稀有变异关联分析研究进展及其在畜禽中的应用展望

Study Progress on Rare Variants Association Studies and Its Application in Livestock

在过去十年里,全基因组关联分析成功鉴定了数以千计的常见变异与常见疾病(性状)的关联。尽管如此,缺失遗传力的问题逐渐引起了广泛关注。由于GWAS的目标是鉴定常见变异与表型的关联,稀有变异成为解释缺失遗传力的一个重要答案。随着测序技术的发展,人们得以研究稀有变异与复杂疾病(性状)的关联。一系列的稀有变异关联分析(RVAS)方法被提出并应用于人类复杂疾病中,然而在畜禽上鲜有研究。本文首先综述了RVAS中具有代表性的测序核关联检验(SKAT)及其家族;其后,总结了两种在稀有变异中常用的提高效力的方法:极端表型抽样和荟萃分析;然后,探讨了使用芯片数据研究RVAS的方法:基因型填充和稀有单倍型关联分析;最后展望了稀有变异关联分析在畜禽上的应用前景。

Genome-wide association studies have identified thousands of associations between common variants and common diseases（traits）in the last decade.Despite these discoveries,the missing heritability has attracted much concerns increasingly.Rare variants have become a key answer to explain the missing heritability,because GWAS focus on identifying the associations between common variants and phenotypes.The rapid advances in DNA sequence have made it possible to identify the associations between rare variants and common diseases（traits）.A series of rare variants association analysis（RVAS）methods have been proposed and were applicated to many human diseases,however fewer investigations in livestock.In this review,we first briefly report the methods of sequence kernel association test（SKAT）and its family,which are representative.Then,we summary two methods which are used to improve the effectiveness in RVAS：extreme phenotype sampling and meta-analysis.Hereafter,we review the methods utilizing GWAS data to perform RVAS：imputation and rare haplotype associations analysis.Finally,we provide some guidelines for performing RVAS in livestock.