Integrating a genome-wide association study with a large-scale transcriptome analysis to predict genetic regions influencing the glycaemic index and texture in rice.

Roslen Anacleto,Nese Sreenivasulu,Trinidad P Trinidad,Gopal Misra,Rosa Paula Cuevas,Sabiha Parween,Vito M Butardo,Aida C Mallillin,Saurabh Badoni,Cecilia Acuin,Matthew K Morell,Markus Kuhlmann,Anthony R Bird

doi:10.1111/pbi.13051

Abstract

SummaryReliably 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.

Highlights

The global rise in obesity has affected 2.1 billion adults and 422 million of these adults have Type II diabetics; obesity is the leading cause of non-communicable disease (NCD) (Brand-Miller, 2003; Scully, 2012; Shetty, 2012; World Health Organization, 2016)
This finding was evidenced in three cultivars, which despite bearing the lowest glycaemic index (GI) values plotted at opposite ends of the final viscosity (FV) range (Figure 1b)
This fine-mapped hotspot region in chromosome 6 harbour key genes such as GBSSI that potentially play specific roles in the mediating high GI to intermediate GI through alternative spliced single nucleotide polymorphisms (SNPs) sitting in exon 1 and another in exon 10 influencing lower FV

Summary

Introduction

The global rise in obesity has affected 2.1 billion adults and 422 million of these adults have Type II diabetics; obesity is the leading cause of non-communicable disease (NCD) (Brand-Miller, 2003; Scully, 2012; Shetty, 2012; World Health Organization, 2016). Various factors, such as urbanization, the shift to an energy-rich Western diet, a sedentary lifestyle and genetic predisposition, impact the development of diabetes mellitus. A low-GI diet including slower digestible rice improves metabolic health and is helpful in improving insulin sensitivity, which can mitigate the prevalence of associated diseases (Brand-Miller, 2003)

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