There has been an explosion of new genetic, biochemical, and cell biologic techniques. Appropriate systems biology tools are needed to facilitate integration of genotyping information, mRNA expression, microRNA expression, promoter analysis, proteome expression, and metabolome profiles in order to identify key biological processes and their interactions. In addition to better computational tools, a deeper understanding ...more »
Metabolic control alone does not predict an individual’s risk for diabetic complications. Family studies suggest that genetic factors play an important role in the predisposition for a specific type of complication and its progression. In addition to more classic genetics, research in this area has expanded to epigenetics and non-coding RNA. Epigenetic marks include modifications to the DNA or chromatin that do not ...more »
Identifying robust association between genetic variation and severe human CKD phenotypes has been hindered by lack of collections of patient sample collection of sufficient size to use effectively in GWAS. The community could address this issue by developing reproducible but simple clinical phenotyping criteria and collecting samples from ESRD patients in dialysis units. Contrast can be made to publicly available datasets ...more »
It has been difficult to identify SNPs with even modest effects in studies of type 2 diabetic nephropathy. One possible explanation is that patients with kidney disease who have type 2 diabetes may not have a single disease. Indeed the old biopsy data suggest that there is a diversity of diseases in this population. Should gene finding efforts focus exclusively on type 1 diabetic nephropathy for the short term?
One explanation for the discordant response of agents that treat complications in rodents versus humans is that deleterious pathways that are responsive to a certain drug may be widely expressed in inbred animal models, but expressed in only a small number of individuals. Should some agents be tested in primates or some other larger mammal? Pharmacogenomic, pharmacometabolomic, and pharmacoproteomic approaches could ...more »
While the mouse has many advantages, the human diabetic nephropathy phenotype has been difficult to faithfully replicate in the mouse using candidate gene approaches. Future work should focus on developing "humanized mice," in which loci associated with human diabetic complications are knock-in to the mouse. These animals could then be used to study mechanisms and therapeutics using systems biology approaches.
Non-mammalian model organisms have been underutilized to understand diabetic nephropathy pathogenesis. These simple model organism systems that permit ease of genetic manipulation, rapid throughput and precise measurement of phenotypes. Work published earlier this year (PNAS 107: 775, 2010) demonstrated that type 2 DM risk loci could be characterized in zebrafish. Interestingly, this study demonstrated this study shows ...more »