STRUCTURAL-ANALYSIS OF THE 5'-REGION OF MOUSE AND HUMAN HUNTINGTON DISEASE GENES REVEALS CONSERVATION OF PUTATIVE PROMOTER REGION AND DINUCLEOTIDE AND TRINUCLEOTIDE POLYMORPHISMS

We have previously cloned and characterized the murine homologue of th e Huntington disease (HD) gene and shown that it maps to mouse chromos ome 5 within a region of conserved synteny with human chromosome 4p16. 3. Here we present a detailed comparison of the sequence of the putati ve promoter and the organization of the 5' genomic region of the murin e (Hdh) and human HD genes encompassing the first five exons. We show that in this region these two genes share identical exon boundaries, b ut have different-size introns. Two dinucleotide (CT) and one trinucle otide intronic polymorphism in Hdh and an intronic CA polymorphism in the HD gene were identified. Comparison of 940-bp sequence 5' to the p utative translation start site reveals a highly conserved region (78.8 % nucleotide identity) between Hdh and the HD gene from nucleotide -56 to -206 (of Hdh). Neither Hdh nor the HD gene have typical TATA or CC AAT elements, but both show one putative AP2 binding site and numerous potential Sp1 binding sites. The high sequence identity between Hdh a nd the HD gene for approximately 200 bp 5' to the putative translation start site indicates that these sequences may play a role in regulati ng expression of the Huntington disease gene. (C) 1995 Academic Press, Inc.