基于单倍型肉牛屠宰性状全基因组关联分析研究

doi:10.11843/j.issn.0366-6964.2022.12.010

摘要/Abstract

摘要： 单倍型标记与数量性状基因座(quantitative trait loci，QTL)之间具有较强的连锁不平衡(linkage disequilibrium，LD)关系，在基因定位和因果突变鉴定方面具有较高的应用价值。为了评估单倍型标记在基因组研究中的作用，本研究在华西牛资源群体中，选取该群体于2008—2021年间屠宰的共计1 478头平均月龄为24个月的个体进行研究，其中公牛1 333头，母牛145头。利用770K高密度芯片数据，基于LD阈值(r²>0.3)及固定单核苷酸多态(single nucleotide polymorphism,SNP)个数(5个连续SNP)两种方法进行单倍型构建，分别采用单位点SNP标记和两种单倍型标记共3种标记，基于GCTA的混合线性模型(mixed linear model,MLM)，开展宰前活重(LW)和屠宰率(DP)等屠宰性状的全基因组关联分析(genome-wide association study，GWAS)，定位影响屠宰性状的显著(P<0.05) SNPs、单倍型块和候选基因，同时比较3种标记的GWAS结果，评估3种标记的优劣。结果显示，3种标记在全基因组范围内共找到16个的显著SNPs及单倍型区域，主要分布于1、5、6、14、16、17和28号染色体上，同时鉴定到FAM184B、PPM1K、LCORL、RIMS2等10个与屠宰性状相关的候选基因，其中，基于SNP标记方法鉴定到的3个候选基因，在利用基于单倍型标记的方法中也鉴定到，且单倍型鉴定到的显著性位点或区域大多位于基因内部。在两种单倍型构建方法中，与基于固定SNP个数构建单倍型进行GWAS相比，基于LD阈值的构建方法鉴定到了更多候选基因。本研究结果表明，以单倍型开展GWAS可以综合考虑SNP位点间连锁关系，能较好地揭示复杂性状的遗传结构。

关键词: 肉牛, 单倍型, 单核苷酸多态性, 全基因组关联分析, 连锁不平衡

Abstract: Haplotypes have a stronger linkage disequilibrium (LD) relationship with quantitative trait loci (QTLs). Haplotypes tend to have higher application value in gene mapping and searching for causal mutations. In order to evaluate the role of haplotype markers in genome studies, a total of 1 478 individuals in Huaxi cattle with an average age of 24 months, including 1 333 bulls and 145 cows, were slaughtered from 2008 to 2021. The LD thresholds was set at r²>0.3 and the number of fixed-SNPs was 5 for haploblock construction with 770K chip data, GWAS using GCTA with mixed linear model based on SNP and haplotype (a total of 3 markers were used: SNP marker and two types of haplotype marker) were performed on Huaxi cattle to detect the significant SNPs, haploblocks and candidate genes associated with LW and DP traits. In addition, the GWAS results of the 3 markers were compared to evaluate the advantages and disadvantages of the 3 markers. The results showed that 16 significant SNPs and haploblocks were detected in the whole genome, mainly distributed on chromosome 1, 5, 6, 14, 16, 17 and 28. A total of 10 candidate genes, such as FAM184B,PPM1K,LCORL,RIMS2 were identified, which significantly associated with the slaughter traits. And 3 candidate genes identified by SNP markers could also be identified by haplotype method, most of the significant loci or regions identified by haplotype were located within the gene. Among the two haplotype construction methods, the LD-based construction method identified more candidate genes than the one based on the fixed-SNPs for GWAS. In this study, the results showed that haplotype-based GWAS can comprehensively consider the LD between SNPs and can better reveal the genetic structure of complex traits.

Key words: beef cattle, haplotype, SNP, genome-wide association study, linkage disequilibrium

中图分类号:

S823.2

李宏伟, 徐凌洋, 王泽昭, 蔡文涛, 朱波, 陈燕, 高雪, 张路培, 高会江, 李俊雅. 基于单倍型肉牛屠宰性状全基因组关联分析研究[J]. 畜牧兽医学报, 2022, 53(12): 4232-4243.

LI Hongwei, XU Lingyang, WANG Zezhao, CAI Wentao, ZHU Bo, CHEN Yan, GAO Xue, ZHANG Lupei, GAO Huijiang, LI Junya. Genome-wide Association Study of Slaughter Traits Based on Haplotype in Beef Cattle[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(12): 4232-4243.

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