Katie Weihbrecht and Fengxiao Bu will present their research on May 16th 2013
Katie’s Research Abstract:
Nephronophthisis (NPHP) is a recessive kidney disorder that is the leading cause of early onset, end-stage renal failure. Localization to the ciliary-centrosomal complex of many proteins mutated in cystic kidney disease provided a coalescing mechanism for NPHP-related ciliopathies (NPHP-RC). Aside from renal failure and kidney cysts, the two other main phenotypes are retinal and cerebellar degeneration. One such disease with NPHP-RC phenotypes is Bardet-Biedl Syndrome (BBS), with cardinal phenotypes of retinal degeneration, renal abnormalities, obesity, polydactyl, and learning disabilities. An NPHP gene associated with BBS is serologically defined colon cancer antigen 8 (SDCCAG8) later defined as NPHP10. However, the association with this disease was only recently made and little is known about the molecular function and how it leads to the observed phenotypes. BBS patients with NPHP10 mutations exhibit retinal and renal abnormalities, obesity, and learning disabilities. The purpose of this study is to identify and characterize the interactions of NPHP10 and determine how these interactions lead the different phenotypes seen in patients. NPHP10 has not been shown to be involved in the pathway that the other NPHP genes are involved in nor has it been shown as an interactor with the other current BBS genes. Thus, the pathway through which NPHP10 leads to BBS phenotypes is novel and will provide further insight into potential BBS candidate genes. Along with a biochemical approach to the characterization of this gene, a knockout mouse model has recently become available. Current work involves characterizing the phenotypes of this mouse and how the biochemical data we currently have correlate with the phenotypes seen in an organism model.
Bu’s Research Abstract:
Targeted mass parallel sequencing for gene screening in atypical hemolytic uremic syndrome
Atypical hemolytic uremic syndrome (aHUS) is a rare renal disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. About 50% of aHUS cases progress to end-stage renal failure, with the death rate as high as 25%. Previous studies of aHUS have implicated genetic variation in multiple genes in complement pathway in disease pathogenesis, defining the causative mechanism as complement dysregulation at the cell surface level. This understanding improved the disease treatment, and significantly changed the prognosis of aHUS patients. However, it still remains major challenges in understanding the uncovered detailed picture of aHUS at the genetic level. Evidences suggest, beside of the complement pathway, the coagulation pathway may also paly important role in the disease. We are using an optimized platform called CasCADE (Capture and Sequencing of Complement-Associated Disease Exons), which is based on targeted sequence capture and mass parallel sequencing, to screen affected subjects for genetic variation in 85 candidate genes prioritized and selected from the complement pathway and coagulation pathway. Data analysis, including sequencing results qualification control, reads alignment, variant calling, annotation, and filtering, will be conducted on the University of Iowa Galaxy Bioinformatics Server using CLCG Illumina Paired-End Workflow. The on-going project would reveal more genetic abnormalities in aHUS subjects; improve understanding of disease mechanism; and response to therapy strategies.