ational behavior (1). The gene mutation responsible for Huntington=s disease has been located on chromosome 4, and a carrier of the disease carries the defective gene one of their two copies of the chromosome. DNA testing can be used to determine if a person has inherited the Huntington=s disease gene because the DNA next to the Huntington=s disease gene on the parent=s abnormal chromosome 4 is different from the corresponding segment DNA on the Parent=s normal chromosome.
Huntington=s chorea is an autosomal dominant neurodegenerative disorder caused when the widely expressed Huntington protein contains an expanded glutamine (CAG) repeat which is expressed as a polyglutamine tract near the N-terminus of the gene product, Huntington (2,9). This leads to selective degeneration and neuronal morphological abnormalities which may be due to interactions between Huntington and other proteins to which it binds, such as the Huntington=s associated protein (HAP1). The biological significance of this association is not yet clear because neither Huntington nor HAP1 have significant homology to known proteins. Also, mutant Huntington is expressed throughout the brain, so its involvement in selective cell death is unclear. There is a preferential loss of neurons in the striatum and cortex in Huntington=s patients(4).
Larger polyglutamine expansions in Huntington are associated with earlier onset and increased severity of the disease (4).
Two pathogenic processes have been suggested as the basis for neurodegeneration in Huntington=s disease. One process involves interaction of mutant Huntington with other proteins producing a change in their function. The other is that Huntington might homodimerize or heterodimerize to build large, poorly soluble protein aggregates.
N-terminal Huntington fragments form intranuclear aggregates in Huntington=s disease patients, and these aggregates may be involved in the pathogenesis of ...