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QTL Variant Detail
QTL variant: Why1MOLF/EiJ
Name: wild-derived hyperresponse 1; MOLF/EiJ
MGI ID: MGI:3773873
QTL: Why1  Location: unknown  Genetic Position: Chr6, Syntenic
Strain of Specimen:  MOLF/EiJ
Allele Type:    QTL
Mutation:    Undefined
    This allele confers increased Toll-like receptor-mediated cytokine response compared to C57BL/6J. (J:131437)
View phenotypes and curated references for all genotypes (concatenated display).
Why1 and Why2 engage in epistatic interactions.

Mapping and Phenotype information for this QTL, its variants and associated markers


Linkage analysis was performed on 82 C57BL/6J x (C57BL/6J x MOLF/EiJ)F1 backcross animals to identify QTLs associated with Toll-like receptor (TLR) mediated cytokine production. IL-6 production after stimulation of macrophages with lipoteichoic acid (LTA) was assessed as a measure of TLR-mediated cytokine responsiveness.

Significant linkage to cytokine response mapped to 49 cM on mouse Chromosome 6 near D6Mit328 (LOD=3.69). This locus is named Why1 (wild-derived hyperresponse 1). The MOLF/EiJ-derived allele confersincreased IL-6 production (cytokine response) after LTA stimulation. Irak2 (49.5 cM) is a potential candidate gene for Why1. Several polymorphisms exist between the Irak2 gene sequences of C57BL/6J and MOLF/EiJ. However, these polymorphisms do not appearto correlate with the phenotype.

Why2 (wild-derived hyperresponse 2) mapped to 41 cM on mouse Chromosome 9 near D9Mit155 (LOD=5.49). This locus appears to act negatively with MOLF/EiJ-derived alleles conferring decreased IL-6 production. The QTL interval spans 23 cM. Microarray analysis identified Irak1bp1 as a potential candidate gene displaying 20-fold expression difference between C57BL/6J and MOLF/EiJ. Northern blot analysis showed increased Irak1bp1 expression in MOLF/EiJ macrophages after LTA stimulation compared to C57BL/6J macrophages.

Why1 (chr6) and Why2 (chr9) exhibit significant epistatic interaction (LRS=48.1). Authors hypothesize Why2 evolved as a negative regulator of the pro-inflammatory effects of Why1.

Original:  J:131437 Conner JR, et al., Forward genetic analysis of Toll-like receptor responses in wild-derived mice reveals a novel antiinflammatory role for IRAK1BP1. J Exp Med. 2008 Feb 18;205(2):305-14
All:  3 reference(s)

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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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