Genome-wide association analysis of avian resistance to Campylobacter jejuni colonization identifies risk locus spanning the CDH13 gene.
Genome-wide association analysis of avian resistance to Campylobacter jejuni colonization identifies risk locus spanning the CDH13 gene.
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DOI：
10.1534/g3.113.006031
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发表时间：
2013-05-20
期刊：
影响因子：
--
通讯作者：
Bradley DG
中科院分区：
文献类型：
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作者：
Connell S;Meade KG;Allan B;Lloyd AT;Downing T;O'Farrelly C;Bradley DG
肠病原菌空肠弯曲杆菌是世界范围内主要的健康和经济负担，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媒介，尽管禽类定植水平的变异是可遗传的，但以前没有研究确定与定植抗性相关的基因组区域。本研究通过控制种群结构，对禽肠对空肠梭菌定殖的抗性进行了全基因组关联研究，发现T-cadherin （CDH13）基因具有全基因组意义。第二个可能的风险位点也被确定在钙调蛋白（calmodulin, CALM1）附近，钙活化钙粘蛋白功能调节剂。此外，基因表达分析的mRNA测序谱显示，这两个基因的相对表达与定植抗性显著相关。先前的功能研究表明，钙粘蛋白和钙调蛋白参与空肠梭菌在体外对人肠上皮细胞的细胞内侵袭和定植。与这一发现一致，我们的分析表明，这些基因周围的变异与鸟类体内的定植抗性有关，并强调了它们作为鸟类和人类群体中控制细菌的可能靶点的潜力。
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.
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Backert S
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Wessler, Silja
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通讯作者：
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影响因子：
16.8
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