Dissecting the genetic causes of inflammatory bowel disease based on whole exome sequencing

IBD refers to the chronic inflammatory diseases of the gastrointestinal tract and mainly encompasses Crohn's disease (CD) and ulcerative colitis (UC). While genetic susceptibility is a major factor in the pathogenesis of IBD, the identification of causal gene variants remains challenging because the disease is heterogeneous. Whole-exome sequencing is an effective approach for identifying rare and novel variants in coding regions, providing critical insights into the genetic architecture of complex diseases like IBD. This study aimed to identify new genetic variants associated with IBD using WES in one family with familial IBD. We analyzed five individuals, three were affected and two persons were healthy, using high-throughput WES technology. Data processing involved quality control and trimming, alignment to the reference genome (GRCh۳۷) using hisat۲, and for variant calling using GATK toolkit. We identified a novel frameshift variant in FCGBP Gene (NM_۰۰۳۸۹۰.۲:chr۱۹-۴۰۳۹۹۴۵۹ TG>T, p.His۲۰۷۹Ilefs*۲۰). Gene implicated may be involved in the maintenance of the mucosal structure as a gel-like component of the mucosa. This variant exhibited in one patient in a family of under study that showed a strong connection with IBD and was absent in healthy controls. These findings demonstrate the use of WES in identifying the genetic causes of IBD and emphasize the role of GeneFCGBP in the development of IBD. This discovery opens up new possibilities for the identification of the mechanisms of disease, the development of new therapies, and the advancement of precision medicine in the treatment of IBD patients.

کلیدواژه ها:

inflammatory bowel disease (IBD) ، whole-exome sequencing (WES) ، gene variant ، novel mutation