Abstract
We investigated whether likely pathogenic variants co-segregating with gastroschisis through a family-based approach using bioinformatic analyses were implicated in body wall closure. Gene Ontology (GO)/Panther functional enrichment and protein-protein interaction analysis by String identified several biological networks of highly connected genes in UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, AOX1, NOTCH1, HIST1H2BB, RPS3, THBS1, ADCY9, and FGFR4. SVS–PhoRank identified a dominant model in OR10G4 (also as heterozygous de novo), ITIH3, PLEKHG4B, SLC9A3, ITGA2, AOX1, and ALPP, including a recessive model in UGT1A7, UGT1A6, PER2, PTPRD, and UGT1A3. A heterozygous compound model was observed in CDYL, KDM5A, RASGRP1, MYBPC2, PDE4DIP, F5, OBSCN, and UGT1A. These genes were implicated in pathogenetic pathways involving the following GO related categories: xenobiotic, regulation of metabolic process, regulation of cell adhesion, regulation of gene expression, inflammatory response, regulation of vascular development, keratinization, left-right symmetry, epigenetic, ubiquitination, and regulation of protein synthesis. Multiple background modifiers interacting with disease-relevant pathways may regulate gastroschisis susceptibility. Based in our findings and considering the plausibility of the biological pattern of mechanisms and gene network modeling, we suggest that the gastroschisis developmental process may be the consequence of several well-orchestrated biological and molecular mechanisms which could be interacting with gastroschisis predispositions within the first ten weeks of development.
Highlights
Gastroschisis constitutes one the leading categories of human birth defects concerning the ventral body wall development [1]
A total of 429 genes involving heterozygous DNA variations co-segregating with gastroschisis have been identified and selected from the whole exome sequencing (WES) gene list for further bioinformatic analyses [4]
Gene Ontology (GO) Consortium and Panther Classification System databases [5] identified several highly enriched GO terms (False Discovery Rates, FDR) within genes co-segregating in the family with recurrence for gastroschisis (Table 1)
Summary
Gastroschisis constitutes one the leading categories of human birth defects concerning the ventral body wall development [1]. Emerging evidence suggests that gastroschisis (an epidemiologic and pathogenetic dilemma) could be the consequence of a complex interplay of functionally interacting genetic and non-genetic factors as precipitating elements in its pathogenesis [2,3,4]. These influences have shown to be involved in several crucial biological processes such as blood vessel and epithelium development, cell adhesion, regulation of cytokine biosynthetic process, and regulation of developmental gene expression [2,3,4]. It may provide plausible clues to the closure of the ventral body wall
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
