Characterization of Celiac Disease-Related Epitopes and Gluten Fractions, and Identification of Associated Loci in Durum Wheat

Abstract

While durum wheat is a major food source in Mediterranean countries, storage (i.e., gluten) proteins are however responsible for celiac disease (CD), a serious autoimmune disease that occurs in genetically predisposed subjects. Different gluten epitopes—defined as “immunogenic” (IP) and “toxic” (TP) peptides—are involved in the pathology and their content in wheat grain depends on environmental and genetic factors. Detection of IP and TP is not trivial, and no work has been conducted so far to identify the genomic regions associated with their accumulation in wheat. In the present study, a genome-wide association study was performed on a durum wheat collection to identify marker–trait associations (MTAs) between 5730 high quality SNPs and the accumulation of CD-related peptides and gluten protein composition measured in two consecutive cropping seasons (2015/2016 and 2016/2017). High-molecular-weight glutenin subunits (HMW-GS) were more stable between the two years, and differences in total gluten proteins were mainly due to low-molecular-weight glutenin subunits (LMW-GS) and accumulation of gliadins. In the first instance, association tests were conducted on yellow pigment content (YP), a highly inheritable trait with a well-known genetic basis, and several significant MTAs were found corresponding to loci already known for being related to YP. These findings showed that MTAs found for the rest of the measured traits were reliable. In total, 28 significant MTAs were found for gluten composition, while 14 were found to be associated with IP and TP. Noteworthy, neither significant (−log10p > 4.7) nor suggestive (−log10p > 3.3) MTAs for the accumulation of CD-triggering epitopes were found on Gli-A1/Glu-A3 and Gli-B1/Glu-B3 loci, thus suggesting regulatory rather than structural gene effect. A PBF transcription factor on chromosome 5B, known to be involved in the regulation of the expression of CD-related peptides, was identified among the positional candidate genes in the LD-decay range around significant SNPs. Results obtained in the present study provide useful insights and resources for the long-term objective of selecting low-toxic durum wheat varieties while maintaining satisfactory gluten quality.

Novel Genetic Loci from Triticum timopheevii Associated with Gluten Content Revealed by GWAS in Wheat Breeding Lines

“…A stable locus was identified on chromosome 7B, which includes several closely linked markers. GC-associated markers for chromosome 7B were previously described in the literature [64], but their localization does not coincide with the locus mapped in our study. In the region of this locus, 21 genes were annotated, of which only TraesCS7B03G0016400 (RefSeq v. 1.1 TraesCS7B02G006800) is expressed in grain.…”

Unlocking the molecular basis of wheat straw composition and morphological traits through multi-locus GWAS

“…Therefore, despite several studies aiming to map the loci responsible for the solid stem phenotype, the underlying molecular mechanisms contributing to this key trait remain elusive. The validated SNP marker (RFL_Contig3228_2154) associated to SCSb in the present work was previously related to different trait such as grain weight and gluten component (HMW-GS, and LMW-GS) [13,61]. Now, this marker can be used for MAS to track differences in SCSb in tetraploid wheat accessions.…”

“…turgidum, turanicum and polonicum, while the modern cultivars were spread separately from the other samples. This large genetic variability of elite cultivars may be explained by the fact that they derived from national and international breeding programs developed during the last thirty years [13].…”

“…To overcome this issue, the exploration and exploitation of the genetic variability within wheat species appeared much more suitable to map the genetic determinants of the traits of interest. Genome-wide association study (GWAS) has been a routine and powerful approach for high-resolution genetic mapping of complex traits in plants [13]. Economically important traits include agronomic and yield associated traits (reviewed by [14] as well as biotic [15][16][17] and abiotic stress tolerance [18][19][20][21] have been mapped using GWAS in wheat.…”

The Diverse Potential of Gluten from Different Durum Wheat Varieties in Triggering Celiac Disease: A Multilevel In Vitro, Ex Vivo and In Vivo Approach

“…Full characterization of the 82 varieties can be found in Taranto et al (2020) [ 28 ]. Such a high variability might be attributed to high genetic variability among the studied varieties (i.e., matrix properties including protein structure and starch−protein interactions), which greatly influence digestive enzyme accessibility to gluten [ 29 , 30 ].…”