Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin, Ireland.
G3 (Bethesda). 2013 May 20;3(5):881-90. doi: 10.1534/g3.113.006031.
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.
肠道病原体空肠弯曲菌是一个全球性的主要健康和经济负担，是细菌性胃肠炎的主要原因之一，通常与感染后自身免疫性疾病的发病有关。鸡是人类感染的主要载体，尽管禽群定植水平的变异具有遗传性，但以前的研究尚未确定与定植抗性相关的基因组区域。我们通过控制群体结构，对禽类肠道中弯曲菌定植的抗性进行了全基因组关联研究，发现了一个跨越 T-钙粘蛋白（CDH13）基因的具有全基因组意义的风险位点。还在钙调蛋白（CALM1）附近确定了第二个可能的风险位点，钙调蛋白是钙激活的钙粘蛋白功能调节剂。此外，对 mRNA 测序图谱的基因表达分析表明，这两个基因的相对表达与定植抗性显著相关。以前的功能研究表明，钙粘蛋白和钙调蛋白参与了空肠弯曲菌在体外的细胞内入侵和人类肠道上皮细胞的定植。与这一发现一致的是，我们的分析表明，这些基因周围的变异与体内禽类定植抗性有关，并强调了它们作为控制禽群和人群中细菌的潜在目标的可能性。
