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

Genes & Immunity volume 12, pages 390–394 (2011)Cite this article

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Abstract

We tested the possibility to map loci affecting the acute inflammatory response (AIR) in an (AIRmax × 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 × 10−7; Irm2: P=8.2 × 10−5) and interleukin 1 beta (IL-1β) production (Irm1: P=1.9 × 10−16; Irm2: P=1.1 × 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 × 10−3) with the number of infiltrating cells or IL-1β 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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Acknowledgements

This work was supported in part by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Grant 03/05486-7 to OCMI and by Associazione Italiana and Fondazione Italiana Ricerca Cancro (AIRC and FIRC) grants to TAD. FV was supported in part by FAPESP, OCMI and MDF by Conselho Nacional de Pesquisa (CNPq). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the paper.

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  1. O C M Ibañez and T A Dragani: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Predictive and Preventive Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy

    A Galvan & T A Dragani

  2. Laboratory of Imunogenetics, Instituto Butantan, São Paulo, Brazil

    F Vorraro, W Cabrera, O G Ribeiro, N Starobinas, J R Jensen, P dos Santos Carneiro, M De Franco & O C M Ibañez

  3. Department of Ophthalmology and Preventive Medicine, University of Southern California, Los Angeles, CA, USA

    X Gao

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  1. A Galvan
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  8. M De Franco
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  11. T A Dragani
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Correspondence to T A Dragani.

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Galvan, A., Vorraro, F., Cabrera, W. et al. Association study by genetic clustering detects multiple inflammatory response loci in non-inbred mice. Genes Immun 12, 390–394 (2011). https://doi.org/10.1038/gene.2011.10

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