Evolutionary and structural analysis of genes associated with Type 2 Diabetes Mellitus

• Grant number: 18/11907-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2019
• End date: December 31, 2022
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: João Carlos Setubal
• Grantee: Diogo Maciel Duarte da Mota
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Diabetes Mellitus Type 02 (DM2) is a metabolic disease characterized by hyperglycemia derived from defects in the action of insulin and accounts for between 90-95% of cases of the disease. Its manifestation is dependent on mutant alleles at multiple gene loci; at the present time, there are at least 128 distinct signs of association with DM2 attributed to 113 loci. Due to the high prevalence of DM2, it is argued that most of these mutations must have had a neutral or positive character during the evolution of the human species. At present, the effect of these mutations on the splicing process and the regulation of the transcription process of the associated genes and their impact on human physiology is little known. Therefore, in the present project, we propose an analysis based on an evolutionary and structural study of the genes associated with T2DM with the objective of: 1) obtaining evidence about the possible tendency of these mutations to be located next to exonable exons; 2) to verify if genes containing mutations have a lower conservation of their gene expression profile throughout vertebrate evolution than the mean of similar expression profile genes that are not associated with DM; 3) to verify if the positions where the mutations associated to the DM are found do not present recurrent mutations throughout the evolution of vertebrates. The analysis of these data will allow to verify if the high prevalence of mutations associated with DM2 could be derived from the fact that they affect structures or patterns of expression that would be naturally more flexible and that, therefore, would have low deleterious potential. In addition, we will test whether the high prevalence could also be derived from a tendency of these sites to undergo recurrent mutations. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

MOTA, Diogo Maciel Duarte da. Analysis of genetic component of type 2 Diabetes Mellitus. 2024. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Física de São Carlos (IFSC/BT) São Carlos.