Haplotype association mapping identifies a candidate gene region in mice infected with staphylococcus aureus

Nicole V. Johnson, Sun Hee Ahn, Hitesh Deshmukh, Mikhail K. Levin, Charlotte L. Nelson, William K. Scott, Andrew Allen, Vance G. Fowler, Lindsay G. Cowell

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)693-700
Number of pages8
JournalG3: Genes, Genomes, Genetics
Volume2
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Family
  • Host genetic susceptibility
  • Infectious disease
  • Kallikrein gene

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Johnson, N. V., Ahn, S. H., Deshmukh, H., Levin, M. K., Nelson, C. L., Scott, W. K., Allen, A., Fowler, V. G., & Cowell, L. G. (2012). Haplotype association mapping identifies a candidate gene region in mice infected with staphylococcus aureus. G3: Genes, Genomes, Genetics, 2(6), 693-700. https://doi.org/10.1534/g3.112.002501