Triticeae Genomics and Genetics, 2024, Vol.15, No.2, 77-87 http://cropscipublisher.com/index.php/lgg 81 Figure 2 from Corsi et al. (2020) shows a Circos plot of the synthetic "W9784" ultralong sequence within the Chinese Spring wheat region (2B: 14,040,000-30,500,000 bp). The figure presents key genomic and gene features of this region through multilayer circular plots, including 705 assembled scaffolds with a total length of 3.47 Mb, spanning the broader Tsc2 locus. The plot details sequence homology, transposon element density, gene density, and the locations of candidate genes, marked with multiple SNP markers. The circular structure of the plot visually displays the distribution and association of these genes and markers on the chromosome, providing a clear visual tool for understanding the genetic structure of the ToxB sensitivity region. Furthermore, the gene Snn3-D1, identified in Aegilops tauschii, the D-genome progenitor of common wheat, has been implicated in susceptibility to Septoria nodorum blotch (SNB) through its interaction with the necrotrophic effector SnTox3 (Zhang et al., 2021). This gene's role in disease susceptibility highlights the complex genetic interactions that can influence wheat sensitivities. 4.2 Mechanisms of Non-Celiac wheat sensitivities Non-celiac wheat sensitivity (NCWS) is a condition characterized by gastrointestinal and extra-intestinal symptoms related to the ingestion of wheat, in the absence of celiac disease or wheat allergy. The pathophysiological mechanisms underlying NCWS are not well understood, and the diagnosis is primarily based on the exclusion of other wheat-related disorders and the presence of symptoms that improve on a gluten-free diet. Recent studies have begun to elucidate the genetic and molecular bases of NCWS. A genome-wide transcriptomic analysis of the intestinal mucosa from NCWS patients revealed significant differences in gene expression profiles compared to healthy controls. Specifically, 300 RNA transcripts were differentially expressed, with only 37% being protein-coding RNA and the remainder being non-coding RNA. This suggests a complex regulatory network involving non-coding RNA in the pathogenesis of NCWS. Principal component analysis and receiver operating characteristic curves indicated that these gene expression profiles could potentially distinguish NCWS patients from controls, highlighting the potential for developing diagnostic biomarkers (Efthymakis et al., 2020). Further analysis of these differentially expressed genes pointed to the involvement of the innate immune response, the hedgehog signaling pathway, and circadian rhythm dysregulation in NCWS. These findings suggest that NCWS may result from a deranged immune response, possibly triggered by gluten or other wheat components. The role of non-coding RNA in regulating these pathways underscores the importance of regulatory genetic circuits in the disease mechanism (Efthymakis et al., 2020). 4.3 Genetic factors influencing wheat sensitivities Wheat sensitivities, including celiac disease (CD) and non-celiac wheat sensitivity (NCWS), are influenced by various genetic factors. The immunological reactivity to gluten proteins, particularly gliadins and glutenins, plays a crucial role in these conditions. Research has shown that domestication and breeding of wheat have led to a decrease in the content of gliadins, which are known to contain immunogenic epitopes associated with CD (Ozuna and Barro, 2018). Specifically, the genomes of certain wheat species, such as those with DD, BBAADD, and RR types, have been found to have a higher frequency of CD immunogenic epitopes (Ozuna and Barro, 2018). Moreover, the identification of genetic mutations that lower gluten content in wheat has been a significant advancement. For instance, the inactivation of a transcription factor in barley, which was then applied to wheat, resulted in a substantial reduction in gliadin and low-molecular-weight glutenin accumulation by 50% to 60% (Moehs et al., 2019). This genetic modification also increased the levels of lysine, an essential amino acid, by 33%, potentially offering a wheat alternative for individuals with gluten sensitivities (Moehs et al., 2019). 4.4 Diagnostic methods for wheat sensitivities The diagnosis of wheat sensitivities involves both molecular and immunological approaches. One of the key diagnostic methods is the identification of specific wheat allergens that trigger immune responses in sensitive individuals. For example, Tri a 36, a low molecular weight glutenin, has been characterized as a major wheat food allergen. This allergen reacts with IgE antibodies in approximately 80% of wheat food-allergic patients and shows
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