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和最近使用单核苷酸多态(SNP)数据来计算亲缘关系的程度来估计近亲繁殖系数。近年来，家畜种群的近亲交配率有所增加，随着基因组选择的加强，近亲交配率可能会继续稳步增加--这是密集定向选择不可避免的结果。该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家畜纯合序列的表型和基因变异性，以提高动物的健壮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来更好地了解加拿大牲畜种群的近亲繁殖机制，并重新评估适当的近亲交配率。首先，将识别导致与考虑重组基因座的阵列数据和下一代全基因组序列数据的纯合性的染色体片段的模式和长度，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，将确定纯合子区域的比率和功能有害(或有利)严重程度。第三，将确定对影响加拿大乳制品行业经济重要性的各种性状的纯合性和遗传染色体片段的全基因组关联研究。最后，观察到的加拿大荷斯坦牛的染色体遗传特征将被用来测试各种选择方案，并通过创建帮助管理近亲繁殖的软件工具，将基因组近亲繁殖的新知识整合到交配策略中。我们认为，现有的基因组信息为监测和控制有害的隐性等位基因和单倍型的频率提供了新的可能性。本研究的最终目标是利用遗传和基因组方法改善家畜的健康和福利，并揭示家畜表型和基因型之间的关系。了解如何在DNA序列水平上控制可取和不可取的特征，有可能加速培育健康、抗病的动物几个数量级。在该计划内开发的工具和方法不仅能够改善动物的健康和福利，减少乳制品和家禽生产中抗生素的使用，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，并被用于选择健康的动物，这些动物具有高水平的适应性，获得商业成功，需要较少的抗生素，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.