Linkage disequilibrium and physical mapping of Pas1 in mice

By using linkage disequilibrium (LD) analysis in 21 strains of known suscep tibility to lung cancer and by assembling a YAC contig, we mapped to a simi lar to 1.5-Mb region on distal mouse chromosome 6 the Pasl locus, the major determinant of lung cancer predisposition in mice. Our results, on the bas is of haplotype and phenetic analysis, suggest that the Pasl(s) susceptibil ity allele is shared by several mouse-inbred strains of independent origin, which show either high or intermediate predisposition to lung tumorigenesi s. Therefore, the Pasl(s) allele is probably derived from an ancestral mous e rather than from independent mutations of the same gene. We showed the fe asibility of LD in common inbred strains for the fine mapping of disease lo ci, and provided the biological basis and the reagents for the cloning of t he Pasl gene.