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Candidate lung tumor susceptibility genes identified through whole-genome association analyses in inbred mice. Nat Genet 2006 Aug;38(8):888-95

Date

07/25/2006

Pubmed ID

16862160

DOI

10.1038/ng1849

Scopus ID

2-s2.0-33746556713   65 Citations

Abstract

We performed a whole-genome association analysis of lung tumor susceptibility using dense SNP maps ( approximately 1 SNP per 20 kb) in inbred mice. We reproduced the pulmonary adenoma susceptibility 1 (Pas1) locus identified in previous linkage studies and further narrowed this quantitative trait locus (QTL) to a region of less than 0.5 Mb in which at least two genes, Kras2 (Kirsten rat sarcoma oncogene 2) and Casc1 (cancer susceptibility candidate 1; also known as Las1), are strong candidates. Casc1 knockout mouse tumor bioassays showed that Casc1-deficient mice were susceptible to chemical induction of lung tumors. We also found three more genetic loci for lung adenoma development. Analysis of one of these candidate loci identified a previously uncharacterized gene Lasc1, bearing a nonsynonymous substitution (D102E). We found that the Lasc1 Glu102 allele preferentially promotes lung tumor cell growth. Our findings demonstrate the prospects for using dense SNP maps in laboratory mice to refine previous QTL regions and identify genetic determinants of complex traits.

Author List

Liu P, Wang Y, Vikis H, Maciag A, Wang D, Lu Y, Liu Y, You M

Authors

Pengyuan Liu PhD Adjunct Professor in the Physiology department at Medical College of Wisconsin
Yian Wang MD, PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Ming You MD, PhD Associate Provost, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenoma
Alleles
Animals
Chromosome Mapping
Genetic Predisposition to Disease
Genome
Humans
Lung Neoplasms
Mice
Mice, Inbred Strains
Mice, Knockout
Polymorphism, Single Nucleotide
Quantitative Trait Loci
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d