College of Animal Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
Hubei Key Laboratory of Animal Embryo and Molecular Breeding, Institute of Animal Husbandry and Veterinary, Hubei Provincial Academy of Agricultural Sciences, Wuhan, 430064, China.
Sci Rep. 2022 Jul 25;12(1):12645. doi: 10.1038/s41598-022-15851-x.
Pigs not only function as a major meat source worldwide but also are commonly used as an animal model for studying human complex traits. A large haplotype reference panel has been used to facilitate efficient phasing and imputation of relatively sparse genome-wide microarray chips and low-coverage sequencing data. Using the imputed genotypes in the downstream analysis, such as GWASs, TWASs, eQTL mapping and genomic prediction (GS), is beneficial for obtaining novel findings. However, currently, there is still a lack of publicly available and high-quality pig reference panels with large sample sizes and high diversity, which greatly limits the application of genotype imputation in pigs. In response, we built the pig Haplotype Reference Panel (PHARP) database. PHARP provides a reference panel of 2012 pig haplotypes at 34 million SNPs constructed using whole-genome sequence data from more than 49 studies of 71 pig breeds. It also provides Web-based analytical tools that allow researchers to carry out phasing and imputation consistently and efficiently. PHARP is freely accessible at http://alphaindex.zju.edu.cn/PHARP/index.php . We demonstrate its applicability for pig commercial 50 K SNP arrays, by accurately imputing 2.6 billion genotypes at a concordance rate value of 0.971 in 81 Large White pigs (~ 17 × sequencing coverage). We also applied our reference panel to impute the low-density SNP chip into the high-density data for three GWASs and found novel significantly associated SNPs that might be casual variants.
猪不仅是全球主要的肉类来源，还常被用作研究人类复杂性状的动物模型。大型单倍型参考面板已被用于促进相对稀疏的全基因组微阵列芯片和低覆盖度测序数据的高效相位和推断。在下游分析中使用推断的基因型，如 GWAS、TWAS、eQTL 图谱和基因组预测（GS），有利于获得新的发现。然而，目前仍然缺乏具有大样本量和高度多样性的公开可用的高质量猪参考面板，这极大地限制了基因型推断在猪中的应用。针对这一问题，我们构建了猪单倍型参考面板（PHARP）数据库。PHARP 提供了一个由 3400 万个 SNP 组成的 2012 个猪单倍型参考面板，这些 SNP 是使用来自 71 个猪品种的 49 多项研究的全基因组序列数据构建的。它还提供了基于网络的分析工具，允许研究人员一致、高效地进行相位推断。PHARP 可在 http://alphaindex.zju.edu.cn/PHARP/index.php 免费访问。我们通过在 81 头大约克夏猪中准确推断出 26 亿个基因型（一致性率为 0.971），证明了其在猪商业 50 K SNP 芯片上的适用性（约 17 倍测序覆盖率）。我们还将我们的参考面板应用于将低密度 SNP 芯片推断为三个 GWAS 的高密度数据，并发现了可能是因果变异的新的显著相关 SNP。
