Huntington's Disease

Genetic Testing: family-based linkage studies

In 1983, before identification of the IT15 gene, investigators characterized DNA that is closely linked to the gene and typically inherited with it as a unit (haplotype). Known as a genetic marker, this discovery enabled researchers to map the gene to the short arm (p) of chromosome 4. This led to the development and availability of testing for HD before symptom onset (presymptomatic testing). Numerous DNA markers closely linked to the HD gene have since been identified in different families (kindreds) affected by the disease.

It is important to note that such testing, called DNA linkage analysis, detects the inheritance of DNA potentially linked to the gene as opposed to the presence of the mutated gene itself. Therefore, such testing is much less specific than the direct mutation analysis previously described. DNA linkage testing necessitates the analyses of blood samples from multiple unaffected and affected family members (preferably from two generations)—and may have only a certain degree of accuracy (e.g., depending on the population investigated). Linkage analysis is no longer used for diagnosis of HD.

For most individuals with an affected parent, identification of the IT15 gene has enabled more accurate presymptomatic testing through direct DNA analysis for HD mutations. (See Genetic testing: direct mutation analysis.)