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Genome-wide association analysis of avian resistance to Campylobacter jejuni colonization identifies risk locus spanning the CDH13 gene

Connell, Sarah, Meade, Kieran G., Allan, Brenda, Lloyd, Andrew T., Downing, Tim, O'Farrelly, Cliona and Bradley, Daniel G. (2013) Genome-wide association analysis of avian resistance to Campylobacter jejuni colonization identifies risk locus spanning the CDH13 gene. G3, 3 (5). pp. 881-890. ISSN 2160-1836

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 genomewide 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.
Metadata
Item Type:Article (Published)
Refereed:Yes
Uncontrolled Keywords:GWAS; Intestinal homeostasis; Epithelial cell invasion; Cadherin; Calmodulin; Immunity
Subjects:Biological Sciences > Genetics
Biological Sciences > Bioinformatics
Biological Sciences > Immunology
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Biotechnology
Publisher:Genetics Society of America
Official URL:http://dx.doi.org/10.1534/g3.113.006031
Copyright Information:© 2013 The Authors
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 License. View License
ID Code:21051
Deposited On:27 Jan 2016 12:07 by Tim Downing . Last Modified 19 Jul 2018 15:07
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