Integrating a genome-wide association study with a large-scale transcriptome analysis to predict genetic regions influencing the glycaemic index and texture in rice
Integrating a genome-wide association study with a large-scale transcriptome analysis to predict genetic regions influencing the glycaemic index and texture in rice
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DOI：
10.1111/pbi.13051
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发表时间：
2019-07-01
影响因子：
13.8
通讯作者：
Sreenivasulu, Nese
中科院分区：
文献类型：
--
作者：
Anacleto, Roslen;Badoni, Saurabh;Sreenivasulu, Nese
鉴于亚洲II型糖尿病发病率高，稻米是主食，可靠地生产低血糖指数（GI）的稻米品种是一项重要的营养干预措施。我们整合了全基因组关联研究（GWAS）和全转录组关联研究（TWAS），以确定水稻GI的遗传基础。GWAS利用了305个重新测序的不同籼稻组，包括240万个在基因区域富集的单核苷酸多态性（SNP）。在LOC_Os05g03600外显子2的同义SNP处检测到一种新的关联信号，用于中至高GI表型变异。另一个主要的热点区域被预测为贡献中至高GI变异，涉及6号染色体上的26个基因（GI6.1）。这些基因包括GBSSI、两个水解酶基因、参与信号传导和染色质修饰的基因。TWAS和甲基化组测序数据揭示了在热点GI6.1区域中具有差异甲基化模式的顺式作用功能相关遗传变体，将靶标缩小到13个基因。相反，GBSSI的启动子区及其选择性剪接等位基因（Wx（a）的G等位基因）解释了中至高GI变异。在前面的分析中还强调了外显子-10处的SNP（C>T）以影响最终粘度（FV），其独立于直链淀粉含量/GI。GC单倍型的低GI系质地较软，而GT单倍型的两个低GI系质地较硬且有粘性。通过临床体内研究进一步证实了低GI线。基因调控网络分析强调了非淀粉多糖途径在降低GI中的作用。
Reliably generating rice varieties with low glycaemic index (GI) is an important nutritional intervention given the high rates of Type II diabetes incidences in Asia where rice is staple diet. We integrated a genome-wide association study (GWAS) with a transcriptome-wide association study (TWAS) to determine the genetic basis of the GI in rice. GWAS utilized 305 re-sequenced diverse indica panel comprising 2.4 million single nucleotide polymorphisms (SNPs) enriched in genic regions. A novel association signal was detected at a synonymous SNP in exon 2 of LOC_Os05g03600 for intermediate-to-high GI phenotypic variation. Another major hotspot region was predicted for contributing intermediate-to-high GI variation, involves 26 genes on chromosome 6 (GI6.1). These set of genes included GBSSI, two hydrolase genes, genes involved in signalling and chromatin modification. The TWAS and methylome sequencing data revealed cis-acting functionally relevant genetic variants with differential methylation patterns in the hot spot GI6.1 region, narrowing the target to 13 genes. Conversely, the promoter region of GBSSI and its alternative splicing allele (G allele of Wx(a)) explained the intermediate-to-high GI variation. A SNP (C>T) at exon-10 was also highlighted in the preceding analyses to influence final viscosity (FV), which is independent of amylose content/GI. The low GI line with GC haplotype confirmed soft texture, while other two low GI lines with GT haplotype were characterized as hard and cohesive. The low GI lines were further confirmed through clinical in vivo studies. Gene regulatory network analysis highlighted the role of the non-starch polysaccharide pathway in lowering GI.