The Laboratory for Genetics and Genomic Medicine has had as a central theme, the development and application of novel approaches to identify causal genes for chronic inflammatory diseases such as Crohns’ Disease (CD), ulcerative colitis (UC) systemic lupus erythematosus (SLE) and multiple sclerosis (MS), as well as to determine their biological impact on health and disease. As a consequence, we have focused our efforts in the following areas:
This research began with our participation in the first large-scale identification, mapping, and genotyping of SNPs in the human genome. This was followed with the co-discovery of the fine haplotype structure of the human genome with our colleagues Daly, Hudson and Lander. We have been particularly interested in the major histocompatibility complex (MHC) region given its importance in transplantation, resistance to infection and susceptibility to immune mediated diseases.
We have successfully used targeted and genome-wide association studies (GWAS) to identify and validate hundreds of genetic risk factors either protect or predispose to common inflammatory diseases. In addition, we have used high-density genotyping and next generation sequencing (NGS) approaches for identifying the causal genes and variants within associated loci.
. The ultimate goal of our work is to translate genetic discoveries into a better understanding of complex biological systems, better clinical & research tools and improved therapies. To achieve this goal, it is important to develop methods and approaches to systematically generate functional data on putative causal genes & their variants, in models that provide the appropriate cellular context.
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Rivas MA et al. A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis. Nat Commun. 2016 Sep 13;7:12869. doi: 10.1038/ncomms12869 PMID: 27619887
Sivanesan D et al. IL23R (Interleukin 23 Receptor) Variants Protective against Inflammatory Bowel Diseases (IBD) Display Loss of Function due to Impaired Protein Stability and Intracellular Trafficking. J Biol Chem. 2016 Apr 15;291(16):8673-85. doi: 10.1074/jbc.M116.715870. Epub 2016 Feb 17. PMID: 26887945
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Beaudoin et al. Deep resequencing of GWAS loci identifies rare variants in CARD9, IL23R and RNF186 that are associated with Ulcerative colitis. PLoS Genet. 2013;9(9):e1003723. PMID:24068945
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