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BMC Med Genet. 2016 Jul 15;17(1):44. doi: 10.1186/s12881-016-0311-5.

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

Author information

1
Department of Genetics, University of Leicester, Leicester, UK.
2
UCL Institute of Ophthalmology, University College London, London, UK.
3
UCL Genetics Institute, University College London, London, UK.
4
Moorfields Eye Hospital, London, UK.
5
Department of Medical Genetics, University of Cambridge, Cambridge, UK.
6
Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.
7
Department of Ophthalmology, Royal Perth Hospital, Perth, Australia.
8
Department of Ophthamology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
9
Department of Ophthalmology UCSF Medical School, San Francisco, USA.
10
Department of Genetics, University of Leicester, Leicester, UK. ejh33@le.ac.uk.

Abstract

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.

PMID:
27416785
PMCID:
PMC4946147
DOI:
10.1186/s12881-016-0311-5
[Indexed for MEDLINE]
Free PMC Article

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