Eukaryotic gene expression is often tightly regulated by interactions between transcription factors (TFs) and their DNA cis targets. Yeast one-hybrid (Y1H) is one of the most extensively used methods to discover these interactions. We developed a high-throughput meiosis-directed yeast one-hybrid system using the Magic Markers of the synthetic genetic array analysis. The system has a transcription factor-DNA interaction discovery rate twice as high as the conventional diploid-mating approach and a processing time nearly one-tenth of the haploid-transformation method. The system also offers the highest accuracy in identifying TF-DNA interactions that can be authenticated in vivo by chromatin immunoprecipitation. With these unique features, this meiosis-directed Y1H system is particularly suited for constructing novel and comprehensive genome-scale gene regulatory networks for various organisms.

The aim of the present study was to determine the mutant genes and mutation sites in a family with maturity-onset diabetes of the young (MODY), in order to provide evidence for the diagnosis and treatment of clinical MODY. Based on the clinical characteristics of MODY, one family was selected from the Department of Endocrinology of Shanxi Provincial People's Hospital (Shanxi, China). The family comprised seven individuals, four of which were healthy (without MODY), and the whole exome of the individual with MODY, her father and her mother were sequenced. A suspected case (patient's uncle) and a healthy individual (patient's aunt) were sequenced for verification. The Q30 ratio was >90% in the family of three and the sequencing quality was good. The alignment rate was >95%, while the repeat sequence was <10%, with a mean sequencing depth of >120×, which is sufficient to identify mutations. According to Mutation Taster and LRT, it was predicted that the p.leu73Pro mutation of the pancreatic and duodenal homeobox 1 (PDX1) gene was deleterious. The mutation was verified by next-generation sequencing as the pathogenic site in this family. In conclusion, a novel mutation site of MODY type 4 in the PDX1 gene was identified in a family with MODY, which may provide a basis for its clinical treatment. Whole-exome sequencing appears to be of assistance in accurately diagnosing MODY.