HUMAN HOMOLOG OF A MOUSE SEQUENCE FROM THE DYSTONIA MUSCULORUM LOCUS IS ON CHROMOSOME 6P12

Dystonia musculorum is a hereditary neurodegenerative disease in mice that affects sensory neurons. In an effort to clone the gene responsib le for this disorder, we have assembled a genomic contig spanning 75 k b of the dystonia musculorum (dt) locus. Within this genomic contig, w e have identified a small restriction fragment that shows evolutionary conservation to rat, hamster, rabbit, and human genomic DNA. Using th is mouse sequence, we have cloned the conserved human genomic fragment . Sequence analysis of the mouse and human genomic fragments revealed that they share a sequence similarity of 82% over 175 bp. A panel of h uman/rodent somatic cell hybrids was used to map the human genomic seq uence to Chromosome (Chr) 6, and high-resolution in situ hybridization (FISH) allowed it to be sublocalized to 6p12. The human homolog of th e mouse Bpag1 gene, a gene tightly linked to the mouse dt gene, also m aps to Chr 6. Thus, this comparative mapping reveals a new region of c onserved synteny between the chromosomes of mouse and human. Mapping t he human homolog of the mouse dr gene enables us to initiate linkage s tudies to identify neurodegenerative disorders that may be caused by m utations in this gene.