Genetic estimates and genome-wide association studies of antibody response in Tanzanian dairy cattle

Luis E Hernandez-Castro, Elizabeth Anne Jessie Cook, Oswald Matika, Isaac Joseph Mengele, Shabani Kiyabo Motto, Shedrack Festo Bwatota, Bibiana Zirra-Shallangwa, Ricardo Pong-Wong, James Prendergast, Raphael Mrode, Philip G. Toye, Daniel Mushumbusi Komwihangilo, Eliamoni Lyatuu, Benedict E. Karani, Getrude Nangekhe, Okeyo Ally Mwai, Gabriel Mkilema Shirima, Barend Mark de Clare Bronsvoort
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Abstract

Identifying the genetic determinants of host defence against infectious pathogens is central to enhancing disease resilience and therapeutic efficacy in livestock. Here we have taken a genome-wide association approach to identify genetic variants associated with the presence of serological markers for important infectious diseases affecting dairy cattle in smallholder farms. Assessing 668,911 single-nucleotide polymorphisms in 1977 crossbreed cattle sampled from six regions of Tanzania, we identified high levels of interregional admixture and European introgression which may increase infectious disease susceptibility relative to indigenous breeds. Heritability estimates ranged from 0.03 (SE ± 0.06) to 0.44 (SE ± 0.07) depending on the pathogen assayed. Preliminary genome scans revealed several loci associated with seropositivity to the viral diseases Rift Valley fever and bovine viral diarrhoea, the protozoan parasites Neospora caninum and Toxoplasma gondii, and the bacterial pathogens Brucella sp, Leptospira hardjo and Coxiella burnetti. The associated loci mapped to genes involved in immune defence, tumour suppression, neurological processes, and cell exocytosis. We discuss future work to clarify the cellular pathways contributing to general and taxon-specific infection responses and to advance selective breeding and therapeutic target designs.
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坦桑尼亚奶牛抗体反应的遗传估计和全基因组关联研究
确定宿主防御传染性病原体的遗传决定因素对于提高牲畜的抗病能力和治疗效果至关重要。在此,我们采用了全基因组关联方法,以确定与影响小农农场奶牛的重要传染病血清学标记物存在相关的遗传变异。通过对来自坦桑尼亚六个地区的 1977 头杂交牛的 668,911 个单核苷酸多态性进行评估,我们发现了高水平的区域间混杂和欧洲引种,这可能会增加相对于本地品种的传染病易感性。遗传率估计值从 0.03(SE ± 0.06)到 0.44(SE ± 0.07)不等,取决于所测定的病原体。初步的基因组扫描发现了几个与病毒性疾病裂谷热和牛病毒性腹泻、原生动物寄生虫犬新孢子虫和弓形虫以及细菌性病原体布鲁氏菌、钩端螺旋体和烧伤克氏菌的血清阳性相关的基因位点。相关基因座映射到涉及免疫防御、肿瘤抑制、神经过程和细胞外泌的基因。我们讨论了今后的工作,以澄清导致一般和类群特异性感染反应的细胞途径,并推进选择性育种和治疗目标的设计。
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