Enhancing resistance to ketosis through genomics

高产奶牛容易患酮病，这是一种代谢性疾病，对奶牛的健康、繁殖力和生产造成不利影响。酮病抗性作为一种健康性状，由于其多基因特性、表型模糊、遗传相关不利于产奶量等特点，很难在遗传上进行改良。拟议的项目旨在澄清围绕这一特征的一些不确定性，并通过基因组学提高对酮病的抵抗力。数千头奶牛将使用一种新的低密度芯片进行基因分型，该芯片包含在酮病候选基因中识别的标记。将要进行基因分型的动物已经拥有50K基因类型，这将允许将新的SNPs归因于任何已经用50K阵列进行基因分型的动物。输入数十万只动物的基因类型将极大地提高检测与酮病表型相关的能力。将对生产者记录的临床酮病和移位皱胃病例、测量的牛奶β-羟丁酸以及这些性状的去退化估计育种值进行关联分析。这些结果将在独立的人群中得到验证，并通过对最有效的SNP进行功能研究来验证。这项工作将提高我们对酮病的认识，提供基因组工具通过选择来增强抵抗力，并为被确认为酮病易感的奶牛提供有针对性的预防和治疗策略。**

High-yielding dairy cattle are susceptible to ketosis, a metabolic disease, which negatively affects the health, fertility and production of the cow. As a health trait, ketosis-resistance is difficult to improve genetically due to its polygenic nature, fuzzy phenotypes and unfavorable genetic correlation to milk production. The proposed project aims to clarify some of the uncertainty surrounding this trait and improve ketosis-resistance through genomics. Several thousand cows will be genotyped with a new, low-density chip, which contains markers that were identified in candidate genes for ketosis. The animals that will be genotyped already have 50K genotypes, which will allow for imputation of the new SNPs for any animal that has been genotyped with the 50K array. Imputing the genotypes of hundreds of thousands of animals will greatly improve the power to detect associations with ketosis phenotypes. Association analyses will be conducted for producer-recorded cases of clinical ketosis and displaced abomasum, measured milk beta-hydroxybutyrate, as well as deregressed estimated breeding values for each of these traits. These results will be validated in an independent population, as well by conducting functional studies of the most effective SNPs. This work will improve our understanding of ketosis, provide genomic tools to enhance resistance through selection and lead to targeted prevention and treatment strategies for cows identified as being susceptible to ketosis. **