Fine mapping and candidate gene analyses of pulmonary adenoma resistance 1, a major genetic determinant of mouse lung adenoma resistance

Cancer Res. 2007 Mar 15;67(6):2508-16. doi: 10.1158/0008-5472.CAN-06-3157.

Abstract

Pulmonary adenoma resistance 1 (Par1) is a major genetic determinant of mouse lung adenoma resistance. Although Par1 was previously mapped to mouse chromosome 11 by conventional linkage analyses, its candidate region was broad and undefined. In our present study, we generated Par1 congenic mice using two mouse strains A/J (Par1/-) and Mus spretus (Par1/+). Analyzing these congenic mice enabled us to fine map the Par1 quantitative trait loci (QTL) into a 2.0-cM (2.2 Mb) chromosomal region between genetic marker D11Mit70 and the gene Hoxb9. We then conducted systematic candidate gene screening through nucleotide polymorphism and expression analyses. Genes showing differential lung tissue expression or carrying nonsynonymous single nucleotide polymorphisms were identified and discussed. In particular, we evaluated tumor suppressor gene Tob1 for its Par1 candidacy. Our findings have narrowed the Par1 QTL region and will greatly facilitate the identification of the major genetic determinant of mouse lung adenoma resistance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoma / genetics*
  • Animals
  • Carrier Proteins / genetics
  • Chromosome Mapping
  • Female
  • Genes, Tumor Suppressor*
  • Intracellular Signaling Peptides and Proteins
  • Lung Neoplasms / genetics*
  • Male
  • Mice
  • Mice, Inbred A
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci

Substances

  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Tob1 protein, mouse