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

TitleFine mapping and candidate gene analyses of pulmonary adenoma resistance 1, a major genetic determinant of mouse lung adenoma resistance.
Publication TypeJournal Article
Year of Publication2007
AuthorsWang, M, Zhang, Z, Zhang, Z, Vikis, H, Yan, Y, Wang, Y, You, M
JournalCancer Res
Volume67
Issue6
Pagination2508-16
Date Published2007 Mar 15
ISSN0008-5472
KeywordsAdenoma, Animals, Carrier Proteins, Chromosome Mapping, Female, Genes, Tumor Suppressor, Lung Neoplasms, Male, Mice, Mice, Inbred A, Polymorphism, Single Nucleotide, Quantitative Trait Loci
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.

DOI10.1158/0008-5472.CAN-06-3157
Alternate JournalCancer Res.
PubMed ID17363568
Grant ListCA099147 / CA / NCI NIH HHS / United States
CA099187 / CA / NCI NIH HHS / United States
ES012063 / ES / NIEHS NIH HHS / United States
ES013340 / ES / NIEHS NIH HHS / United States