Linkage disequilibrium and physical mapping of Pas1 in mice.
By using linkage disequilibrium (LD) analysis in 21 strains of known susceptibility to lung cancer and by assembling a YAC contig, we mapped to a approximately 1.5-Mb region on distal mouse chromosome 6 the Pas1 locus, the major determinant of lung cancer predisposition in mice. Our results, on the basis of haplotype and phenetic analysis, suggest that the Pas1(s) susceptibility allele is shared by several mouse-inbred strains of independent origin, which show either high or intermediate predisposition to lung tumorigenesis. Therefore, the Pas1(s) allele is probably derived from an ancestral mouse rather than from independent mutations of the same gene. We showed the feasibility of LD in common inbred strains for the fine mapping of disease loci, and provided the biological basis and the reagents for the cloning of the Pas1 gene.
Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy.
G
G
Manenti
A
A
Stafford
L
L
De Gregorio
M
M
Gariboldi
F S
FS
Falvella
P
P
Avner
T A
TA
Dragani
D000236:Adenoma / Q000235:genetics*; D000818:Animals; D002875:Chromosomes / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D015810:Linkage Disequilibrium; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009115:Muridae; D010802:Phylogeny; D020161:Physical Chromosome Mapping
D005819:Genetic Markers