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

Autor(es):Mostrar menos -

Galvan, A. ^[1] ; Vorraro, F. ^[2] ; Cabrera, W. ^[2] ; Ribeiro, O. G. ^[2] ; Starobinas, N. ^[2] ; Jensen, J. R. ^[2] ; dos Santos Carneiro, P. ^[2] ; De Franco, M. ^[2] ; Gao, X. ^[3] ; Ibanez, O. C. M. ^[2] ; Dragani, T. A. ^[1]

Afiliação do(s) autor(es)

^[1] Fdn IRCCS Ist Nazl Tumori, Dept Predict & Prevent Med, I-20133 Milan - Italy

^[2] Inst Butantan, Lab Imunogenet, Sao Paulo - Brazil

^[3] Univ So Calif, Dept Ophthalmol & Prevent Med, Los Angeles, CA - USA

• Tipo de documento: Artigo Científico
• Fonte: Genes and Immunity; v. 12, n. 5, p. 390-394, JUL 2011.
• Citações Web of Science: 7

Resumo

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-1 beta) 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-1 beta 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. Genes and Immunity (2011) 12, 390-394; doi:10.1038/gene.2011.10; published online 24 February 2011 (AU)

• Processo FAPESP: 03/05486-7 - Determinação de fatores genéticos que afetam a resistência ou susceptibilidade à carcinogênese química e à intensidade da resposta inflamatória aguda, empregando modelo de linhagens de camundongos
• Beneficiário: Olga Celia Martinez Ibanez
• Modalidade de apoio: Auxílio à Pesquisa - Temático