Huntington's Disease Collaborative Research

Huntington’s disease is an autosomal dominant neurodegenerative disorder characterized by an abnormally high number of CAG repeats (polyglutamine) in the huntingtin (HTT) gene (also known as IT15), found in the short arm of chromosome 4, specifically, p16.3 (Buetow et al. 1991). Symptoms of this disorder include chorea (involuntary jerking movements), cognitive deficits, motor deficits, and changes in behavior. This disease gets progressively worse over time, starting with subtle behavioral, cognitive, and physical changes, progressing to severe memory decline, substantial personality changes, and debilitating motor and physiological deficits, and ending in death due to the incapacitating symptoms (Zuccato et al. 2010). Patients are generally
It started in 1983 when Gusella et al. mapped the HTT gene using restriction fragment length polymorphisms (RFLPs). Two families were used for the linkage analysis, an American family and a Venezuelan family, and a total of 12 DNA probes were used to detect RFLPs, one of which, G8, suggested linkage to the gene. The LOD score for this locus was 1.81 for the American family and 6.72 for the Venezuelan family with a recombination frequency (훳) of 0, suggesting that two polymorphic sites in the G8 locus are closely linked. Using somatic cell hybridization, Gusella et al. mapped the G8 sequence to chromosome 4 (1983). In 1987, Gilliam et al. used RFLPs and DNA probes to map the gene using two American families and one Venezuelan family. The LOD score of the HD gene and D4S43, a marker closely linked to another HD marker (D4S10), was 1.85 in one of the American families, 5.28 in the other American family, and 37.62 in the Venezualan family, with a recombination frequency of 0.00., thus, HD was mapped to 4p16.3, where these markers resided. MacDonald et al. (1992) ultimately mapped the genetic defect to an area between D4S182 and D4S180 of 4p16.3 using haplotype analysis of two Western European Descent