The Genotyping Core is a new addition to the HD Center spawned by our successful identification of the genetic defect that causes Huntington's disease (HD). The expanded and unstable array of CAG triplet repeats at the 5' end of the IT15 gene appears to be the universal cause of the death of striatal neurons in HD. The process by which this genetic lesion kills is not known but the discovery of the mutation provides a starting point for deciphering the steps that lead to the pathology of HD. The instability of the repeat in meiotic transmission has raised numerous new questions concerning the peculiarities of the repeat's behavior and its consequences in HD families. The discovery of this unusual mutational mechanisms has also created a new parameter by which all future biochemical, anatomical and genetic studies of the HD defect may be compared and interpreted; the length of the CAG repeat. Investigations into the behavior of the repeat and the repercussions of its expression will all require knowledge of IT15 CAG repeat length. Consequently the Genotyping Core will service all Projects in this Center, providing them with information crucial to successful completion of their specific aims. The major goal of the Genotyping Core is to provide investigators in the HD Center with an accurate estimate of the lengths of the IT15 CAG repeats carried by the normal and disease chromosomes in the cells and tissues that are being studied. Measurement of allele sizes at other polymorphic sites in IT15 and at other loci in 4p16.3 will also be performed to generate useful haplotypes for ancestral analysis. We will also offer the service of typing alleles at other genetic loci that cause neurodegenerative disease, including trinucleotide repeats associated with spino-bulbar and muscular atrophy, spinocerebellar ataxia 1 and dentatorubral and pallidoluysian atrophy, and ApoE alleles associated with Alzheimer's disease. The Core will provide additional services as needed, such as culturing of cells, and the extraction of genomic DNA from cells and tissues.
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