GENE STRUCTURE AND MAP LOCATION OF THE MURINE HOMOLOG OF THE HUNTINGTON-ASSOCIATED PROTEIN, HAP1

Huntington's Disease (HD) is an inherited progressive neurodegenerativ e disorder associated with a mutation in a gene expressed in both affe cted and non-affected tissues. The selective neuropathology in HD is t hought to be mediated in part through interactions with other proteins including the Huntington Associated Protein, HAP-1, which is predomin antly expressed in the brain. We have mapped its murine homolog, Hap1, to mouse Chr 11 (band D), which shares extensive synteny with human C hr 17 including the region 17q21-q22, where the gene for 'frontotempor al dementia and parkinsonism linked to chromosome 17' has bee mapped. In addition, we have sequenced a 21,984 base pair (bp) genomic clone e ncompassing the entire Hap1 gene. It is organized as 11 exons and flan ked by exons from potentially one or more novel genes. At least three Hap1 transcripts (Hap1-A; Hap1-B; Hap1-C) can be formed by alternative splicing at the 3' end of the gene leading to protein isoforms with n ovel C-termini.