Genetic Control of IL-1β Production and Inflammatory Response by the Mouse <i>Irm1</i> Locus

Vorraro, Francisca; Galvan, Antonella; Cabrera, Wafa Hanna Koury; Carneiro, Patrı́cia; Ribeiro, Orlando; Franco, Marcelo De; Starobinas, Nancy; Jensen, José Ricardo; Séman, Michel; Dragani, Tommaso A.; Ibañez, Olga M.

doi:10.4049/jimmunol.1000358

Cited by 23 publications

(43 citation statements)

References 19 publications

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“…3 Using genotype data of 1064 autosomal single nucleotide polymorphisms (SNPs) in 281 (AIRmax Â AIRmin) F2 mice, we analyzed genetic clustering and computed the gap statistics, allowing up to 100 null simulations. Visual inspection of the hierarchical plot suggested that the F2 population clusters into several genetically related subgroups (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

“…This locus was not detected in a previous genetic linkage analysis of pedigrees in the same F2 mice. 3 On chromosome 7, the Irm1 locus was confirmed as linked to both infiltrating cell number and IL-1b production. In particular, for cell number phenotype, the rs13479477 SNP (P ¼ 6.3 Â 10…”

Section: à5mentioning

confidence: 99%

“…The most highly associated SNP was rs32381191 mapping at 135.56 Mb (P ¼ 1.9 Â 10 À16 , Table 3), which, together with SNP rs31680975, were also the two best statistically associated SNPs in the pedigree analysis. 3 Complex genetics of inflammatory response evidenced by SNP genetic profile The present genome-wide association analysis detected only two of the 7-11 QTLs expected in AIR lines 2 for the phenotype (number of infiltrating cells) used to select the lines and explained only a small fraction of the phenotypic variation (R 2 ¼ 7.9%, P ¼ 1.7 Â 10…”

Section: à7mentioning

confidence: 99%

“…3 For IL1b production, three markers were highly significantly associated, including the same SNP rs13479477 linked to infiltrating cell number. The most highly associated SNP was rs32381191 mapping at 135.56 Mb (P ¼ 1.9 Â 10 À16 , Table 3), which, together with SNP rs31680975, were also the two best statistically associated SNPs in the pedigree analysis.…”

Section: à7mentioning

confidence: 99%

“…2 By genetic linkage analysis of the full pedigrees of the (AIRmax Â AIRmin) F2 population, we previously mapped the major inflammatory response modulator 1 (Irm1) locus on distal chromosome 7, linked to the number of infiltrating cells through the production of interleukin 1 beta (IL-1b). 3 QTL mapping in outbred lines requires the availability of complete and fully genotyped pedigrees. Here, we explored the possibility of mapping loci that affect the complex phenotypes in non-inbred crosses even in the absence of pedigree information.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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We tested the possibility to map loci affecting the acute inflammatory response (AIR) in an (AIRmax Â 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 ¼ 6.3 Â 10 À7 ; Irm2: P ¼ 8.2 Â 10 À5) and interleukin 1 beta (IL-1b) production (Irm1: P ¼ 1.9 Â 10 À16 ; Irm2: P ¼ 1.1 Â 10 À6 ). 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 (Po3.4 Â 10 À3 ) with the number of infiltrating cells or IL-1b 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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Section: Resultsmentioning

confidence: 99%

Section: à5mentioning

confidence: 99%