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Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism

BACKGROUND: Copy number variation (CNV) is a potential contributing factor to many genetic diseases. Here we investigated the potential association of CNV with nonsyndromic cryptorchidism, the most common male congenital genitourinary defect, in a Caucasian population. METHODS: Genome wide genotypin...

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Autores principales: Wang, Yanping, Li, Jin, Kolon, Thomas F., Olivant Fisher, Alicia, Figueroa, T. Ernesto, BaniHani, Ahmad H., Hagerty, Jennifer A., Gonzalez, Ricardo, Noh, Paul H., Chiavacci, Rosetta M., Harden, Kisha R., Abrams, Debra J., Stabley, Deborah, Kim, Cecilia E., Sol-Church, Katia, Hakonarson, Hakon, Devoto, Marcella, Barthold, Julia Spencer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073740/
https://www.ncbi.nlm.nih.gov/pubmed/27769252
http://dx.doi.org/10.1186/s12894-016-0180-4
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author Wang, Yanping
Li, Jin
Kolon, Thomas F.
Olivant Fisher, Alicia
Figueroa, T. Ernesto
BaniHani, Ahmad H.
Hagerty, Jennifer A.
Gonzalez, Ricardo
Noh, Paul H.
Chiavacci, Rosetta M.
Harden, Kisha R.
Abrams, Debra J.
Stabley, Deborah
Kim, Cecilia E.
Sol-Church, Katia
Hakonarson, Hakon
Devoto, Marcella
Barthold, Julia Spencer
author_facet Wang, Yanping
Li, Jin
Kolon, Thomas F.
Olivant Fisher, Alicia
Figueroa, T. Ernesto
BaniHani, Ahmad H.
Hagerty, Jennifer A.
Gonzalez, Ricardo
Noh, Paul H.
Chiavacci, Rosetta M.
Harden, Kisha R.
Abrams, Debra J.
Stabley, Deborah
Kim, Cecilia E.
Sol-Church, Katia
Hakonarson, Hakon
Devoto, Marcella
Barthold, Julia Spencer
author_sort Wang, Yanping
collection PubMed
description BACKGROUND: Copy number variation (CNV) is a potential contributing factor to many genetic diseases. Here we investigated the potential association of CNV with nonsyndromic cryptorchidism, the most common male congenital genitourinary defect, in a Caucasian population. METHODS: Genome wide genotyping were performed in 559 cases and 1772 controls (Group 1) using Illumina HumanHap550 v1, HumanHap550 v3 or Human610-Quad platforms and in 353 cases and 1149 controls (Group 2) using the Illumina Human OmniExpress 12v1 or Human OmniExpress 12v1-1. Signal intensity data including log R ratio (LRR) and B allele frequency (BAF) for each single nucleotide polymorphism (SNP) were used for CNV detection using PennCNV software. After sample quality control, gene- and CNV-based association tests were performed using cleaned data from Group 1 (493 cases and 1586 controls) and Group 2 (307 cases and 1102 controls) using ParseCNV software. Meta-analysis was performed using gene-based test results as input to identify significant genes, and CNVs in or around significant genes were identified in CNV-based association test results. Called CNVs passing quality control and signal intensity visualization examination were considered for validation using TaqMan CNV assays and QuantStudio® 3D Digital PCR System. RESULTS: The meta-analysis identified 373 genome wide significant (p < 5X10(−4)) genes/loci including 49 genes/loci with deletions and 324 with duplications. Among them, 17 genes with deletion and 1 gene with duplication were identified in CNV-based association results in both Group 1 and Group 2. Only 2 genes (NUCB2 and UPF2) containing deletions passed CNV quality control in both groups and signal intensity visualization examination, but laboratory validation failed to verify these deletions. CONCLUSIONS: Our data do not support that structural variation is a major cause of nonsyndromic cryptorchidism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12894-016-0180-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-50737402016-10-24 Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism Wang, Yanping Li, Jin Kolon, Thomas F. Olivant Fisher, Alicia Figueroa, T. Ernesto BaniHani, Ahmad H. Hagerty, Jennifer A. Gonzalez, Ricardo Noh, Paul H. Chiavacci, Rosetta M. Harden, Kisha R. Abrams, Debra J. Stabley, Deborah Kim, Cecilia E. Sol-Church, Katia Hakonarson, Hakon Devoto, Marcella Barthold, Julia Spencer BMC Urol Research Article BACKGROUND: Copy number variation (CNV) is a potential contributing factor to many genetic diseases. Here we investigated the potential association of CNV with nonsyndromic cryptorchidism, the most common male congenital genitourinary defect, in a Caucasian population. METHODS: Genome wide genotyping were performed in 559 cases and 1772 controls (Group 1) using Illumina HumanHap550 v1, HumanHap550 v3 or Human610-Quad platforms and in 353 cases and 1149 controls (Group 2) using the Illumina Human OmniExpress 12v1 or Human OmniExpress 12v1-1. Signal intensity data including log R ratio (LRR) and B allele frequency (BAF) for each single nucleotide polymorphism (SNP) were used for CNV detection using PennCNV software. After sample quality control, gene- and CNV-based association tests were performed using cleaned data from Group 1 (493 cases and 1586 controls) and Group 2 (307 cases and 1102 controls) using ParseCNV software. Meta-analysis was performed using gene-based test results as input to identify significant genes, and CNVs in or around significant genes were identified in CNV-based association test results. Called CNVs passing quality control and signal intensity visualization examination were considered for validation using TaqMan CNV assays and QuantStudio® 3D Digital PCR System. RESULTS: The meta-analysis identified 373 genome wide significant (p < 5X10(−4)) genes/loci including 49 genes/loci with deletions and 324 with duplications. Among them, 17 genes with deletion and 1 gene with duplication were identified in CNV-based association results in both Group 1 and Group 2. Only 2 genes (NUCB2 and UPF2) containing deletions passed CNV quality control in both groups and signal intensity visualization examination, but laboratory validation failed to verify these deletions. CONCLUSIONS: Our data do not support that structural variation is a major cause of nonsyndromic cryptorchidism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12894-016-0180-4) contains supplementary material, which is available to authorized users. BioMed Central 2016-10-21 /pmc/articles/PMC5073740/ /pubmed/27769252 http://dx.doi.org/10.1186/s12894-016-0180-4 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Wang, Yanping
Li, Jin
Kolon, Thomas F.
Olivant Fisher, Alicia
Figueroa, T. Ernesto
BaniHani, Ahmad H.
Hagerty, Jennifer A.
Gonzalez, Ricardo
Noh, Paul H.
Chiavacci, Rosetta M.
Harden, Kisha R.
Abrams, Debra J.
Stabley, Deborah
Kim, Cecilia E.
Sol-Church, Katia
Hakonarson, Hakon
Devoto, Marcella
Barthold, Julia Spencer
Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism
title Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism
title_full Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism
title_fullStr Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism
title_full_unstemmed Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism
title_short Genomic copy number variation association study in Caucasian patients with nonsyndromic cryptorchidism
title_sort genomic copy number variation association study in caucasian patients with nonsyndromic cryptorchidism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073740/
https://www.ncbi.nlm.nih.gov/pubmed/27769252
http://dx.doi.org/10.1186/s12894-016-0180-4
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