The long term goals of this project are to isolate the Huntington's disease (HD) gene, identify the most common mutation in the gene which causes the disease and, ultimately, understand at the molecular level how a mutant allele at this locus produces the neuropathology of the disease in heterozygotes. A combination of physical mapping strategies will be employed to compile a very high resolution physical map of a region of about 2.5 Mb of DNA which now appears to be the most narrowly defined location of the disease gene. This will include several approaches to rapidly isolate and map many new DNA probes throughout this segment of chromosomal band 4p16.3. Somatic cell hybrids which retain chromosomes 4 from several important recombinants with HD will be isolated and extensively characterized. This provides a means for unequivocal haplotyping of a large number of polymorphic loci which will allow a more precise locilization for the disease gene to be made. All of the DNA from the minimal physical region shown to contain the HD gene will be isolated in overlapping cosmid and YAC clones. The cloned DNA will be thoroughly examined to identify genomic sequences likely to represent transcribed regions. Full lengih cDNA clones and genomic clones representing candidates for the HD gene will be isolated and used to compare the structure, sequence and expression of these genes in normal individuals, HD heterozygotes and HD homozygotes in order to identify a specific alteration which represents the most common HD mutation. The achievement of this goal will eventually lead to an understanding of the function of the normal HD gene produce and provide insight into how the presence of a mutant gene product disorder. This information will hopefully point to possible completely prevent the onset of symptoms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025631-08
Application #
2265610
Study Section
Neurology C Study Section (NEUC)
Project Start
1991-02-01
Project End
1998-01-31
Budget Start
1995-02-01
Budget End
1996-01-31
Support Year
8
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Biochemistry
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
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