DNA copy number variations in children with vesicoureteral reflux and urinary tract infections

Dong Liang; Kirk M McHugh; Pat D Brophy; Nader Shaikh; J Robert Manak; Peter Andrews; Inessa Hakker; Zihua Wang; Andrew L Schwaderer; David S Hains

doi:10.1371/journal.pone.0220617

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DNA copy number variations in children with vesicoureteral reflux and urinary tract infections

Journal article

Open access

Peer reviewed

DNA copy number variations in children with vesicoureteral reflux and urinary tract infections

Dong Liang, Kirk M McHugh, Pat D Brophy, Nader Shaikh, J Robert Manak, Peter Andrews, Inessa Hakker, Zihua Wang, Andrew L Schwaderer and David S Hains

PloS one, Vol.14(8), e0220617

2019

DOI: 10.1371/journal.pone.0220617

PMCID: PMC6690579

PMID: 31404082

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Abstract

Vesicoureteral reflux (VUR) is a complex, heritable disorder. Genome-wide linkage analyses of families affected by VUR have revealed multiple genomic loci linked to VUR. These loci normally harbor a number of genes whose biologically functional variant is yet to be identified. DNA copy number variations (CNVs) have not been extensively studied at high resolution in VUR patients. In this study, we performed array comparative genomic hybridization (aCGH) on a cohort of patients with a history of both VUR and urinary tract infection (UTI) with the objective of identifying genetic variations responsible for VUR and/or UTI susceptibility. UTI/VUR-associated CNVs were identified by aCGH results from the 192 Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) patients compared to 683 controls. Rare, large CNVs that are likely pathogenic and lead to VUR development were identified using stringent analysis criteria. Because UTI is a common affliction with multiple risk factors, we utilized standard analysis to identify potential disease-modifying CNVs that can contribute to UTI risk. Gene ontology analysis identified that CNVs in innate immunity and development genes were enriched in RIVUR patients. CNVs affecting innate immune genes may contribute to UTI susceptibility in VUR patients and may provide the first step in assisting clinical medicine in determining adverse outcome risk in children with VUR.

Case-Control Studies

Child

DNA Copy Number Variations - genetics

Female

Genetic Linkage

Genetic Predisposition to Disease - genetics

Humans

Immunity, Innate - genetics

Male

Risk Factors

Urinary Tract Infections - genetics

Vesico-Ureteral Reflux - genetics

Details

Title: Subtitle: DNA copy number variations in children with vesicoureteral reflux and urinary tract infections
Creators: Dong Liang - Indiana University – Purdue University Indianapolis
Kirk M McHugh - Division of Anatomy, The Ohio State University, Columbus, OH, United States of America
Pat D Brophy - University of Rochester Medical Center
Nader Shaikh - Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, United States of America
J Robert Manak - University of Iowa, Biology
Peter Andrews - Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States of America
Inessa Hakker - Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States of America
Zihua Wang - Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States of America
Andrew L Schwaderer - Riley Hospital for Children at Indiana University Health, Indianapolis, IN, United States of America
David S Hains - Riley Hospital for Children at Indiana University Health, Indianapolis, IN, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.14(8), e0220617
DOI: 10.1371/journal.pone.0220617
PMID: 31404082
PMCID: PMC6690579
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: 1RC4DK090937-01; DOI: 10.13039/100000002, name: National Institutes of Health, award: 1RC4DK090937-01; DOI: 10.13039/100000002, name: National Institutes of Health, award: 1RC4DK090937-01; DOI: 10.13039/100000002, name: National Institutes of Health, award: 1RC4DK090937-01; DOI: 10.13039/100000002, name: National Institutes of Health, award: 1RC4DK090937-01; DOI: 10.13039/100000002, name: National Institutes of Health, award: 1RC4DK090937-01; DOI: 10.13039/100000002, name: National Institutes of Health, award: 1R01DK106286-01; DOI: 10.13039/100000002, name: National Institutes of Health, award: 1R01DK106286-01
Language: English
Date published: 2019
Academic Unit: Stead Family Department of Pediatrics; Biology; Craniofacial Anomalies Research Center
Record Identifier: 9984224760302771

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