Whole exome sequencing reveals rare variants linked to congenital pouch colon

Abstract

We demonstrate the application of whole exome sequencing to discover the rare variants for congenital pouch colon, acronymed CPC. For 18 affected individuals in a total of 64 samples, we sequenced coding regions to a mean coverage of 100×. A sufficient depth of ca. 94% of targeted exomes was achieved. Filtering against the public SNP/variant repositories, we identified a host of candidate genes, EPB41L4A and CTC1 associated with colon, neural/brain muscles and Dyskeratosis Congenita maladies. Furthermore, the stop gain mutations in the form of JAG1,OR5AR1,SLC22A24,PEX16,TSPAN32,TAF1B,MAP2K3 and SLC25A19 appears to be localized to Chromosomes 2, 11, 17 and 20 in addition to the three stop lost mutations across three genes, viz. OAS2, GBA3 and PKD1L2 affecting the colon tissue. While our results have paved way for transcendence of monogenic traits in identifying the genes underlying rare genetic disorders, it will provide helpful clues for further investigating genetic factors associated with anorectal anomalies, particularly CPC.

Lnc-EPB41-Protein Interactions Associated with Congenital Pouch Colon

“…Since 2005, several efforts have been made to understand the clinical genetic makeup of CPC, but no attempt has been made to study the genes responsible for the disease. Recently, we have screened 64 subjects out of which 18 affected samples were analysed using whole exome sequencing (WES) [ 3 ]. Identifying mutations and variants in both coding and non-coding regions affecting such phenotypes are not only of valuable interest towards clinical applications but are also important for enormous prognostic value for therapy.…”

“…As the lncRNAs play a role in regulation [ 18 ], there is an enormous scope for ascertaining lncRNA-protein interactions. In this study, we inferred a lncRNA, viz.lnc-EPB41-1-1promiscuously interacting with six protein-coding genes and established its interaction with KIF13A, a 202 kDa trafficking protein [ 19 ] and a bona fide gene causal to CPC [ 3 ]. Furthermore, this kinesin family of microtubule-based motor proteins is known to regulate various processes such as mannose-6-phosphate receptor (M6PR) transport besides mediating melanosome biogenesis and cytokinesis.…”

Clinical prognostic implications of EPB41L4A expression in multiple myeloma

“…312) It was found by WES that EPB41L4A has genetic susceptibility to colon, nerve/brain muscle and congenital keratosis. (20) To understand the role of EPB41L4A in cancer, studies have explored the role of EPB41L4A in cell lines. This study found that when β-catenin was depleted in SW480 cells, the RNA expression of EPB41L4A was significantly reduced (SW480 cells are colorectal cancer cell lines).…”

“…(19) Only a few studies have shown that EPB41L4A has genetic susceptibility to colon, nerve/brain muscle and congenital keratosis. (20) However, there is currently no clinical prognostic study on the EPB41L4A gene in any types of cancer. The study integrates multiple data from MM to achieve three goals.…”

Whole exome-trio analysis reveals rare variants associated with Congenital Pouch Colon

“…respectively (Mathur et al, 2018). In a separate study, we have also inferred the role of long non-coding RNAs (lncRNAs) from a WES and identified lnc-EPB41-1-1, located in the intergenic regions of EPB41 that is known to be interacting with KIF13A (Gupta et al, 2018).…”