva, tumor cells from a biopsy, or WBCs from peripheral blood. Can be used to determine germline or somatic sequence, depending on the source of the cells. |
| Germline | Derived from the gametes (sperm or egg cells) and present in the early embryo; germline variants are typically present in all body cells and do not change. Germline variants can be passed down to subsequent generations. |
| Heterozygous | Having a genetic variant on one, but not both, of a pair of genes. |
| Homozygous | Having the same genetic sequence or the same allele on both chromosomes. A person can be homozygous for a pathogenic variant or for the wildtype allele. |
| Mosaicism | Having two populations of genetically distinct cells that arose from a single fertilized egg. Mosaicism that arises later during embryonic development affects a smaller proportion of cells and a more limited number of cell lineages. Individuals with mosaicism can only transmit a genetic variant to the next generation if it is present in the gametes. If an individual with mosaicism for a disease trait harbors the associated variant in the germline, the trait may present as a new finding in children who inherit the variant. |
| Mutation | Term that may be used to describe changes in DNA or protein sequence compared with a reference sequence. The American College of Genetics and Genomics (ACMG) has expressed concern that this term can cause confusion or incorrect assumptions regarding pathogenicity, and the ACMG recommends that findings from genetic testing be described using the term "variant" with a qualifier regarding pathogenicity (or lack thereof). |
| Pathogenicity | Likelihood that a specific variant is capable of causing disease or conferring disease risk. Does not determine the likelihood that disease will occur (which depends on other factors such as disease penetrance). Refer to separate table in UpToDate for the categories. |
| Pedigree | Diagram of a family showing relationships among family members, sex of each family member, presence or absence of one or more genetic disorders, and often the age at which they manifested. Used in genetic counseling to identify possible inherited causes of disease and their inheritance patterns. |
| Penetrance | Likelihood that a person with a disease-associated variant will manifest one or more features of the disease. Many disease variants have incomplete or variable penetrance, meaning that not all individuals with the variant will manifest the associated disorder. |
| Somatic | Referring to tissues that are not within the germline. Variation that arises in somatic tissues is not passed from parent to offspring. Somatic mutations are common in cancer. |
| Variant | Change in the sequence of DNA compared with a reference sequence. Variants can be benign (associated with normal gene function), pathogenic (associated with altered gene function and/or clinical disease), or of uncertain significance (VUS). Two other categories are "likely pathogenic" and "likely benign." The term polymorphism is often (but not exclusively) used for benign variants. Refer to a separate table in UpToDate that defines the categories. |
| VUS | Variant of uncertain significance (or unknown significance). Refers to a variant for which insufficient information is available to classify as benign or pathogenic. |
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