Combining GWAS and TWAS to identify candidate causal genes for tocochromanol levels in maize grain

IF 3.3 3区 生物学 Genetics Pub Date : 2022-04-03 DOI:10.1093/genetics/iyac091
Di Wu, Xiaowei Li, Ryokei Tanaka, Joshua C. Wood, Laura E. Tibbs-Cortes, M. Magallanes-Lundback, Nolan Bornowski, J. Hamilton, Brieanne Vaillancourt, C. Diepenbrock, Xianran Li, Nicholas T. Deason, Gregory R. Schoenbaum, Jianming Yu, C. Robin Buell, D. DellaPenna, M. Gore
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引用次数: 11

Abstract

Tocochromanols (tocopherols and tocotrienols, collectively vitamin E) are lipid-soluble antioxidants important for both plant fitness and human health. The main dietary sources of vitamin E are seed oils that often accumulate high levels of tocopherol isoforms with lower vitamin E activity. The tocochromanol biosynthetic pathway is conserved across plant species but an integrated view of the genes and mechanisms underlying natural variation of tocochromanol levels in seed of most cereal crops remains limited. To address this issue, we utilized the high mapping resolution of the maize Ames panel of ∼1,500 inbred lines scored with 12.2 million single-nucleotide polymorphisms to generate metabolomic (mature grain tocochromanols) and transcriptomic (developing grain) data sets for genetic mapping. By combining results from genome- and transcriptome-wide association studies, we identified a total of 13 candidate causal gene loci, including five that had not been previously associated with maize grain tocochromanols: four biosynthetic genes (arodeH2 paralog, dxs1, vte5, and vte7) and a plastid S-adenosyl methionine transporter (samt1). Expression quantitative trait locus (eQTL) mapping of these 13 gene loci revealed that they are predominantly regulated by cis-eQTL. Through a joint statistical analysis, we implicated cis-acting variants as responsible for co-localized eQTL and GWAS association signals. Our multi-omics approach provided increased statistical power and mapping resolution to enable a detailed characterization of the genetic and regulatory architecture underlying tocochromanol accumulation in maize grain and provided insights for ongoing biofortification efforts to breed and/or engineer vitamin E and antioxidant levels in maize and other cereals.
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结合GWAS和TWAS鉴定玉米粒中生育酚水平的候选致病基因
生育酚(生育酚和生育三烯酚,统称维生素E)是脂溶性抗氧化剂,对植物健康和人类健康都很重要。维生素E的主要膳食来源是种子油,种子油通常积累高水平的生育酚异构体,而维生素E活性较低。生育酚生物合成途径在植物物种中是保守的,但对大多数谷物作物种子中生育酚水平自然变化的基因和机制的综合看法仍然有限。为了解决这个问题,我们利用玉米Ames小组的高作图分辨率,用1220万个单核苷酸多态性对约1500个自交系进行评分,生成用于遗传作图的代谢组学(成熟谷物生育酚)和转录组学(发育中的谷物)数据集。通过结合全基因组和转录组关联研究的结果,我们共确定了13个候选致病基因位点,其中5个先前未与玉米粒生育酚相关:4个生物合成基因(arodeH2 paralog、dxs1、vte5和vte7)和一个质体S-腺苷甲硫氨酸转运蛋白(samt1)。这13个基因位点的表达定量性状位点(eQTL)定位表明,它们主要受顺式eQTL的调控。通过联合统计分析,我们推测顺式作用变异体负责共同定位的eQTL和GWAS关联信号。我们的多组学方法提供了更高的统计能力和绘图分辨率,从而能够详细表征玉米籽粒中生育酚积累的遗传和调控结构,并为正在进行的生物强化工作提供了见解,以培育和/或设计玉米和其他谷物中的维生素E和抗氧化剂水平。
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来源期刊
Genetics
Genetics 生物-遗传学
CiteScore
6.20
自引率
6.10%
发文量
177
期刊介绍: GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.
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