Analysis of copy number variation at DMBT1 and age-related macular degeneration

S. Polley, V. Cipriani, Jane C. Khan, H. Shahid, A.T. Moore, J.R.W. Yates, E.J. Hollox

Research output: Contribution to journalArticle

Abstract

© 2016 The Author(s).Background: DMBT1 is a gene that shows extensive copy number variation (CNV) that alters the number of bacteria-binding domains in the protein and has been shown to activate the complement pathway. It lies next to the ARMS2/HTRA1 genes in a region of chromosome 10q26, where single nucleotide variants have been strongly associated with age-related macular degeneration (AMD), the commonest cause of blindness in Western populations. Complement activation is thought to be a key factor in the pathogenesis of this condition. We sought to investigate whether DMBT1 CNV plays any role in the susceptibility to AMD. Methods: We analysed long-range linkage disequilibrium of DMBT1 CNV1 and CNV2 with flanking single nucleotide polymorphisms (SNPs) using our previously published CNV and HapMap Phase 3 SNP data in the CEPH Europeans from Utah (CEU). We then typed a large cohort of 860 AMD patients and 419 examined age-matched controls for copy number at DMBT1 CNV1 and CNV2 and combined these data with copy numbers from a further 480 unexamined controls. Results: We found weak linkage disequilibrium between DMBT1 CNV1 and CNV2 with the SNPs rs1474526 and rs714816 in the HTRA1/ARMS2 region. By directly analysing copy number variation, we found no evidence of association of CNV1 or CNV2 with AMD. Conclusions: We have shown that copy number variation at DMBT1 does not affect risk of developing age-related macular degeneration and can therefore be ruled out from future studies investigating the association of structural variation at 10q26 with AMD.
Original languageEnglish
Article number44
JournalBMC Medical Genetics
Volume17
Issue number1
DOIs
Publication statusPublished - 2016

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Macular Degeneration
Single Nucleotide Polymorphism
Linkage Disequilibrium
HapMap Project
Complement Activation
Blindness
Genes
Nucleotides
Chromosomes
Bacteria
Population

Cite this

Polley, S., Cipriani, V., Khan, J. C., Shahid, H., Moore, A. T., Yates, J. R. W., & Hollox, E. J. (2016). Analysis of copy number variation at DMBT1 and age-related macular degeneration. BMC Medical Genetics, 17(1), [44]. https://doi.org/10.1186/s12881-016-0311-5
Polley, S. ; Cipriani, V. ; Khan, Jane C. ; Shahid, H. ; Moore, A.T. ; Yates, J.R.W. ; Hollox, E.J. / Analysis of copy number variation at DMBT1 and age-related macular degeneration. In: BMC Medical Genetics. 2016 ; Vol. 17, No. 1.
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abstract = "{\circledC} 2016 The Author(s).Background: DMBT1 is a gene that shows extensive copy number variation (CNV) that alters the number of bacteria-binding domains in the protein and has been shown to activate the complement pathway. It lies next to the ARMS2/HTRA1 genes in a region of chromosome 10q26, where single nucleotide variants have been strongly associated with age-related macular degeneration (AMD), the commonest cause of blindness in Western populations. Complement activation is thought to be a key factor in the pathogenesis of this condition. We sought to investigate whether DMBT1 CNV plays any role in the susceptibility to AMD. Methods: We analysed long-range linkage disequilibrium of DMBT1 CNV1 and CNV2 with flanking single nucleotide polymorphisms (SNPs) using our previously published CNV and HapMap Phase 3 SNP data in the CEPH Europeans from Utah (CEU). We then typed a large cohort of 860 AMD patients and 419 examined age-matched controls for copy number at DMBT1 CNV1 and CNV2 and combined these data with copy numbers from a further 480 unexamined controls. Results: We found weak linkage disequilibrium between DMBT1 CNV1 and CNV2 with the SNPs rs1474526 and rs714816 in the HTRA1/ARMS2 region. By directly analysing copy number variation, we found no evidence of association of CNV1 or CNV2 with AMD. Conclusions: We have shown that copy number variation at DMBT1 does not affect risk of developing age-related macular degeneration and can therefore be ruled out from future studies investigating the association of structural variation at 10q26 with AMD.",
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Polley, S, Cipriani, V, Khan, JC, Shahid, H, Moore, AT, Yates, JRW & Hollox, EJ 2016, 'Analysis of copy number variation at DMBT1 and age-related macular degeneration' BMC Medical Genetics, vol. 17, no. 1, 44. https://doi.org/10.1186/s12881-016-0311-5

Analysis of copy number variation at DMBT1 and age-related macular degeneration. / Polley, S.; Cipriani, V.; Khan, Jane C.; Shahid, H.; Moore, A.T.; Yates, J.R.W.; Hollox, E.J.

In: BMC Medical Genetics, Vol. 17, No. 1, 44, 2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Analysis of copy number variation at DMBT1 and age-related macular degeneration

AU - Polley, S.

AU - Cipriani, V.

AU - Khan, Jane C.

AU - Shahid, H.

AU - Moore, A.T.

AU - Yates, J.R.W.

AU - Hollox, E.J.

PY - 2016

Y1 - 2016

N2 - © 2016 The Author(s).Background: DMBT1 is a gene that shows extensive copy number variation (CNV) that alters the number of bacteria-binding domains in the protein and has been shown to activate the complement pathway. It lies next to the ARMS2/HTRA1 genes in a region of chromosome 10q26, where single nucleotide variants have been strongly associated with age-related macular degeneration (AMD), the commonest cause of blindness in Western populations. Complement activation is thought to be a key factor in the pathogenesis of this condition. We sought to investigate whether DMBT1 CNV plays any role in the susceptibility to AMD. Methods: We analysed long-range linkage disequilibrium of DMBT1 CNV1 and CNV2 with flanking single nucleotide polymorphisms (SNPs) using our previously published CNV and HapMap Phase 3 SNP data in the CEPH Europeans from Utah (CEU). We then typed a large cohort of 860 AMD patients and 419 examined age-matched controls for copy number at DMBT1 CNV1 and CNV2 and combined these data with copy numbers from a further 480 unexamined controls. Results: We found weak linkage disequilibrium between DMBT1 CNV1 and CNV2 with the SNPs rs1474526 and rs714816 in the HTRA1/ARMS2 region. By directly analysing copy number variation, we found no evidence of association of CNV1 or CNV2 with AMD. Conclusions: We have shown that copy number variation at DMBT1 does not affect risk of developing age-related macular degeneration and can therefore be ruled out from future studies investigating the association of structural variation at 10q26 with AMD.

AB - © 2016 The Author(s).Background: DMBT1 is a gene that shows extensive copy number variation (CNV) that alters the number of bacteria-binding domains in the protein and has been shown to activate the complement pathway. It lies next to the ARMS2/HTRA1 genes in a region of chromosome 10q26, where single nucleotide variants have been strongly associated with age-related macular degeneration (AMD), the commonest cause of blindness in Western populations. Complement activation is thought to be a key factor in the pathogenesis of this condition. We sought to investigate whether DMBT1 CNV plays any role in the susceptibility to AMD. Methods: We analysed long-range linkage disequilibrium of DMBT1 CNV1 and CNV2 with flanking single nucleotide polymorphisms (SNPs) using our previously published CNV and HapMap Phase 3 SNP data in the CEPH Europeans from Utah (CEU). We then typed a large cohort of 860 AMD patients and 419 examined age-matched controls for copy number at DMBT1 CNV1 and CNV2 and combined these data with copy numbers from a further 480 unexamined controls. Results: We found weak linkage disequilibrium between DMBT1 CNV1 and CNV2 with the SNPs rs1474526 and rs714816 in the HTRA1/ARMS2 region. By directly analysing copy number variation, we found no evidence of association of CNV1 or CNV2 with AMD. Conclusions: We have shown that copy number variation at DMBT1 does not affect risk of developing age-related macular degeneration and can therefore be ruled out from future studies investigating the association of structural variation at 10q26 with AMD.

U2 - 10.1186/s12881-016-0311-5

DO - 10.1186/s12881-016-0311-5

M3 - Article

VL - 17

JO - BMC Medical Genetics

JF - BMC Medical Genetics

SN - 1471-2350

IS - 1

M1 - 44

ER -