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UGT2B17 copy number gain in a large ankylosing spondylitis multiplex family

BACKGROUND: The primary objective of this study is to identify novel copy number variations (CNVs) associated with familial ankylosing spondylitis (AS). A customized genome-wide microarray was designed to detect CNVs and applied to a multiplex AS family with six (6) affected family members. CNVs wer...

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Autores principales: Uddin, Mohammed, Maksymowych, Walter P, Inman, Robert, Gladman, Dafna, Munn, Alexandra, Yazdani, Ramin, Pellett, Fawnda, Hamilton, Sean, O’Rielly, Darren D, Rahman, Proton
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751806/
https://www.ncbi.nlm.nih.gov/pubmed/23927372
http://dx.doi.org/10.1186/1471-2156-14-67
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author Uddin, Mohammed
Maksymowych, Walter P
Inman, Robert
Gladman, Dafna
Munn, Alexandra
Yazdani, Ramin
Pellett, Fawnda
Hamilton, Sean
O’Rielly, Darren D
Rahman, Proton
author_facet Uddin, Mohammed
Maksymowych, Walter P
Inman, Robert
Gladman, Dafna
Munn, Alexandra
Yazdani, Ramin
Pellett, Fawnda
Hamilton, Sean
O’Rielly, Darren D
Rahman, Proton
author_sort Uddin, Mohammed
collection PubMed
description BACKGROUND: The primary objective of this study is to identify novel copy number variations (CNVs) associated with familial ankylosing spondylitis (AS). A customized genome-wide microarray was designed to detect CNVs and applied to a multiplex AS family with six (6) affected family members. CNVs were detected using the built-in DNA analytics aberration detection method-2 (ADM-2) algorithm. Gene enrichment analysis was performed to observe the segregation. Subsequent validation was performed using real time quantitative fluorescence polymerase reaction (QF-PCR). The frequency of copy number variation for the UGT2B17 gene was then performed on two well-defined AS cohorts. Fisher exact test was performed to quantify the association. RESULTS: Our family-based analysis revealed ten gene-enriched CNVs that segregate with all six family members affected with AS. Based on the proposed function and the polymorphic nature of the UGT2B17 gene, the UGT2B17 gene CNV was selected for validation using real time QF-PCR with full concordance. The frequency of two copies of the UGT2B17 gene CNV was 0.41 in the Newfoundland AS cases and 0.35 in the Newfoundland controls (OR = 1.26(0.99-1.59); p < 0.05)), whereas the frequency of two (2) copies of the UGT2B17 gene CNV was 0.40 in the Alberta AS cases and 0.39 in the Alberta controls (OR = 1.05(95% CI: 0.83-1.33); p < 0.71)). CONCLUSIONS: A genome-wide microarray interrogation of a large multiplex AS family revealed segregation of the UGT2B17 gene CNV among all affected family members. The association of the UGT2B17 CNV with AS is particularly interesting given the recent association of this CNV with osteoporosis and the proposed function as it encodes a key enzyme that inhibits androgens. However, two copies of the UGT2B17 gene CNV were only marginally significant in a uniplex AS cohort from Newfoundland but not in a uniplex AS cohort from Alberta.
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spelling pubmed-37518062013-08-24 UGT2B17 copy number gain in a large ankylosing spondylitis multiplex family Uddin, Mohammed Maksymowych, Walter P Inman, Robert Gladman, Dafna Munn, Alexandra Yazdani, Ramin Pellett, Fawnda Hamilton, Sean O’Rielly, Darren D Rahman, Proton BMC Genet Research Article BACKGROUND: The primary objective of this study is to identify novel copy number variations (CNVs) associated with familial ankylosing spondylitis (AS). A customized genome-wide microarray was designed to detect CNVs and applied to a multiplex AS family with six (6) affected family members. CNVs were detected using the built-in DNA analytics aberration detection method-2 (ADM-2) algorithm. Gene enrichment analysis was performed to observe the segregation. Subsequent validation was performed using real time quantitative fluorescence polymerase reaction (QF-PCR). The frequency of copy number variation for the UGT2B17 gene was then performed on two well-defined AS cohorts. Fisher exact test was performed to quantify the association. RESULTS: Our family-based analysis revealed ten gene-enriched CNVs that segregate with all six family members affected with AS. Based on the proposed function and the polymorphic nature of the UGT2B17 gene, the UGT2B17 gene CNV was selected for validation using real time QF-PCR with full concordance. The frequency of two copies of the UGT2B17 gene CNV was 0.41 in the Newfoundland AS cases and 0.35 in the Newfoundland controls (OR = 1.26(0.99-1.59); p < 0.05)), whereas the frequency of two (2) copies of the UGT2B17 gene CNV was 0.40 in the Alberta AS cases and 0.39 in the Alberta controls (OR = 1.05(95% CI: 0.83-1.33); p < 0.71)). CONCLUSIONS: A genome-wide microarray interrogation of a large multiplex AS family revealed segregation of the UGT2B17 gene CNV among all affected family members. The association of the UGT2B17 CNV with AS is particularly interesting given the recent association of this CNV with osteoporosis and the proposed function as it encodes a key enzyme that inhibits androgens. However, two copies of the UGT2B17 gene CNV were only marginally significant in a uniplex AS cohort from Newfoundland but not in a uniplex AS cohort from Alberta. BioMed Central 2013-08-08 /pmc/articles/PMC3751806/ /pubmed/23927372 http://dx.doi.org/10.1186/1471-2156-14-67 Text en Copyright © 2013 Uddin et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Uddin, Mohammed
Maksymowych, Walter P
Inman, Robert
Gladman, Dafna
Munn, Alexandra
Yazdani, Ramin
Pellett, Fawnda
Hamilton, Sean
O’Rielly, Darren D
Rahman, Proton
UGT2B17 copy number gain in a large ankylosing spondylitis multiplex family
title UGT2B17 copy number gain in a large ankylosing spondylitis multiplex family
title_full UGT2B17 copy number gain in a large ankylosing spondylitis multiplex family
title_fullStr UGT2B17 copy number gain in a large ankylosing spondylitis multiplex family
title_full_unstemmed UGT2B17 copy number gain in a large ankylosing spondylitis multiplex family
title_short UGT2B17 copy number gain in a large ankylosing spondylitis multiplex family
title_sort ugt2b17 copy number gain in a large ankylosing spondylitis multiplex family
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3751806/
https://www.ncbi.nlm.nih.gov/pubmed/23927372
http://dx.doi.org/10.1186/1471-2156-14-67
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