Xitiz Chamling and Johnny Cruz Corchado will present their research on 17th November, 2011
Background for Xitiz Chamlings talk:
A novel BBSome interacting protein is an ADP/ATP translocase, SLC25A31
Chamling X.1, Seo S.3, Sheffield V.C.1,2,3
1Department of Pediatrics, Interdisciplinary program of genetics University of Iowa, Iowa City IA 52242 2Department of Pediatrics, Howard Hughes Medical Institute, IA 52242 and 3Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa, IA 52242
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder characterized by obesity, retinal degeneration, polydactyly, hypogenitalism and renal defects. At least 15 different BBS genes have been reported. Recent findings have implicated BBS with primary cilia dysfunction, and BBS proteins are thought to be involved in the trafficking of various ciliary proteins. Specifically, the BBSome, a stable complex of seven highly conserved BBS proteins, BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9 and a novel protein, BBBIP10, is believed to traffic to cilia bringing various cargos along with it. In recent studies, various different interacter proteins including the leptin receptor, Rabin 8, PCM1 and few others have been associated with the BBSome. Due to the pleiotropic nature of the disease and the abundance of proteins in and around cilia where BBS proteins localize, we hypothesized that there are other proteins that interact with the BBSome which have not been identified. To investigate this hypothesis we generated a transgenic (LAP-BBS4) mouse line that expresses LAP tagged BBS4 in multiple different tissues including eye, brain and testis. Using lysates from brain and testis of the transgenic mouse, we pulled down BBSome interacters. Mass spectrometry confirmed one specific interacting protein to be SLC25A31 (solute carrier family 25 member 31), also known as ADP/ATP translocase 4 or Ant4.
Background for Johnny Cruz Corchado’s talk:
Identification of new genetic variants in Dense Deposit Disease using sequence capture of complement and complement related genes
Johnny Cruz Corchado1,2, Bu Fengxiao2, Tara Maga1,2, Richard J. Smith1,2
1Department of Otolaryngology – Head and Neck Surgery, University of Iowa, Iowa City, IA, USA, 2 Interdepartmental PhD Program in Genetics, Department of Otolaryngology, University of Iowa, Iowa City, Iowa City, IA, USA
Dense Deposit Disease (DDD) is a complement mediated disease that leads to renal failure in 50% of affected patients. Its genetics are complex but underlying disease pathogenesis is uncontrolled fluid-phase activation of the alternative pathway (AP) of the complement system. Genetic variability in the complement AP is associated with DDD, but most of the patients do not present a pathological variant in the genes screened. Therefore, we sought to identify novel pathogenic variants by increasing the number of genes screened. In addition, we sought to define a more comprehensive DDD “at risk” haplotype by identifying new polymorphic variants that segregate preferentially with the disease. We completed a focused targeted-sequence capture of 85 complement and complement-related genes that may play a role in DDD. This in-house developed platform called CASCADE includes genes in the three pathways of the complement system, regulators of the complement activity (RCA), and other complement related genes. Herein we report our preliminary findings and experience with 15 DDD patients using CASCADE.