Comprehensive analysis of Copy Number Variation of genes at chromosome 1 and 10 loci associated with late age related macular degeneration.

Copy Number Variants (CNVs) are now recognized as playing a significant role in complex disease etiology. Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the western world. While a number of genes and environmental factors have been associated with both...

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Autores principales:	Stuart Cantsilieris, Stefan J White, Andrea J Richardson, Robyn H Guymer, Paul N Baird
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7fefbd834efd40919740412dd0db20fd
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spelling	oai:doaj.org-article:7fefbd834efd40919740412dd0db20fd2021-11-18T07:21:00ZComprehensive analysis of Copy Number Variation of genes at chromosome 1 and 10 loci associated with late age related macular degeneration.1932-620310.1371/journal.pone.0035255https://doaj.org/article/7fefbd834efd40919740412dd0db20fd2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22558131/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Copy Number Variants (CNVs) are now recognized as playing a significant role in complex disease etiology. Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the western world. While a number of genes and environmental factors have been associated with both risk and protection in AMD, the role of CNVs has remained largely unexplored. We analyzed the two major AMD risk-associated regions on chromosome 1q32 and 10q26 for CNVs using Multiplex Ligation-dependant Probe Amplification. The analysis targeted nine genes in these two key regions, including the Complement Factor H (CFH) gene, the 5 CFH-related (CFHR) genes representing a known copy number "hotspot", the F13B gene as well as the ARMS2 and HTRA1 genes in 387 cases of late AMD and 327 controls. No copy number variation was detected at the ARMS2 and HTRA1 genes in the chromosome 10 region, nor for the CFH and F13B genes at the chromosome 1 region. However, significant association was identified for the CFHR3-1 deletion in AMD cases (p = 2.38 × 10(-12)) OR = 0.31, CI-0.95 (0.23-0.44), for both neovascular disease (nAMD) (p = 8.3 × 10(-9)) OR = 0.36 CI-0.95 (0.25-0.52) and geographic atrophy (GA) (p = 1.5 × 10(-6)) OR = 0.36 CI-0.95 (0.25-0.52) compared to controls. In addition, a significant association with deletion of CFHR1-4 was identified only in patients who presented with bilateral GA (p = 0.02) (OR = 7.6 CI-0.95 1.38-41.8). This is the first report of a phenotype specific association of a CNV for a major subtype of AMD and potentially allows for pre-diagnostic identification of individuals most likely to proceed to this end stage of disease.Stuart CantsilierisStefan J WhiteAndrea J RichardsonRobyn H GuymerPaul N BairdPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35255 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stuart Cantsilieris Stefan J White Andrea J Richardson Robyn H Guymer Paul N Baird Comprehensive analysis of Copy Number Variation of genes at chromosome 1 and 10 loci associated with late age related macular degeneration.
description	Copy Number Variants (CNVs) are now recognized as playing a significant role in complex disease etiology. Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the western world. While a number of genes and environmental factors have been associated with both risk and protection in AMD, the role of CNVs has remained largely unexplored. We analyzed the two major AMD risk-associated regions on chromosome 1q32 and 10q26 for CNVs using Multiplex Ligation-dependant Probe Amplification. The analysis targeted nine genes in these two key regions, including the Complement Factor H (CFH) gene, the 5 CFH-related (CFHR) genes representing a known copy number "hotspot", the F13B gene as well as the ARMS2 and HTRA1 genes in 387 cases of late AMD and 327 controls. No copy number variation was detected at the ARMS2 and HTRA1 genes in the chromosome 10 region, nor for the CFH and F13B genes at the chromosome 1 region. However, significant association was identified for the CFHR3-1 deletion in AMD cases (p = 2.38 × 10(-12)) OR = 0.31, CI-0.95 (0.23-0.44), for both neovascular disease (nAMD) (p = 8.3 × 10(-9)) OR = 0.36 CI-0.95 (0.25-0.52) and geographic atrophy (GA) (p = 1.5 × 10(-6)) OR = 0.36 CI-0.95 (0.25-0.52) compared to controls. In addition, a significant association with deletion of CFHR1-4 was identified only in patients who presented with bilateral GA (p = 0.02) (OR = 7.6 CI-0.95 1.38-41.8). This is the first report of a phenotype specific association of a CNV for a major subtype of AMD and potentially allows for pre-diagnostic identification of individuals most likely to proceed to this end stage of disease.
format	article
author	Stuart Cantsilieris Stefan J White Andrea J Richardson Robyn H Guymer Paul N Baird
author_facet	Stuart Cantsilieris Stefan J White Andrea J Richardson Robyn H Guymer Paul N Baird
author_sort	Stuart Cantsilieris
title	Comprehensive analysis of Copy Number Variation of genes at chromosome 1 and 10 loci associated with late age related macular degeneration.
title_short	Comprehensive analysis of Copy Number Variation of genes at chromosome 1 and 10 loci associated with late age related macular degeneration.
title_full	Comprehensive analysis of Copy Number Variation of genes at chromosome 1 and 10 loci associated with late age related macular degeneration.
title_fullStr	Comprehensive analysis of Copy Number Variation of genes at chromosome 1 and 10 loci associated with late age related macular degeneration.
title_full_unstemmed	Comprehensive analysis of Copy Number Variation of genes at chromosome 1 and 10 loci associated with late age related macular degeneration.
title_sort	comprehensive analysis of copy number variation of genes at chromosome 1 and 10 loci associated with late age related macular degeneration.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/7fefbd834efd40919740412dd0db20fd
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Comprehensive analysis of Copy Number Variation of genes at chromosome 1 and 10 loci associated with late age related macular degeneration.

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