Using Whole Exome Sequencing (WES) to identify genes underlying unexplained Maturity Onset Diabetes of the Young (MODY-X)

一些罕见的糖尿病是纯粹遗传的，不受环境的影响，也就是说，它们只是由于通过家庭传递的基因的DNA序列的破坏性变化。这种罕见形式的一种类型被称为年轻人的成熟型糖尿病（MODY），因为它类似于常见的2型糖尿病（T2D），通常见于40岁以上的人，但发生在年轻时，低于20岁。到目前为止，已经有七个基因被证明会引起MODY，但许多MODY病例的原因仍然未知。随着DNA测序技术的新进展，有可能检查一个人的所有DNA吗？人类的基因组被翻译成构成健康人的物质。利用这项技术，该提案旨在确定六个不相关家庭中导致MODY的DNA序列变化。这可能会改善更多MODY家族的诊断，并可能影响他们的治疗，因为以前的研究结果使MODY患者能够成功地用磺脲类药物治疗，而不是每天注射胰岛素。以前对MODY的研究也有助于对常见T2D遗传学的理解做出重大贡献，并且有充分的理由相信目前的提案也将对T2D领域做出重大贡献。

Some rare forms of diabetes are purely inherited and are unaffected by the environment, that is they are only due to damaging changes in the DNA sequence of a gene that is passed down through a family. One type of this rare form is called maturity-onset diabetes of the young (MODY), because it resembles common type 2 diabetes (T2D), which is usually seen in people over 40 years, but occurs at a young age, below about 20 years. Seven genes so far have been shown to give rise to MODY but many MODY cases are still of unknown cause. With new advances in DNA sequencing technologies, it is possible to examine all of the DNA in a person?s genome that is translated into the products that go to make up a healthy person. Using this technology, this proposal will aim to identify the changes in the DNA sequence that are responsible for MODY in six unrelated families. This is likely to improve the diagnosis of further MODY families and may affect their treatment as previous findings have enabled MODY patients to be successfully treated with sulfonylureas rather than daily insulin injection. Previous research into MODY has also helped make a significant contribution to the understanding of the genetics of common T2D and there is every reason to believe that the current proposal will also contribute something significant to the T2D field.