Type 2 Diabetes Susceptibility Gene Structure Analysis And Serum Proteome Research

The study focused on the mechanism of type 2 diabetes in both structure of single gene and variation of serum protein profile. It was divided into two parts, 1) finding the nuclear localization signals in soluble adenylyl cyclase (sAC), and 2) evaluating the change of protein profile during the course of type 2 diabetes.Based on the previous research of our lab, the SNP in sAC gene showed significantly statistical difference. It suggested that sAC was related to type 2 diabetes in Chinese Han Population. Soluble adenylyl cyclase was a newly reported adenylyl cyclase, which had a unique subcellular localization differed from trans-membrane adenylyl cyclase. It located inside the nuclei, far away from cell membrane. And it might be responsible for cAMP-related signal transduction pathways in nuclei. Bioinformatics analysis showed no known nuclear localization signals inside the sequence of sAC. In this research, we focused on the truncated-sAC (tsAC), which could be detected in most tissues. Multiple mutants were constructed and expressed in eukaryotic cell. By observing subcellular localization of these mutants one by one, we located two domains in sAC related with its nuclear localization. These two domains connected with its catalytic domains, suggested that some function of sAC could be strict conserved and unreplaceable.Next, we used comparative proteomic method to evaluate the change of protein profile during the course of type 2 diabetes.Proteomics emerged with the recent achievement in genome research and quick promotion in biological technologies.Through the analysis of variant protein profiles, the gene research results are combined with the study outcomes of functions. In disease research, proteomic approach was adopted to compare the samples obtained from disease cases and matched control group. It helped to identify biomarkers of different diseases and contributed a lot to both early diagnosises and clinically treatments. In this part, serum sample of type 2 diabetes patients were analyzed. A group of 732 serum samples was...