PHYSICAL MAP OF MOUSE CHROMOSOME-17 IN THE REGION RELEVANT FOR POSITIONAL CLONING OF THE HYBRID STERILITY-1 GENE

Hybrid sterility 1 (Hst1) is the major gene responsible for sterility of male hybrids between Mus musculus and certain laboratory strains. T hus, Hst1 is of importance in studying both postreproductive isolation of closely related species and male fertility. It has been mapped to mouse chromosome 17 in the region corresponding to the third inversion of the t haplotypes. The aim of the present study was to construct a physical map of the Hst1 region as the first step in an effort to clon e the gene. Three yeast artificial chromosome (YAC) libraries (Princet on, Whitehead, and ICRF) were screened with polymerase chain reaction (PCR) oligonucleotide primers and DNA probes specific for loci previou sly mapped into the region of the third inversion. The isolated YAC cl ones were restriction mapped and arranged into contigs. Sixteen YAC cl ones were arranged into a single contig encompassing a region approxim ately 2000 kb long based on restriction mapping of highly overlapping but independently derived YAC clones. Five new loci in the region of t he third inversion were mapped and the order and approximate physical distances of 12 loci established in this contig. The Hst1 gene maps ap proximately 0.2 cM proximal to the D17Ph1 locus encompassed by the YAC contig. Since the contig extends at least 1200 kb proximal to D17Ph1, it should contain the Hst1 gene. (C) 1994 Academic Press, Inc.