Genome-wide association mapping to candidate polymorphism resolution in the unsequenced barley genome
Genome-wide association mapping to candidate polymorphism resolution in the unsequenced barley genome
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DOI：
10.1073/pnas.1010179107
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发表时间：
2010-12-14
影响因子：
11.1
通讯作者：
O'Sullivan, Donal M.
中科院分区：
文献类型：
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作者：
Cockram, James;White, Jon;O'Sullivan, Donal M.
尽管全基因组关联（GWA）研究在人类疾病遗传学中很常见，但直到最近才应用于植物。利用近交作物大麦的 32 个表型，我们报告了 500 个具有 1,536 个 SNP 基因分型的品种的 15 个形态性状的 GWA 作图。与大多数人类 GWA 研究相反，我们观察到染色体内部和染色体之间存在高水平的连锁不平衡。尽管如此，GWA 分析还是很容易检测到高外显率的常见等位基因。为了研究将 GWA 作图与比较分析相结合以解析未测序基因组中候选多态性水平的性状的潜力，我们在包含三个基因的 140 kb 间隔内对选定的表型（花青素色素沉着）进行了精细作图。其中，对假定的花青素途径基因 HvbHLH1 进行重新测序，发现了一个缺失，导致基本螺旋-环-螺旋结构域上游出现过早终止密码子，这诊断了我们的关联和双亲定位群体中缺乏花青素。这里描述的方法可以转移到基因组资源有限的物种，为降低未测序作物中基于图谱的克隆的阈值提供了范例。
Although commonplace in human disease genetics, genome-wide association (GWA) studies have only relatively recently been applied to plants. Using 32 phenotypes in the inbreeding crop barley, we report GWA mapping of 15 morphological traits across similar to 500 cultivars genotyped with 1,536 SNPs. In contrast to the majority of human GWA studies, we observe high levels of linkage disequilibrium within and between chromosomes. Despite this, GWA analysis readily detected common alleles of high penetrance. To investigate the potential of combining GWA mapping with comparative analysis to resolve traits to candidate polymorphism level in unsequenced genomes, we fine-mapped a selected phenotype (anthocyanin pigmentation) within a 140-kb interval containing three genes. Of these, resequencing the putative anthocyanin pathway gene HvbHLH1 identified a deletion resulting in a premature stop codon upstream of the basic helix-loop-helix domain, which was diagnostic for lack of anthocyanin in our association and biparental mapping populations. The methodology described here is transferable to species with limited genomic resources, providing a paradigm for reducing the threshold of map-based cloning in unsequenced crops.