Bioinformatic Analysis of Gene Variants from Gastroschisis Recurrence Identifies Multiple Novel Pathogenetic Pathways: Implication for the Closure of the Ventral Body Wall

SalinasTorres, Victor Michael y Gallardo Blanco, Hugo L. y Salinas Torres, Rafael A. y Cerda Flores, Ricardo M. y Lugo Trampe, Jose J. y Villarreal Martinez, Daniel Z. y Martinez de Villarreal, Laura E. (2019) Bioinformatic Analysis of Gene Variants from Gastroschisis Recurrence Identifies Multiple Novel Pathogenetic Pathways: Implication for the Closure of the Ventral Body Wall. International Journal of Molecular Sciences, 20 (9). p. 2295. ISSN 1422-0067

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URL o página oficial: https://www.mdpi.com/1422-0067/20/9/2295

Resumen

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 {UGT}1A3, {UGT}1A4, {UGT}1A5, {UGT}1A6, {UGT}1A7, {UGT}1A8, {UGT}1A9, {UGT}1A10, {AOX}1, {NOTCH}1, {HIST}1H2BB, {RPS}3, {THBS}1, {ADCY}9, and {FGFR}4. {SVS}-{PhoRank} identified a dominant model in {OR}10G4 (also as heterozygous de novo), {ITIH}3, {PLEKHG}4B, {SLC}9A3, {ITGA}2, {AOX}1, and {ALPP}, including a recessive model in {UGT}1A7, {UGT}1A6, {PER}2, {PTPRD}, and {UGT}1A3. A heterozygous compound model was observed in {CDYL}, {KDM}5A, {RASGRP}1, {MYBPC}2, {PDE}4DIP, F5, {OBSCN}, and {UGT}1A. 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.

Tipo de elemento:

Article

Palabras claves no controlados:

Abdominal wall defect, Alleles, Bioinformatics, Development, Gastroschisis, Genes, Genetics, Pathogenesis, Recurrence, Whole exome sequencing

Materias:

CONACYT > Biología y Química
CONACYT > Medicina y Ciencias de la Salud

Divisiones:

Medicina > Maestría en Ciencias con Orientación en Biología Molecular e Ingeniería Genética

Usuario depositante:

Dr.C. Hugo Gallardo Blanco

Creadores:

Creador	Email	ORCID
SalinasTorres, Victor Michael	NO ESPECIFICADO	NO ESPECIFICADO
Gallardo Blanco, Hugo L.	hugo.gallardobl@uanl.edu.mx	orcid.org/0000-0002-7816-4967
Salinas Torres, Rafael A.	NO ESPECIFICADO	NO ESPECIFICADO
Cerda Flores, Ricardo M.	NO ESPECIFICADO	NO ESPECIFICADO
Lugo Trampe, Jose J.	NO ESPECIFICADO	NO ESPECIFICADO
Villarreal Martinez, Daniel Z.	NO ESPECIFICADO	NO ESPECIFICADO
Martinez de Villarreal, Laura E.	NO ESPECIFICADO	NO ESPECIFICADO