Analysis of runs of homozygosity from next generation sequence data in Canadian dairy cattle

牛饲养者通常通过使用系谱信息和最近的SNP数据来计算亲本亲缘关系的程度来估计近交系数。近年来，奶牛种群的近交率有所增加，随着基因组选择的加强，近交率可能会继续稳步增加。在加拿大，Stachowicz等人（2011）发现泽西岛和荷尔斯泰因种群的基因库都非常有限，并且已经受到近亲繁殖积累和遗传多样性丧失的负面影响。作者认为，随着时间的推移，通过基因组选择而迅速缩短的世代间隔将导致更快的近亲繁殖积累。他们的结论是，有必要对选择和交配决策进行管理，以控制未来的近亲繁殖。利用现有的基因组信息，我们建议使用新的基因组工具来更好地了解加拿大奶牛种群的近交机制，并重新评估适当的近交率。本研究项目分为三个阶段：(1)利用阵列和序列信息对加拿大奶牛品种的基因组近交进行分析，并对纯合子位点区域进行特征描述，包括纯合子区域内有害变异和中性变异的发生率和功能严重程度；(2)利用所鉴定的纯合子区域进行全基因组关联分析，了解基因组近交的后果；(3)基于模拟结果将新知识整合到选择策略中，以帮助管理基因组近交。我们认为，现有的基因组信息为监测和控制有害隐性等位基因和单倍型的频率提供了新的可能性。**

Cattle breeders commonly estimate inbreeding coefficients by calculating the degree of parental relatedness using pedigree information, and, more recently, SNP data. The rate of inbreeding in dairy cattle populations has increased in recent years, and will likely continue to increase steadily as genomic selection intensifies. In Canada, Stachowicz et al. (2011) found that both Jersey and Holstein populations have very limited gene pools and already suffer from negative effects of accumulation of inbreeding and genetic diversity loss. The authors suggest that the rapid decrease in generation interval through genomic selection will cause an even faster accumulation of inbreeding over time. They concluded that a need exists for managing selection and mating decisions to control future inbreeding. Using current genomic information, we propose the use of new genomic tools to better understand the mechanisms of inbreeding in Canadian dairy populations and to re-evaluate appropriate rates of inbreeding. This research project involves 3 stages: (1) analysis of genomic inbreeding in Canadian dairy breeds using both array and sequence information, and characterisation of regions of homozygous loci, including rate and functional severity of deleterious and neutral variants within runs of homozygosity, (2) understanding the consequences of genomic inbreeding through genome-wide association analyses using the regions of homozygosity identified, (3) integration of new knowledge into selection strategies to help manage genomic inbreeding based on simulation results. We propose that the currently available genomic information provides new possibilities for monitoring and controlling the frequency of deleterious recessive alleles and haplotypes. **