Enhancing resistance to ketosis through genomics

高产奶牛易患酮病，这是一种代谢性疾病，对奶牛的健康、生育力和生产产生负面影响。抗酮病性状是一种健康性状，由于其多基因性、表型模糊性和与产奶量的不利遗传相关性，难以通过遗传途径进行改良。该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酮症抗性。几千头奶牛将使用一种新的低密度芯片进行基因分型，该芯片包含在酮症候选基因中鉴定的标记。将进行基因分型的动物已经具有50 K基因型，这将允许对已经用50 K阵列进行基因分型的任何动物的新SNP进行插补。对数十万动物的基因型进行估算将大大提高检测与酮症表型相关性的能力。将对生产者记录的临床酮症和皱胃移位病例、测得的乳汁β-羟基丁酸盐以及这些性状中每一个的回归估计育种值进行关联分析。这些结果将在一个独立的人群中进行验证，并通过对最有效的SNP进行功能研究。这项工作将提高我们对酮病的理解，提供基因组工具，通过选择增强抵抗力，并为被确定为易患酮病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.