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

Pengyuan Liu, Yian Wang, Haris Vikis, Anna Maciag, Daolong Wang, Yan Lu, Yan Liu, Ming You

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

We performed a whole-genome association analysis of lung tumor susceptibility using dense SNP maps (∼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.

Original languageEnglish (US)
Pages (from-to)888-895
Number of pages8
JournalNature Genetics
Volume38
Issue number8
DOIs
StatePublished - Aug 2006

ASJC Scopus subject areas

  • Genetics

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