title: Genome-wide association analysis of avian resistance to Campylobacter jejuni colonization identifies risk locus spanning the CDH13 gene.
abstract: The enteropathogen Campylobacter jejuni is a major worldwide health and economic burden, being one of the leading causes of bacterial gastroenteritis and commonly linked to postinfectious onset of autoimmune disease. Chickens are a major vector for human infection and even though variation in avian colonization level is heritable, no previous studies have identified regions of the genome associated with colonization resistance. We performed a genome-wide association study of resistance to C. jejuni colonization in the avian intestine by controlling for population structure, which revealed a risk locus with genome-wide significance spanning the T-cadherin (CDH13) gene. A second possible risk locus was also identified close to calmodulin (CALM1), a calcium-activated modulator of cadherin function. In addition, gene expression analysis of mRNA sequencing profiles revealed that the relative expression of the two genes is significantly associated with colonization resistance. Functional studies have previously demonstrated involvement of cadherins and calmodulin in C. jejuni intracellular invasion and colonization of human intestinal epithelial cells in vitro. Consistent with this finding, our analysis reveals that variation surrounding these genes is associated with avian colonization resistance in vivo and highlights their potential as possible targets for control of the bacterium in avian and human populations.
authors.affiliation: Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin, Ireland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Connell
authors.forename: Kieran G
authors.initials: KG
authors.lastname: Meade
authors.forename: Brenda
authors.initials: B
authors.lastname: Allan
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Lloyd
authors.forename: Tim
authors.initials: T
authors.lastname: Downing
authors.forename: Cliona
authors.initials: C
authors.lastname: O'Farrelly
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bradley
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism; D002169:Campylobacter Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*; D016123:Campylobacter jejuni / Q000254:growth & development*; D002645:Chickens / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D015169:Colony Count, Microbial; D060467:Disease Resistance / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D011201:Poultry Diseases / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D025341:Principal Component Analysis; D012307:Risk Factors
chemical_list: D015820:Cadherins; D002147:Calmodulin; C099972:H-cadherin
keywords: GWAS; cadherin; calmodulin; epithelial cell invasion; immunity; intestinal homeostasis
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