Data from: Dissecting genome-wide association signals for loss-of-function phenotypes in sorghum flavonoid pigmentation traits

Genome-wide association studies (GWAS) are a powerful method to dissect the genetic basis of traits, though in practice the effects of complex genetic architecture and population structure remain poorly understood. To compare mapping strategies we dissect the genetic control of flavonoid pigmentation traits in the cereal grass sorghum using high-resolution genotyping-by-sequencing (GBS) SNP markers. Studying the grain tannin trait, we find that General Linear Models (GLM) are not able to precisely map tan1-a, a known loss-of-function allele of the Tannin1 gene, with either a small panel (n = 142) or large association panel (n = 336), and that indirect associations limit the mapping of the Tannin1 locus to Mb-resolution. A GLM that accounts for population structure (Q) or standard Mixed Linear Model (MLM) that accounts for kinship (K) can identify tan1-a, while compressed MLMs performs worse than the naive GLM. Interestingly, a simple loss-of-function genome scan, for genotype-phenotype covariation only in the putative loss-of-function allele, is able to precisely identify the Tannin1 gene without considering relatedness. We also find that the tan1-a allele can be mapped with gene resolution in a biparental recombinant inbred line (RIL) family (n = 263) using GBS markers, but lower precision in the mapping of vegetative pigmentation traits suggest that consistent gene-level resolution will likely require larger families or multiple RILs. These findings highlight that complex association signals can emerge from even the simplest traits given epistasis and structured alleles, but that gene-resolution mapping of these traits is possible with high marker density and appropriate models.全基因组关联分析（Genome-wide association studies, GWAS）是解析性状遗传基础的有力工具，但在实际应用中，复杂遗传架构与群体结构所带来的影响仍未得到充分阐释。为对比不同定位策略，本研究利用高分辨率测序分型（genotyping-by-sequencing, GBS）单核苷酸多态性（single nucleotide polymorphism, SNP）标记，解析禾谷类作物高粱类黄酮色素沉着性状的遗传调控机制。针对籽粒单宁性状开展研究，我们发现，无论是使用小型关联群体（n=142）还是大型关联群体（n=336），一般线性模型（General Linear Models, GLM）均无法精准定位已知的Tannin1基因功能丧失等位基因tan1-a，且间接关联信号会将Tannin1位点的定位精度限制在Mb级别。考虑群体结构的一般线性模型（Q模型）或考虑亲缘关系的标准混合线性模型（Mixed Linear Model, MLM，K模型）均可识别tan1-a等位基因，而压缩混合线性模型的定位效果则劣于原始一般线性模型。有趣的是，仅针对推定功能丧失等位基因开展基因型-表型共分离分析的简易功能丧失全基因组扫描方法，无需考虑亲缘关系即可精准定位Tannin1基因。我们还发现，在双亲亲本重组自交系（recombinant inbred line, RIL）群体（n=263）中，利用GBS标记可将tan1-a等位基因定位至基因分辨率水平，但营养器官色素沉着性状的定位精度较低，这表明要实现稳定的基因级定位，可能需要更大规模的群体或多个RIL群体。本研究结果表明，即便对于最简单的性状，上位性与等位基因结构也可能产生复杂的关联信号，但借助高密度分子标记与合适的分析模型，即可实现此类性状的基因级定位。