DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma

Yutao Liu; Melanie E. Garrett; Brian L. Yaspan; Jessica Cooke Bailey; Stephanie J. Loomis; Murray Brilliant; Donald L. Budenz; William G. Christen; John H. Fingert; Douglas Gaasterland; Terry Gaasterland; Jae H. Kang; Richard K. Lee; Paul Lichter; Sayoko E. Moroi; Anthony Realini; Julia E. Richards; Joel S. Schuman; William K. Scott; Kuldev Singh; Arthur J. Sit; Douglas Vollrath; Robert Weinreb; Gadi Wollstein; Donald J. Zack; Kang Zhang; Margaret A. Pericak-Vance; Jonathan L. Haines; Louis R. Pasquale; Janey L. Wiggs; R. Rand Allingham; Allison E. Ashley-Koch; Michael A. Hauser

doi:10.1167/iovs.14-15712

DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma

Yutao Liu, Melanie E. Garrett, Brian L. Yaspan, Jessica Cooke Bailey, Stephanie J. Loomis, Murray Brilliant, Donald L. Budenz, William G. Christen, John H. Fingert, Douglas Gaasterland, Terry Gaasterland, Jae H. Kang, Richard K. Lee, Paul Lichter, Sayoko E. Moroi, Anthony Realini, Julia E. Richards, Joel S. Schuman, William K. Scott, Kuldev SinghArthur J. Sit, Douglas Vollrath, Robert Weinreb, Gadi Wollstein, Donald J. Zack, Kang Zhang, Margaret A. Pericak-Vance, Jonathan L. Haines, Louis R. Pasquale, Janey L. Wiggs, R. Rand Allingham, Allison E. Ashley-Koch, Michael A. Hauser

Cellular Biology and Anatomy

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

Purpose: We examined the role of DNA copy number variants (CNVs) of known glaucoma genes in relation to primary open angle glaucoma (POAG).

Methods: Our study included DNA samples from two studies (NEIGHBOR and GLAUGEN). All the samples were genotyped with the Illumina Human660W_Quad_v1 BeadChip. After removing non–blood-derived and amplified DNA samples, we applied quality control steps based on the mean Log R Ratio and the mean B allele frequency. Subsequently, data from 3057 DNA samples (1599 cases and 1458 controls) were analyzed with PennCNV software. We defined CNVs as those ≥5 kilobases (kb) in size and interrogated by ≥5 consecutive probes. We further limited our investigation to CNVs in known POAG-related genes, including CDKN2B-AS1, TMCO1, SIX1/SIX6, CAV1/CAV2, the LRP12-ZFPM2 region, GAS7, ATOH7, FNDC3B, CYP1B1, MYOC, OPTN, WDR36, SRBD1, TBK1, and GALC.

Results: Genomic duplications of CDKN2B-AS1 and TMCO1 were each found in a single case. Two cases carried duplications in the GAS7 region. Genomic deletions of SIX6 and ATOH7 were each identified in one case. One case carried a TBK1 deletion and another case carried a TBK1 duplication. No controls had duplications or deletions in these six genes. A single control had a duplication in the MYOC region. Deletions of GALC were observed in five cases and two controls.

Conclusions: The CNV analysis of a large set of cases and controls revealed the presence of rare CNVs in known POAG susceptibility genes. Our data suggest that these rare CNVs may contribute to POAG pathogenesis and merit functional evaluation.

Original language	English (US)
Pages (from-to)	8251-8258
Number of pages	8
Journal	Investigative Ophthalmology and Visual Science
Volume	55
Issue number	12
DOIs	https://doi.org/10.1167/iovs.14-15712
State	Published - Nov 20 2014

Keywords

DNA copy number variants
GAS7
Genetics
POAG
SIX6

ASJC Scopus subject areas

Ophthalmology
Sensory Systems
Cellular and Molecular Neuroscience

Access to Document

10.1167/iovs.14-15712

Cite this

Liu, Y., Garrett, M. E., Yaspan, B. L., Bailey, J. C., Loomis, S. J., Brilliant, M., Budenz, D. L., Christen, W. G., Fingert, J. H., Gaasterland, D., Gaasterland, T., Kang, J. H., Lee, R. K., Lichter, P., Moroi, S. E., Realini, A., Richards, J. E., Schuman, J. S., Scott, W. K., ... Hauser, M. A. (2014). DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma. Investigative Ophthalmology and Visual Science, 55(12), 8251-8258. https://doi.org/10.1167/iovs.14-15712

Liu, Y, Garrett, ME, Yaspan, BL, Bailey, JC, Loomis, SJ, Brilliant, M, Budenz, DL, Christen, WG, Fingert, JH, Gaasterland, D, Gaasterland, T, Kang, JH, Lee, RK, Lichter, P, Moroi, SE, Realini, A, Richards, JE, Schuman, JS, Scott, WK, Singh, K, Sit, AJ, Vollrath, D, Weinreb, R, Wollstein, G, Zack, DJ, Zhang, K, Pericak-Vance, MA, Haines, JL, Pasquale, LR, Wiggs, JL, Allingham, RR, Ashley-Koch, AE & Hauser, MA 2014, 'DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma', Investigative Ophthalmology and Visual Science, vol. 55, no. 12, pp. 8251-8258. https://doi.org/10.1167/iovs.14-15712

@article{27ee943eb3ee4ab1919771bf7d196186,

title = "DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma",

abstract = "Purpose: We examined the role of DNA copy number variants (CNVs) of known glaucoma genes in relation to primary open angle glaucoma (POAG).Methods: Our study included DNA samples from two studies (NEIGHBOR and GLAUGEN). All the samples were genotyped with the Illumina Human660W_Quad_v1 BeadChip. After removing non–blood-derived and amplified DNA samples, we applied quality control steps based on the mean Log R Ratio and the mean B allele frequency. Subsequently, data from 3057 DNA samples (1599 cases and 1458 controls) were analyzed with PennCNV software. We defined CNVs as those ≥5 kilobases (kb) in size and interrogated by ≥5 consecutive probes. We further limited our investigation to CNVs in known POAG-related genes, including CDKN2B-AS1, TMCO1, SIX1/SIX6, CAV1/CAV2, the LRP12-ZFPM2 region, GAS7, ATOH7, FNDC3B, CYP1B1, MYOC, OPTN, WDR36, SRBD1, TBK1, and GALC.Results: Genomic duplications of CDKN2B-AS1 and TMCO1 were each found in a single case. Two cases carried duplications in the GAS7 region. Genomic deletions of SIX6 and ATOH7 were each identified in one case. One case carried a TBK1 deletion and another case carried a TBK1 duplication. No controls had duplications or deletions in these six genes. A single control had a duplication in the MYOC region. Deletions of GALC were observed in five cases and two controls.Conclusions: The CNV analysis of a large set of cases and controls revealed the presence of rare CNVs in known POAG susceptibility genes. Our data suggest that these rare CNVs may contribute to POAG pathogenesis and merit functional evaluation.",

keywords = "DNA copy number variants, GAS7, Genetics, POAG, SIX6",

author = "Yutao Liu and Garrett, {Melanie E.} and Yaspan, {Brian L.} and Bailey, {Jessica Cooke} and Loomis, {Stephanie J.} and Murray Brilliant and Budenz, {Donald L.} and Christen, {William G.} and Fingert, {John H.} and Douglas Gaasterland and Terry Gaasterland and Kang, {Jae H.} and Lee, {Richard K.} and Paul Lichter and Moroi, {Sayoko E.} and Anthony Realini and Richards, {Julia E.} and Schuman, {Joel S.} and Scott, {William K.} and Kuldev Singh and Sit, {Arthur J.} and Douglas Vollrath and Robert Weinreb and Gadi Wollstein and Zack, {Donald J.} and Kang Zhang and Pericak-Vance, {Margaret A.} and Haines, {Jonathan L.} and Pasquale, {Louis R.} and Wiggs, {Janey L.} and Allingham, {R. Rand} and Ashley-Koch, {Allison E.} and Hauser, {Michael A.}",

note = "Publisher Copyright: {\textcopyright} 2014 The Association for Research in Vision and Ophthalmology, Inc.",

year = "2014",

month = nov,

day = "20",

doi = "10.1167/iovs.14-15712",

language = "English (US)",

volume = "55",

pages = "8251--8258",

journal = "Investigative Ophthalmology and Visual Science",

issn = "0146-0404",

publisher = "Association for Research in Vision and Ophthalmology Inc.",

number = "12",

}

TY - JOUR

T1 - DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma

AU - Liu, Yutao

AU - Garrett, Melanie E.

AU - Yaspan, Brian L.

AU - Bailey, Jessica Cooke

AU - Loomis, Stephanie J.

AU - Brilliant, Murray

AU - Budenz, Donald L.

AU - Christen, William G.

AU - Fingert, John H.

AU - Gaasterland, Douglas

AU - Gaasterland, Terry

AU - Kang, Jae H.

AU - Lee, Richard K.

AU - Lichter, Paul

AU - Moroi, Sayoko E.

AU - Realini, Anthony

AU - Richards, Julia E.

AU - Schuman, Joel S.

AU - Scott, William K.

AU - Singh, Kuldev

AU - Sit, Arthur J.

AU - Vollrath, Douglas

AU - Weinreb, Robert

AU - Wollstein, Gadi

AU - Zack, Donald J.

AU - Zhang, Kang

AU - Pericak-Vance, Margaret A.

AU - Haines, Jonathan L.

AU - Pasquale, Louis R.

AU - Wiggs, Janey L.

AU - Allingham, R. Rand

AU - Ashley-Koch, Allison E.

AU - Hauser, Michael A.

PY - 2014/11/20

Y1 - 2014/11/20

N2 - Purpose: We examined the role of DNA copy number variants (CNVs) of known glaucoma genes in relation to primary open angle glaucoma (POAG).Methods: Our study included DNA samples from two studies (NEIGHBOR and GLAUGEN). All the samples were genotyped with the Illumina Human660W_Quad_v1 BeadChip. After removing non–blood-derived and amplified DNA samples, we applied quality control steps based on the mean Log R Ratio and the mean B allele frequency. Subsequently, data from 3057 DNA samples (1599 cases and 1458 controls) were analyzed with PennCNV software. We defined CNVs as those ≥5 kilobases (kb) in size and interrogated by ≥5 consecutive probes. We further limited our investigation to CNVs in known POAG-related genes, including CDKN2B-AS1, TMCO1, SIX1/SIX6, CAV1/CAV2, the LRP12-ZFPM2 region, GAS7, ATOH7, FNDC3B, CYP1B1, MYOC, OPTN, WDR36, SRBD1, TBK1, and GALC.Results: Genomic duplications of CDKN2B-AS1 and TMCO1 were each found in a single case. Two cases carried duplications in the GAS7 region. Genomic deletions of SIX6 and ATOH7 were each identified in one case. One case carried a TBK1 deletion and another case carried a TBK1 duplication. No controls had duplications or deletions in these six genes. A single control had a duplication in the MYOC region. Deletions of GALC were observed in five cases and two controls.Conclusions: The CNV analysis of a large set of cases and controls revealed the presence of rare CNVs in known POAG susceptibility genes. Our data suggest that these rare CNVs may contribute to POAG pathogenesis and merit functional evaluation.

AB - Purpose: We examined the role of DNA copy number variants (CNVs) of known glaucoma genes in relation to primary open angle glaucoma (POAG).Methods: Our study included DNA samples from two studies (NEIGHBOR and GLAUGEN). All the samples were genotyped with the Illumina Human660W_Quad_v1 BeadChip. After removing non–blood-derived and amplified DNA samples, we applied quality control steps based on the mean Log R Ratio and the mean B allele frequency. Subsequently, data from 3057 DNA samples (1599 cases and 1458 controls) were analyzed with PennCNV software. We defined CNVs as those ≥5 kilobases (kb) in size and interrogated by ≥5 consecutive probes. We further limited our investigation to CNVs in known POAG-related genes, including CDKN2B-AS1, TMCO1, SIX1/SIX6, CAV1/CAV2, the LRP12-ZFPM2 region, GAS7, ATOH7, FNDC3B, CYP1B1, MYOC, OPTN, WDR36, SRBD1, TBK1, and GALC.Results: Genomic duplications of CDKN2B-AS1 and TMCO1 were each found in a single case. Two cases carried duplications in the GAS7 region. Genomic deletions of SIX6 and ATOH7 were each identified in one case. One case carried a TBK1 deletion and another case carried a TBK1 duplication. No controls had duplications or deletions in these six genes. A single control had a duplication in the MYOC region. Deletions of GALC were observed in five cases and two controls.Conclusions: The CNV analysis of a large set of cases and controls revealed the presence of rare CNVs in known POAG susceptibility genes. Our data suggest that these rare CNVs may contribute to POAG pathogenesis and merit functional evaluation.

KW - DNA copy number variants

KW - GAS7

KW - Genetics

KW - POAG

KW - SIX6

UR - http://www.scopus.com/inward/record.url?scp=84919329285&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84919329285&partnerID=8YFLogxK

U2 - 10.1167/iovs.14-15712

DO - 10.1167/iovs.14-15712

M3 - Article

C2 - 25414181

AN - SCOPUS:84919329285

SN - 0146-0404

VL - 55

SP - 8251

EP - 8258

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

IS - 12

ER -

DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this