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Gene Network Analysis of Candidate Loci for Human Anorectal Malformations

Anorectal malformations (ARMs) are birth defects that require surgery and carry significant chronic morbidity. Our earlier genome-wide copy number variation (CNV) study had provided a wealth of candidate loci. To find out whether these candidate loci are related to important developmental pathways,...

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Autores principales: Wong, Emily H. M., Ng, Chun-Laam, Lui, Vincent Chi-Hang, So, Man-ting, Cherny, Stacey S., Sham, Pak-Chung, Tam, Paul Kwong-Hang, Garcia-Barceló, Maria-Mercè
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731316/
https://www.ncbi.nlm.nih.gov/pubmed/23936318
http://dx.doi.org/10.1371/journal.pone.0069142
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author Wong, Emily H. M.
Ng, Chun-Laam
Lui, Vincent Chi-Hang
So, Man-ting
Cherny, Stacey S.
Sham, Pak-Chung
Tam, Paul Kwong-Hang
Garcia-Barceló, Maria-Mercè
author_facet Wong, Emily H. M.
Ng, Chun-Laam
Lui, Vincent Chi-Hang
So, Man-ting
Cherny, Stacey S.
Sham, Pak-Chung
Tam, Paul Kwong-Hang
Garcia-Barceló, Maria-Mercè
author_sort Wong, Emily H. M.
collection PubMed
description Anorectal malformations (ARMs) are birth defects that require surgery and carry significant chronic morbidity. Our earlier genome-wide copy number variation (CNV) study had provided a wealth of candidate loci. To find out whether these candidate loci are related to important developmental pathways, we have performed an extensive literature search coupled with the currently available bioinformatics tools. This has allowed us to assign both genic and non-genic CNVs to interrelated pathways known to govern the development of the anorectal region. We have linked 11 candidate genes to the WNT signalling pathway and 17 genes to the cytoskeletal network. Interestingly, candidate genes with similar functions are disrupted by the same type of CNV. The gene network we discovered provides evidence that rare mutations in different interrelated genes may lead to similar phenotypes, accounting for genetic heterogeneity in ARMs. Classification of patients according to the affected pathway and lesion type should eventually improve the diagnosis and the identification of common genes/molecules as therapeutic targets.
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spelling pubmed-37313162013-08-09 Gene Network Analysis of Candidate Loci for Human Anorectal Malformations Wong, Emily H. M. Ng, Chun-Laam Lui, Vincent Chi-Hang So, Man-ting Cherny, Stacey S. Sham, Pak-Chung Tam, Paul Kwong-Hang Garcia-Barceló, Maria-Mercè PLoS One Research Article Anorectal malformations (ARMs) are birth defects that require surgery and carry significant chronic morbidity. Our earlier genome-wide copy number variation (CNV) study had provided a wealth of candidate loci. To find out whether these candidate loci are related to important developmental pathways, we have performed an extensive literature search coupled with the currently available bioinformatics tools. This has allowed us to assign both genic and non-genic CNVs to interrelated pathways known to govern the development of the anorectal region. We have linked 11 candidate genes to the WNT signalling pathway and 17 genes to the cytoskeletal network. Interestingly, candidate genes with similar functions are disrupted by the same type of CNV. The gene network we discovered provides evidence that rare mutations in different interrelated genes may lead to similar phenotypes, accounting for genetic heterogeneity in ARMs. Classification of patients according to the affected pathway and lesion type should eventually improve the diagnosis and the identification of common genes/molecules as therapeutic targets. Public Library of Science 2013-08-01 /pmc/articles/PMC3731316/ /pubmed/23936318 http://dx.doi.org/10.1371/journal.pone.0069142 Text en © 2013 Wong et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wong, Emily H. M.
Ng, Chun-Laam
Lui, Vincent Chi-Hang
So, Man-ting
Cherny, Stacey S.
Sham, Pak-Chung
Tam, Paul Kwong-Hang
Garcia-Barceló, Maria-Mercè
Gene Network Analysis of Candidate Loci for Human Anorectal Malformations
title Gene Network Analysis of Candidate Loci for Human Anorectal Malformations
title_full Gene Network Analysis of Candidate Loci for Human Anorectal Malformations
title_fullStr Gene Network Analysis of Candidate Loci for Human Anorectal Malformations
title_full_unstemmed Gene Network Analysis of Candidate Loci for Human Anorectal Malformations
title_short Gene Network Analysis of Candidate Loci for Human Anorectal Malformations
title_sort gene network analysis of candidate loci for human anorectal malformations
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731316/
https://www.ncbi.nlm.nih.gov/pubmed/23936318
http://dx.doi.org/10.1371/journal.pone.0069142
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