Using genomics to understand the genetic architecture of tolerance to Aleutian disease in mink

阿留申病（Aleutian disease，AD）是由水貂阿留申病病毒（Aleutian disease virus，AD）引起的一种水貂病，是影响加拿大和世界范围内水貂生产的最具经济意义的疾病。加拿大水貂生产商每年在测试和损失畜群方面的AD成本超过100万美元。感染后的临床结果包括生殖失败、生长性能降低和死亡率增加。虽然这种疾病没有疫苗或治疗方法，但由于水貂对感染的免疫反应存在变异性，因此在水貂中存在AD耐受性的遗传变异。基因组学技术为阐明疾病耐受性的生物学提供了巨大的机会，但这项技术的潜力尚未在水貂健康方面进行研究。本研究计划的目标是使用基因组学和生物信息学方法，结合免疫分析，以促进我们对水貂AD耐受性的遗传机制的理解。该研究计划将寻求（1）使用下一代测序创建水貂的第一个基因组组装，并设计用于水貂基因组学发现的稳健可靠的SNP检测，（2）发现基因组结构和选择特征，并鉴定解释AD耐受性变异的新遗传变异，以及（3）确定AD耐受性与其他重要经济性状如繁殖性能、毛皮质量、生长速度和毛皮大小的遗传关系。这项工作需要在加拿大达尔豪西农业园区的加拿大毛皮动物研究中心收集大量数据，该中心是加拿大唯一的水貂研究农场。该计划中获得的信息将有助于对水貂AD耐受性的遗传结构以及这可能如何影响水貂健康和生产力的新见解。该研究项目的结果将有助于降低加拿大水貂养殖场的AD成本。此外，这些研究的结果将用于设计和实施类似的方法，以促进我们对水貂和其他动物物种或人类疾病（如Chediak-Higashi综合征或耳聋）的其他重要疾病的了解，这些疾病在商业水貂养殖场普遍存在。该计划将产生高素质的人才，能够开发和应用创新的基因组学和生物信息学方法，用于农业和健康科学。

Aleutian disease (AD) caused by the Aleutian mink disease virus, is the most economically significant disease impacting mink (Neovison vison) production in Canada and worldwide. The costs of AD to the Canadian mink producers is over a million dollars annually in testing and loss of herds. Clinical outcomes following infection include reproductive failure, reduced growth performance and increased mortality. Although this disease has no vaccine or treatment, genetic variation in AD tolerance exists in mink due to the variability in their immune response to infection. Genomics technology provides tremendous opportunities to elucidate the biology of disease tolerance but the potential of this technology has not yet been investigated in mink health. The goals of this research program are to use genomics and bioinformatics approaches paired with analysis of immunity to advance our understanding of the genetic mechanisms underlying AD tolerance in mink. This research program will seek to (1) create the first genome assembly of mink using next generation sequencing and design a robust and reliable SNP assay for genomics discovery in mink, (2) discover genome structure and signature of selection as well as identify new genetic variants explaining variation in AD tolerance, and (3) identify the genetic relationships of AD tolerance with other economically important traits such as reproductive performance, fur quality, growth rate and pelt size. This work requires extensive data collection in the Canadian Centre for Fur Animal Research at Dalhousie Agriculture campus, which is the only mink research farm in Canada. The information gained in this program will contribute novel insights into genetic architecture of AD tolerance in mink and how this may impact mink health and productivity. The results of this research program will help to reduce the costs of AD to the Canadian mink farmers. Furthermore, results from these studies will be used to design and implement the similar methods to advance our understanding of other important diseases in mink and other animal species or human diseases such as Chediak-Higashi syndrome or deafness, which are prevalent on commercial mink farms. This program will generate highly qualified personnel capable of developing and applying innovative genomics and bioinformatics approaches of use in agriculture and the health sciences.