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Vol. 9, Issue 7, 639-646, July 1999

LETTER
Linkage Disequilibrium and Physical Mapping of Pas1 in Mice

Giacomo Manenti,1 Amanda Stafford,2 Laura De Gregorio,1 Manuela Gariboldi,1 F. Stefania Falvella,1 Philip Avner,2 and Tommaso A. Dragani1,3

1 Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy; 2 Unite de Genetique Moleculaire Murine, Unite de Recherche Associe Centre National de la Recherche Scientifique (URA CNRS) 1968, Institut Pasteur, Paris, France

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 ~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 Pas1s susceptibility allele is shared by several mouse-inbred strains of independent origin, which show either high or intermediate predisposition to lung tumorigenesis. Therefore, the Pas1s 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.

3   Corresponding author.

9:639-646 ©1999 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/99 $5.00
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