YAC CONTIGS OF THE RAB1 AND WOBBLER (WR) SPINAL MUSCULAR-ATROPHY GENEREGION ON PROXIMAL MOUSE CHROMOSOME-11 AND OF THE HOMOLOGOUS REGION ON HUMAN-CHROMOSOME 2P

Despite rapid progress in the physical characterization of murine and human genomes, little molecular information is available on certain re gions, e.g., proximal mouse chromosome 11 (Chr 11) and human chromosom e 2p (Chr 2p). We have localized the wobbler spinal atrophy gene wr to proximal mouse Chr 11, tightly linked to Rab1, a gene coding for a sm all GTP-binding protein, and Glns-ps1, an intronless pseudogene of the glutamine synthetase gene. We have now used these markers to construc t a 1.3-Mb yeast artificial chromosome (YAC) contig of the Rab1 region on mouse Chr 11. Four YAC clones isolated from two independent YAC li braries were characterized by rare-cutting analysis, fluorescence in s itu hybridization (FISH), and sequence-tagged site (STS) isolation and mapping, Rab1 and Glns-ps1 were found to be only 200 kb apart. A pote ntial CpG island near a methylated NarI site and a trapped exon, ETG1. 1, were found between these loci, and a new STS, AHY1.1, was found ove r 250 kb from Rab1. Two overlapping YACs were identified that containe d a 150-kb region of human Chr 2p, comprising the RABI locus, AHY1.1, and the human homologue of ETG1.1, indicating a high degree of conserv ation of this region in the two species. We mapped AHY1.1 and thus hum an RABI on Chr 2p13.4-p14 using somatic cell hybrids and a radiation h ybrid panel, thus extending a known region of conserved synteny betwee n mouse Chr 11 and human Chr 2p. Recently, the gene LMGMD2B for a huma n recessive neuromuscular disease, limb girdle muscular dystrophy type 2B, has been mapped to 2p13-p16. The conservation between the mouse R ab1 and human RABI regions will be helpful in identifying candidate ge nes for the wobbler spinal muscular atrophy and in clarifying a possib le relationship between zur and LMGMD2B. (C) 1996 Academic Press, Inc.