mouse genome-wide association mapping needs linkage analysis to avoid false-positive loci小鼠全基因组关联映射需要避免假阳性位点连锁分析.pdfVIP

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mouse genome-wide association mapping needs linkage analysis to avoid false-positive loci小鼠全基因组关联映射需要避免假阳性位点连锁分析.pdf

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mouse genome-wide association mapping needs linkage analysis to avoid false-positive loci小鼠全基因组关联映射需要避免假阳性位点连锁分析

Mouse Genome-Wide Association Mapping Needs Linkage Analysis to Avoid False-Positive Loci 1 1 1 1 2 2 Giacomo Manenti , Antonella Galvan , Angela Pettinicchio , Gaia Trincucci , Elena Spada , Anna Zolin , 2 3 1 Silvano Milani , Anna Gonzalez-Neira , Tommaso A. Dragani * 1 Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, 2 Istituto di Statistica Medica e Biometria ‘‘GA ` Maccacaro’’, Universita di Milano, Milan, Italy, 3 Genotyping Unit (CeGen), CNIO, Madrid, Spain Abstract We carried out genome-wide association (GWA) studies in inbred mouse strains characterized for their lung tumor susceptibility phenotypes (spontaneous or urethane-induced) with panels of 12,959 (13K) or 138,793 (140K) single- nucleotide polymorphisms (SNPs). Above the statistical thresholds, we detected only SNP rs3681853 on Chromosome 5, two SNPs in the pulmonary adenoma susceptibility 1 (Pas1) locus, and SNP rs4174648 on Chromosome 16 for spontaneous tumor incidence, urethane-induced tumor incidence, and urethane-induced tumor multiplicity, respectively, with the 13K SNP panel, but only the Pas1 locus with the 140K SNP panel. Haplotype analysis carried out in the latter panel detected four additional loci. Loci reported in previous GWA studies failed to replicate. Genome-wide genetic linkage analysis in urethane- treated (BALB/c 6C3H/He)F2, (BALB/c 6SWR/J)F2, and (A/J 6C3H/He)F2 mice showed that Pas1, but none of the other loci detected previously or herein by GWA, had a significant eff