RT Journal Article SR Electronic T1 Development of reduced gluten wheat enabled by determination of the genetic basis of the lys3a low hordein barley mutant JF bioRxiv FD Cold Spring Harbor Laboratory SP 354548 DO 10.1101/354548 A1 Charles P. Moehs A1 William J. Austill A1 Aaron Holm A1 Tao A. G. Large A1 Dayna Loeffler A1 Jessica Mullenberg A1 Patrick S. Schnable A1 Wayne Skinner A1 Jos van Boxtel A1 Liying Wu A1 Cate McGuire YR 2018 UL http://biorxiv.org/content/early/2018/06/23/354548.abstract AB Celiac disease is the most common food-induced enteropathy in humans with a prevalence of approximately 1% world-wide [1]. It is induced by digestion-resistant, proline- and glutamine-rich seed storage proteins, collectively referred to as “gluten,” found in wheat. Related prolamins are present in barley and rye. Both celiac disease and a related condition called non-celiac gluten sensitivity (NCGS) are increasing in incidence [2] [3]. This has prompted efforts to identify methods of lowering gluten in wheat, one of the most important cereal crops. Here we used BSR-seq (Bulked Segregant RNA-seq) and map-based cloning to identify the genetic lesion underlying a recessive, low prolamin mutation (lys3a) in diploid barley. We confirmed the mutant identity by complementing the lys3a mutant with a transgenic copy of the wild type barley gene and then used TILLING (Targeting Induced Local Lesions in Genomes) [4] to identify induced SNPs (Single Nucleotide Polymorphisms) in the three homoeologs of the corresponding wheat gene. Combining inactivating mutations in the three sub-genomes of hexaploid bread wheat in a single wheat line lowered gliadin and low molecular weight glutenin accumulation by 50-60% and increased free and protein-bound lysine by 33%. This is the first report of the combination of mutations in homoeologs of a single gene that reduces gluten in wheat.