Understanding the genomic basis of health, efficiency, productivity and welfare of farm animals

家畜育种者通常通过使用系谱信息计算亲本相关程度来估计近交系数，最近，使用单核苷酸多态性（SNP）数据。近几年来，牲畜种群的近亲繁殖率有所增加，并且随着基因组选择的加强-这是强烈的定向选择的不可避免的结果-可能会继续稳步增加。本研究计划的总体目标是使用阵列数据和下一代序列数据来了解和管理加拿大牲畜纯合性运行的表型和基因型变异性，以提高动物的稳健性并管理近亲繁殖的潜在有害影响。 我们建议使用新的基因组工具，以更好地了解在加拿大牲畜种群的近亲繁殖的机制，并重新评估适当的近亲繁殖率。 首先，在考虑重组基因座的情况下，将鉴定导致阵列数据和下一代全基因组序列数据的纯合性运行的染色体区段的模式和长度，包括起源不平衡的方面（即，一种单倍型被传递的可能性高于另一种单倍型）。其次，将鉴定纯合区域的比率和功能有害（或有利）的严重性。第三，将确定全基因组关联研究纯合性和遗传染色体片段的运行影响各种经济重要性的加拿大乳品业的性状。最后，观察到的加拿大荷斯坦牛的染色体遗传特征将用于测试各种选择方案，并通过创建软件工具来帮助管理近亲繁殖，将基因组近亲繁殖的新知识融入交配策略。我们建议，目前可用的基因组信息提供了新的可能性，监测和控制有害的隐性等位基因和单倍型的频率。 本研究的最终目标是利用遗传学和基因组学方法改善农场动物的健康和福利，以及揭示家畜表型和基因型之间的关系。了解在DNA序列水平上如何控制理想和不理想的性状，有可能将健康、抗病动物的育种速度提高几个数量级。该计划开发的工具和方法不仅能够改善动物健康和福利，减少乳制品和家禽生产中的抗生素使用，而且还将专门设计用于其他牲畜物种。我希望我们开发的基因组工具将得到广泛采用，并用于选择健康的动物，这些动物具有高水平的适应性，能够获得商业成功，需要更少的抗生素，并具有更高的生活质量。

Livestock breeders commonly estimate inbreeding coefficients by calculating the degree of parental relatedness using pedigree information, and, more recently, using single nucleotide polymorphism (SNP) data. The rate of inbreeding in livestock populations has increased in recent years, and will likely continue to increase steadily as genomic selection intensifies - an unavoidable consequence of intense directional selection. The overall objective of this research program is to understand and manage the phenotypic and genotypic variability of runs of homozygosity in Canadian livestock using both array data and next-generation sequence data in order to improve animal robustness and manage the potential detrimental effects of inbreeding. We propose the use of new genomic tools to better understand the mechanisms of inbreeding in Canadian livestock populations and to re-evaluate appropriate rates of inbreeding. Firstly, patterns and lengths of chromosomal segments leading to runs of homozygosity with both array data and next-generation whole-genome sequence data under consideration of recombination loci will be identified, including aspects of origin disequilibrium (i.e. the likelihood of one haplotype being transmitted being higher than that of the other). Secondly,  the rate and functional deleterious (or advantageous) severity of homozygous regions will be identified. Thirdly, genome-wide association studies on runs of homozygosity and inherited chromosomal segments affecting various traits of economic importance to the Canadian dairy industry will be identified. Finally, the observed characteristics of chromosomal inheritance in Canadian Holsteins will be used to test various selection scenarios and to integrate new knowledge of genomic inbreeding into mating strategies by creating software tools to help manage inbreeding. We propose that currently available genomic information provides new possibilities for monitoring and controlling the frequency of deleterious recessive alleles and haplotypes.  The ultimate goal of this research is to improve health and welfare of farm animals using genetic and genomic methods, as well as to uncover the relationship between phenotype and genotype in livestock. Understanding how desirable and undesirable traits are controlled at the DNA sequence level has the potential to accelerate the breeding of healthy, disease-resistant animals by several orders of magnitude. The tools and methods developed within this program will not only be able to improve animal health and welfare, reduce antibiotic use in dairy and poultry production, but they will also be specifically designed to be transferable to other livestock species. My hope is that the genomic tools we develop will gain widespread adoption and be used to select healthy animals with high levels of fitness that attain commercial success, require less antibiotics, and have a higher quality of life.