Haplotype Association Mapping Identifies a Candidate Gene Region in Mice Infected With Staphylococcus aureus.
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.
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https://hdl.handle.net/10161/13318Published Version (Please cite this version)
10.1534/g3.112.002501Publication Info
Johnson, Nicole V; Ahn, Sun Hee; Deshmukh, Hitesh; Levin, Mikhail K; Nelson, Charlotte
L; Scott, William K; ... Cowell, Lindsay G (2012). Haplotype Association Mapping Identifies a Candidate Gene Region in Mice Infected
With Staphylococcus aureus. G3 (Bethesda), 2(6). pp. 693-700. 10.1534/g3.112.002501. Retrieved from https://hdl.handle.net/10161/13318.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Andrew Scott Allen
Professor of Biostatistics & Bioinformatics
My research focuses on developing new statistical methods for identifying susceptibility
loci involved in complex human disease. It involves a mix of genetics, statistics,
and computer science and is motivated by the complexities of real data encountered
in collaborative disease-gene mapping projects.
Vance Garrison Fowler Jr.
Florence McAlister Distinguished Professor of Medicine
Determinants of Outcome in Patients with Staphylococcus aureus Bacteremia Antibacterial
ResistancePathogenesis of Bacterial Infections Tropical medicine/International Health
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