Rare Variants in Transcript and Potential Regulatory Regions Explain a Small Percentage of the Missing Heritability of Complex Traits in Cattle

The proportion of genetic variation in complex traits explained by rare variants is a key question for genomic prediction, and for identifying the basis of “missing heritability”–the proportion of additive genetic variation not captured by common variants on SNP arrays. Sequence variants in transcript and regulatory regions from 429 sequenced animals were used to impute high density SNP genotypes of 3311 Holstein sires to sequence. There were 675,062 common variants (MAF>0.05), 102,549 uncommon variants (0.01复杂性状的遗传变异中由罕见变异所解释的比例，是基因组预测以及解析"缺失遗传力（missing heritability）"本质的核心问题——缺失遗传力指的是单核苷酸多态性（Single Nucleotide Polymorphism，SNP）芯片上的常见变异无法捕获的加性遗传变异占比。本研究利用429头已测序个体的转录组与调控区域内的序列变异，对3311头荷斯坦种公牛的高密度SNP基因型进行基因型填充。该数据集共包含675062个常见变异（次要等位基因频率（Minor Allele Frequency，MAF）>0.05）、102549个少见变异（0.01<MAF）