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Publication : Association study by genetic clustering detects multiple inflammatory response loci in non-inbred mice.

First Author  Galvan A Year  2011
Journal  Genes Immun Volume  12
Issue  5 Pages  390-4
PubMed ID  21346777 Mgi Jnum  J:236521
Mgi Id  MGI:5806338 Doi  10.1038/gene.2011.10
Citation  Galvan A, et al. (2011) Association study by genetic clustering detects multiple inflammatory response loci in non-inbred mice. Genes Immun 12(5):390-4
abstractText  We tested the possibility to map loci affecting the acute inflammatory response (AIR) in an (AIRmax x AIRmin) F2 intercross mouse population derived from non-inbred parents, by association analysis in the absence of pedigree information. Using 1064 autosomal single nucleotide polymorphisms (SNPs), we clustered the intercross population into 12 groups of genetically related individuals. Association analysis adjusted for genetic clusters allowed to identify two loci, inflammatory response modulator 1 (Irm1) on chromosome 7 previously detected by genetic linkage analysis in the F2 mice, and a new locus on chromosome 5 (Irm2), linked to the number of infiltrating cells in subcutaneous inflammatory exudates (Irm1: P=6.3 x 10(-7); Irm2: P=8.2 x 10(-5)) and interleukin 1 beta (IL-1beta) production (Irm1: P=1.9 x 10(-16); Irm2: P=1.1 x 10(-6)). Use of a polygenic model based on additive effects of the rare alleles of 15 or 18 SNPs associated at suggestive genome-wide statistical threshold (P<3.4 x 10(-3)) with the number of infiltrating cells or IL-1beta production, respectively, allowed prediction of the inflammatory response of progenitor AIR mice. Our findings suggest the usefulness of association analysis in combination with genetic clustering to map loci affecting complex phenotypes in non-inbred animal species.
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