Katholieke Universiteit Leuven

About: Katholieke Universiteit Leuven is a education organization based out in Leuven, Belgium. It is known for research contribution in the topics: Population & Transplantation. The organization has 61109 authors who have published 176584 publications receiving 6210872 citations.

Transient Receptor Potential Cation Channels in Disease

Abstract: The transient receptor potential (TRP) superfamily consists of a large number of cation channels that are mostly permeable to both monovalent and divalent cations. The 28 mammalian TRP channels can be subdivided into six main subfamilies: the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and the TRPA (ankyrin) groups. TRP channels are expressed in almost every tissue and cell type and play an important role in the regulation of various cell functions. Currently, significant scientific effort is being devoted to understanding the physiology of TRP channels and their relationship to human diseases. At this point, only a few channelopathies in which defects in TRP genes are the direct cause of cellular dysfunction have been identified. In addition, mapping of TRP genes to susceptible chromosome regions (e.g., translocations, breakpoint intervals, increased frequency of polymorphisms) has been considered suggestive of the involvement of these channels in hereditary diseases. Moreover, strong indications of the involvement of TRP channels in several diseases come from correlations between levels of channel expression and disease symptoms. Finally, TRP channels are involved in some systemic diseases due to their role as targets for irritants, inflammation products, and xenobiotic toxins. The analysis of transgenic models allows further extrapolations of TRP channel deficiency to human physiology and disease. In this review, we provide an overview of the impact of TRP channels on the pathogenesis of several diseases and identify several TRPs for which a causal pathogenic role might be anticipated.

Assessing computational tools for the discovery of transcription factor binding sites.

Abstract: The prediction of regulatory elements is a problem where computational methods offer great hope. Over the past few years, numerous tools have become available for this task. The purpose of the current assessment is twofold: to provide some guidance to users regarding the accuracy of currently available tools in various settings, and to provide a benchmark of data sets for assessing future tools.

A polygenic burden of rare disruptive mutations in schizophrenia

Abstract: Schizophrenia is a common disease with a complex aetiology, probably involving multiple and heterogeneous genetic factors. Here, by analysing the exome sequences of 2,536 schizophrenia cases and 2,543 controls, we demonstrate a polygenic burden primarily arising from rare (less than 1 in 10,000), disruptive mutations distributed across many genes. Particularly enriched gene sets include the voltage-gated calcium ion channel and the signalling complex formed by the activity-regulated cytoskeleton-associated scaffold protein (ARC) of the postsynaptic density, sets previously implicated by genome-wide association and copy-number variation studies. Similar to reports in autism, targets of the fragile X mental retardation protein (FMRP, product of FMR1) are enriched for case mutations. No individual gene-based test achieves significance after correction for multiple testing and we do not detect any alleles of moderately low frequency (approximately 0.5 to 1 per cent) and moderately large effect. Taken together, these data suggest that population-based exome sequencing can discover risk alleles and complements established gene-mapping paradigms in neuropsychiatric disease.

Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer

Abstract: Background Patients with a germline BRCA1 or BRCA2 mutation make up a small subgroup of those with metastatic pancreatic cancer. The poly(adenosine diphosphate–ribose) polymerase (PARP) in...