Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada.
St. George's University, True Blue, Grenada.
Immunogenetics. 2018 Aug;70(8):533-546. doi: 10.1007/s00251-018-1061-7. Epub 2018 May 10.
Infectious diseases are a significant issue in animal production systems, including both the dairy and beef cattle industries. Understanding and defining the genetics of infectious disease susceptibility in cattle is an important step in the mitigation of their impact. Collagenous lectins are soluble pattern recognition receptors that form an important part of the innate immune system, which serves as the first line of host defense against pathogens. Polymorphisms in the collagenous lectin genes have been shown in previous studies to contribute to infectious disease susceptibility, and in cattle, mutations in two collagenous lectin genes (MBL1 and MBL2) are associated with mastitis. To further characterize the contribution of variation in the bovine collagenous lectins to infectious disease susceptibility, we used a pooled NGS approach to identify short nucleotide variants (SNVs) in the collagenous lectins (and regulatory DNA) of cattle with (n = 80) and without (n = 40) infectious disease. Allele frequency analysis identified 74 variants that were significantly (p < 5 × 10) associated with infectious disease, the majority of which were clustered in a 29-kb segment upstream of the collectin locus on chromosome 28. In silico analysis of the functional effects of all the variants predicted 11 SNVs with a deleterious effect on protein structure and/or function, 148 SNVs that occurred within potential transcription factor binding sites, and 31 SNVs occurring within potential miRNA binding elements. This study provides a detailed look at the genetic variation of the bovine collagenous lectins and identifies potential genetic markers for infectious disease susceptibility.
传染病是动物生产系统中的一个重大问题，包括奶牛和肉牛产业。了解和定义牛对传染病易感性的遗传基础是减轻其影响的重要步骤。胶原凝集素是可溶性模式识别受体，是先天免疫系统的重要组成部分，先天免疫系统是宿主防御病原体的第一道防线。先前的研究表明，胶原凝集素基因的多态性与传染病易感性有关，在牛中，两个胶原凝集素基因（MBL1 和 MBL2）的突变与乳腺炎有关。为了进一步表征牛胶原凝集素变异对传染病易感性的贡献，我们使用汇集的 NGS 方法来鉴定患有（n=80）和不患有（n=40）传染病的牛的胶原凝集素（和调节 DNA）中的短核苷酸变异（SNVs）。等位基因频率分析确定了 74 个与传染病显著相关（p<5×10）的变体，其中大多数聚集在 28 号染色体上凝集素基因座上游的 29-kb 片段中。所有变体的功能影响的计算机分析预测了 11 个对蛋白质结构和/或功能具有有害影响的 SNVs，148 个 SNVs 发生在潜在转录因子结合位点内，31 个 SNVs 发生在潜在 miRNA 结合元件内。本研究详细研究了牛胶原凝集素的遗传变异，并确定了传染病易感性的潜在遗传标记。
