Nucleic Acids Res, 2009 Nov 13 38(Database issue). JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles.Įlodie Portales-Casamar, Supat Thongjuea, +7 authors, Andrew T Kwon, David Arenillas, Xiaobei Zhao, Eivind Valen, Dimas Yusuf, Boris Lenhard, Wyeth W Wasserman, Albin Sandelin. Robert E Thurman, Eric Rynes, +59 authors, Richard Humbert, Jeff Vierstra, Matthew T Maurano, Eric Haugen, Nathan C Sheffield, Andrew B Stergachis, Hao Wang, Benjamin Vernot, Kavita Garg, Sam John, Richard Sandstrom, Daniel Bates, Lisa Boatman, Theresa K Canfield, Morgan Diegel, Douglas Dunn, Abigail K Ebersol, Tristan Frum, Erika Giste, Audra K Johnson, Ericka M Johnson, Tanya Kutyavin, Bryan Lajoie, Bum-Kyu Lee, Kristen Lee, Darin London, Dimitra Lotakis, Shane Neph, Fidencio Neri, Eric D Nguyen, Hongzhu Qu, Alex P Reynolds, Vaughn Roach, Alexias Safi, Minerva E Sanchez, Amartya Sanyal, Anthony Shafer, Jeremy M Simon, Lingyun Song, Shinny Vong, Molly Weaver, Yongqi Yan, Zhancheng Zhang, Zhuzhu Zhang, Boris Lenhard, Muneesh Tewari, Michael O Dorschner, R Scott Hansen, Patrick A Navas, George Stamatoyannopoulos, Vishwanath R Iyer, Jason D Lieb, Shamil R Sunyaev, Joshua M Akey, Peter J Sabo, Rajinder Kaul, Terrence S Furey, Job Dekker, Gregory E Crawford, John A Stamatoyannopoulos. The accessible chromatin landscape of the human genome. Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young. Michael E Symonds, Sylvain P Sebert, Melanie A Hyatt, Helen Budge. Nutritional programming of the metabolic syndrome. M Ashburner, C A Ball, +17 authors, J A Blake, D Botstein, H Butler, J M Cherry, A P Davis, K Dolinski, S S Dwight, J T Eppig, M A Harris, D P Hill, L Issel-Tarver, A Kasarskis, S Lewis, J C Matese, J E Richardson, M Ringwald, G M Rubin, G Sherlock. Gene ontology: tool for the unification of biology. Mark M Pomerantz, Nasim Ahmadiyeh, +23 authors, Li Jia, Paula Herman, Michael P Verzi, Harshavardhan Doddapaneni, Christine A Beckwith, Jennifer A Chan, Adam Hills, Matt Davis, Keluo Yao, Sarah M Kehoe, Heinz-Josef Lenz, Christopher A Haiman, Chunli Yan, Brian E Henderson, Baruch Frenkel, Jordi Barretina, Adam Bass, Josep Tabernero, José Baselga, Meredith M Regan, J Robert Manak, Ramesh Shivdasani, Gerhard A Coetzee, Matthew L Freedman. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Our results suggest pervasive involvement of regulatory DNA variation in common human disease and provide pathogenic insights into diverse disorders.
We also demonstrated tissue-selective enrichment of more weakly disease-associated variants within DHSs and the de novo identification of pathogenic cell types for Crohn's disease, multiple sclerosis, and an electrocardiogram trait, without prior knowledge of physiological mechanisms. Disease-associated variants systematically perturb transcription factor recognition sequences, frequently alter allelic chromatin states, and form regulatory networks. We identified distant gene targets for hundreds of variant-containing DHSs that may explain phenotype associations. Eighty-eight percent of such DHSs are active during fetal development and are enriched in variants associated with gestational exposure-related phenotypes. We show that these variants are concentrated in regulatory DNA marked by deoxyribonuclease I (DNase I) hypersensitive sites (DHSs). Genome-wide association studies have identified many noncoding variants associated with common diseases and traits.
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