Haplotype Association Mapping Identifies a Candidate Gene Region in Mice Infected With Staphylococcus aureus.

Published

Journal Article

Exposure to Staphylococcus aureus has a variety of outcomes, from asymptomatic colonization to fatal infection. Strong evidence suggests that host genetics play an important role in susceptibility, but the specific host genetic factors involved are not known. The availability of genome-wide single nucleotide polymorphism (SNP) data for inbred Mus musculus strains means that haplotype association mapping can be used to identify candidate susceptibility genes. We applied haplotype association mapping to Perlegen SNP data and kidney bacterial counts from Staphylococcus aureus-infected mice from 13 inbred strains and detected an associated block on chromosome 7. Strong experimental evidence supports the result: a separate study demonstrated the presence of a susceptibility locus on chromosome 7 using consomic mice. The associated block contains no genes, but lies within the gene cluster of the 26-member extended kallikrein gene family, whose members have well-recognized roles in the generation of antimicrobial peptides and the regulation of inflammation. Efficient mixed-model association (EMMA) testing of all SNPs with two alleles and located within the gene cluster boundaries finds two significant associations: one of the three polymorphisms defining the associated block and one in the gene closest to the block, Klk1b11. In addition, we find that 7 of the 26 kallikrein genes are differentially expressed between susceptible and resistant mice, including the Klk1b11 gene. These genes represent a promising set of candidate genes influencing susceptibility to Staphylococcus aureus.

Full Text

Duke Authors

Cited Authors

  • Johnson, NV; Ahn, SH; Deshmukh, H; Levin, MK; Nelson, CL; Scott, WK; Allen, A; Fowler, VG; Cowell, LG

Published Date

  • June 2012

Published In

Volume / Issue

  • 2 / 6

Start / End Page

  • 693 - 700

PubMed ID

  • 22690378

Pubmed Central ID

  • 22690378

Electronic International Standard Serial Number (EISSN)

  • 2160-1836

Digital Object Identifier (DOI)

  • 10.1534/g3.112.002501

Language

  • eng

Conference Location

  • United States