title: Fine mapping and candidate gene analyses of pulmonary adenoma resistance 1, a major genetic determinant of mouse lung adenoma resistance.
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.
authors.affiliation: Department of Surgery and The Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Haris
authors.initials: H
authors.lastname: Vikis
authors.forename: Ying
authors.initials: Y
authors.lastname: Yan
authors.forename: Yian
authors.initials: Y
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: You
mesh_terms: D000236:Adenoma / Q000235:genetics*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D005260:Female; D016147:Genes, Tumor Suppressor; D047908:Intracellular Signaling Peptides and Proteins; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C490903:Tob1 protein, mouse