Genetic analysis of four consanguineous multiplex families with inflammatory bowel disease
| Autor: | Saleh Daher, Matthew Frampton, Elena R. Schiff, Anthony W. Segal, Eran Israeli, Noam Ben-Yosef, Adam P. Levine, Fadi Abu Baker, Rifaat Safadi |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
business.industry Gastroenterology Original Articles medicine.disease Inflammatory bowel disease Genetic analysis digestive system diseases 03 medical and health sciences 0302 clinical medicine inflammatory bowel disease Immunology medicine family study genetics Multiplex homozygosity business 030217 neurology & neurosurgery AcademicSubjects/MED00260 030304 developmental biology |
| Zdroj: | Gastroenterology Report |
| ISSN: | 2052-0034 |
| DOI: | 10.1093/gastro/goab007 |
| Popis: | Background Family studies support a genetic predisposition to inflammatory bowel diseases (IBD), but known genetic variants only partially explain the disease heritability. Families with multiple affected individuals potentially harbour rare and high-impact causal variants. Long regions of homozygosity due to recent inbreeding may increase the risk of individuals bearing homozygous loss-of-function variants. This study aimed to identify rare and homozygous genetic variants contributing to IBD. Methods Four families with known consanguinity and multiple cases of IBD were recruited. In a family-specific analysis, we utilised homozygosity mapping complemented by whole-exome sequencing. Results We detected a single region of homozygosity shared by Crohn's disease cases from a family of Druze ancestry, spanning 2.6 Mb containing the NOD2 gene. Whole-exome sequencing did not identify any potentially damaging variants within the region, suggesting that non-coding variation may be involved. In addition, affected individuals in the families harboured several rare and potentially damaging homozygous variants in genes with a role in autophagy and innate immunity including LRRK1, WHAMM, DENND3, and C5. Conclusion This study examined the potential contribution of rare, high-impact homozygous variants in consanguineous families with IBD. While the analysis was not designed to achieve statistical significance, our findings highlight genes or loci that warrant further research. Non-coding variants affecting NOD2 may be of importance in Druze patients with Crohn's disease. |
| Databáze: | OpenAIRE |
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