Linkage Disequilibrium and Physical Mapping of Pas1 in Mice

  1. Giacomo Manenti1,
  2. Amanda Stafford2,
  3. Laura De Gregorio1,
  4. Manuela Gariboldi1,
  5. F. Stefania Falvella1,
  6. Philip Avner2, and
  7. Tommaso A. Dragani1,3
  1. 1Department of Experimental Oncology, Istituto Nazionale Tumori, Milan, Italy; 2Unite de Genetique Moleculaire Murine, Unite de Recherche Associe Centre National de la Recherche Scientifique (URA CNRS) 1968, Institut Pasteur, Paris, France

Abstract

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 Pas1locus, 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.

Footnotes

  • 3 Corresponding author.

  • E-MAIL dragani{at}istitutotumori.mi.it; FAX 39-02-2390642.

    • Received July 29, 1998.
    • Accepted May 26, 1999.
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