Whole Exome Sequencing of Crohn's Disease Pedigrees
Final Report Abstract
The project was started by sequencing cases from multiplex families with inflammatory bowel disease with the goal of detecting novel variants causing IBD. Clustering of patients within a pedigree may point to variants with larger effects on disease compared to those identified in GWAS and even monogenic forms of IBD. However, our results rather point to an accumulation of a large number of common susceptibility alleles in the pedigree. Subsequently, we turned our focus to severe early-onset cases of IBD, since the most informative characteristics indicating the presence of a highly penetrant genetic cause are an early age of onset and a very severe course of disease. We were able to show a general enrichment of variants in primary immunodeficiency genes in early-onset IBD compared to adult-onset IBD cases and healthy controls. In addition, we detected likely monogenic causes of disease in the genes IL2RG, IL10, WAS, DKC1 and NOX1 in a number of cases, supporting the application of exome sequencing for these early-onset cases, also in the future.
Publications
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(2017) Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea. Inflammatory bowel diseases 23 (12) 2109–2120
Petersen, Britt-Sabina; August, Dietrich; Abt, Renate; Alddafari, Moudjahed; Atarod, Lida; Baris, Safa; Bhavsar, Hemant; Brinkert, Florian; Buchta, Mary; Bulashevska, Alla; Chee, Ronnie; Cordeiro, Ana I.; Dara, Naghi; Dückers, Gregor; Elmarsafy, Aisha; Fr
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(2018) Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population. PLoS genetics 14 (5) e1007329
Rivas, Manuel A.; Avila, Brandon E.; Koskela, Jukka; Huang, Hailiang; Stevens, Christine; Pirinen, Matti; Haritunians, Talin; Neale, Benjamin M.; Kurki, Mitja; Ganna, Andrea; Graham, Daniel; Glaser, Benjamin; Peter, Inga; Atzmon, Gil; Barzilai, Nir; Levin
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“Exome sequencing analysis reveals variants in primary immunodeficiency genes in patients with very early onset inflammatory bowel disease.” Gastroenterology, vol. 149, no. 6, pp. 1415–24, Nov. 2015
J. R. Kelsen, N. Dawany, C. J. Moran, B.-S. Petersen, M. Sarmady, A. Sasson, H. Pauly-Hubbard, A. Martinez, K. Maurer, J. Soong, E. Rappaport, A. Franke, A. Keller, H. S. Winter, P. Mamula, D. Piccoli, D. Artis, G. F. Sonnenberg, M. Daly, K. E. Sullivan, R. N. Baldassano, and M. Devoto
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“The genetics of Crohn’s disease and ulcerative colitis – status quo and beyond.” Scand. J. Gastroenterol., vol. 50, no. 1, pp. 13–23, Jan. 2015
D. Ellinghaus, J. Bethune, B.-S. Petersen, and A. Franke
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“Opportunities and challenges of whole-genome and -exome sequencing. BMC Genet., vol. 18, no. 1, pp. 1-14, Feb. 2017
B.-S. Petersen, B. Fredrich, M. P. Hoeppner, A. Franke
