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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere0220617
JournalPloS one
Volume14
Issue number8
DOIs
StatePublished - Jan 1 2019

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DNA Copy Number Variations
urinary tract diseases
Vesico-Ureteral Reflux
Urinary Tract Infections
Genes
DNA
comparative genomic hybridization
genes
Comparative Genomic Hybridization
Ports and harbors
loci
Medicine
Ontology
linkage (genetics)
medicine
risk factors
Gene Ontology
genomics
genetic variation
Clinical Medicine

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Liang, D., McHugh, K. M., Brophy, P. D., Shaikh, N., Manak, J. R., Andrews, P., ... Hains, D. S. (2019). DNA copy number variations in children with vesicoureteral reflux and urinary tract infections. PloS one, 14(8), [e0220617]. https://doi.org/10.1371/journal.pone.0220617

DNA copy number variations in children with vesicoureteral reflux and urinary tract infections. / Liang, Dong; McHugh, Kirk M.; Brophy, Pat D.; Shaikh, Nader; Manak, J. Robert; Andrews, Peter; Hakker, Inessa; Wang, Zihua; Schwaderer, Andrew L.; Hains, David S.

In: PloS one, Vol. 14, No. 8, e0220617, 01.01.2019.

Research output: Contribution to journalArticle

Liang, D, McHugh, KM, Brophy, PD, Shaikh, N, Manak, JR, Andrews, P, Hakker, I, Wang, Z, Schwaderer, AL & Hains, DS 2019, 'DNA copy number variations in children with vesicoureteral reflux and urinary tract infections', PloS one, vol. 14, no. 8, e0220617. https://doi.org/10.1371/journal.pone.0220617
Liang D, McHugh KM, Brophy PD, Shaikh N, Manak JR, Andrews P et al. DNA copy number variations in children with vesicoureteral reflux and urinary tract infections. PloS one. 2019 Jan 1;14(8). e0220617. https://doi.org/10.1371/journal.pone.0220617
Liang, Dong ; McHugh, Kirk M. ; Brophy, Pat D. ; Shaikh, Nader ; Manak, J. Robert ; Andrews, Peter ; Hakker, Inessa ; Wang, Zihua ; Schwaderer, Andrew L. ; Hains, David S. / DNA copy number variations in children with vesicoureteral reflux and urinary tract infections. In: PloS one. 2019 ; Vol. 14, No. 8.
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