Dr. Juan C. Martinez Cruzado

University of Puerto Rico, Mayaguez Campus

juancarlos.martinez@upr.edu

“Admixture Mapping of Diabetic Nephropathy Genetic Variants”

Project Summary

This is a pilot project submitted to the PR<INBRE Developmental Research Project Program aimed at identifying loci associated to diabetic nephropathy (DN) in Puerto Rico. It takes advantage of the uniquely extensive admixture in the Puerto Rico population to apply mapping by admixture linkage disequilibrium (MALD), a strategy more powerful than Genome<Wide Association Studies (GWAS) to identify disease< associated loci when applied to a population admixed for less than a few dozen generations. Subjects divided into two cohorts of 300 each will be genotyped for 300,000 SNPs, including several thousand ancestry<informative markers (AIMs). The cohorts will represent extreme phenotypes. The case cohort will be composed of relatively young patients, not more than 55 years of age, with medical diagnosis of nephropathy or showing high creatinine levels, including those undergoing dialysis treatment. The control cohort will be composed of patients diagnosed with diabetes for at least 15 years without having developed nephropathy or proteinuria, and presenting normal creatinine levels. Locus<genome comparisons for ancestry within cases and within controls will be performed, as well as case<control comparisons per locus, in search for excess ancestry. Loci showing statistically significant excess ancestry will likely possess ancestry<specific variants related to DN susceptibility or resistance. Thus, the proposed project will find the principal genetic loci (odds ratio > 1.5) leading to DN in Puerto Rico and will make a substantial contribution to the development of preventive and treatment strategies. The project responds to the PR<INBRE aim for promoting the continued development of biomedical research infrastructure in Puerto Rico. It counts with the collaboration of Dr. Cheryl A. Winkler, a leading admixture mapping expert at the National Cancer Institute, who will accept a student to learn and bring to Puerto Rico the know<how for admixture mapping analysis. It will also improve available admixture panels toward a better fit for the Puerto Rico population. In that way, this project will seed many admixture mapping studies in this uniquely admixed population with a very high potential to discover numerous disease<associated variants.