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Candidate lung tumor susceptibility genes identified through whole-genome association analyses in inbred mice.

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.

journal_name

Nat Genet

journal_title

Nature genetics

authors

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

doi

10.1038/ng1849

subject

Has Abstract

pub_date

2006-08-01 00:00:00

pages

888-95

issue

8

eissn

1061-4036

issn

1546-1718

pii

ng1849

journal_volume

38

pub_type

杂志文章

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