Search for novel MODY genes with exome sequencing

青年成熟型糖尿病(MODY)是一种以常染色体显性遗传为特征的糖尿病，发病年龄在25岁之前。虽然已经报道了13个MODY基因，但在日本MODY家族中还没有发现一个主要的易感基因。本研究用Sanger测序法测定了8个日本MODY家系的易感基因(葡萄糖激酶p.T228M、p.G246R、p.C371Y和p.G446D，HNF-1A的p.E274K，HNF-1B的p.R276H和p.S461I，ABCC8的p.P1198L)。此外，我们还进行了全外显子组测序，即对人类基因组蛋白质编码区域进行定向测序，以确定一个新的MODY易感基因。我们获得了整个靶向外显子的50X中位数覆盖率，并在一个MODY家族中发现了几个罕见的非同义变异与糖尿病共分离。

Maturity-onset diabetes of the young (MODY) is a diabetes characterized by an autosomal-dominant mode of inheritance and an onset before the age of 25 years. Although thirteen MODY genes have been reported, a major susceptibility gene in Japanese MODY families has not been identified. In this study, we determined susceptibility genes in 8 Japanese MODY families (p.T228M, p.G246R, p.C371Y and p.G446D in glucokinase, p.E274K in HNF-1A, p.R276H and p.S461I in HNF-1B, p.P1198L in ABCC8) with Sanger sequencing. Furthermore, we carried out whole-exome sequencing which is the targeted sequencing of the human genome region that is protein coding to identify a new susceptibility gene for MODY. We obtained 50 X median coverage of the entire targeted exome and found several rare non-synonymous variants co-segregated with diabetes in a MODY family.