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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)8251-8258
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume55
Issue number12
DOIs
StatePublished - Nov 20 2014

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DNA Copy Number Variations
Glaucoma
Genes
DNA
Gene Frequency
Quality Control
Software
Primary Open Angle Glaucoma

Keywords

  • DNA copy number variants
  • GAS7
  • Genetics
  • POAG
  • SIX6

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Liu, Y., Garrett, M. E., Yaspan, B. L., Bailey, J. C., Loomis, S. J., Brilliant, M., ... 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

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

In: Investigative Ophthalmology and Visual Science, Vol. 55, No. 12, 20.11.2014, p. 8251-8258.

Research output: Contribution to journalArticle

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
Liu, Yutao ; Garrett, Melanie E. ; Yaspan, Brian L. ; Bailey, Jessica Cooke ; Loomis, Stephanie J. ; Brilliant, Murray ; Budenz, Donald L. ; Christen, William G. ; Fingert, John H. ; Gaasterland, Douglas ; Gaasterland, Terry ; Kang, Jae H. ; Lee, Richard K. ; Lichter, Paul ; Moroi, Sayoko E. ; Realini, Anthony ; Richards, Julia E. ; Schuman, Joel S. ; Scott, William K. ; Singh, Kuldev ; Sit, Arthur J. ; Vollrath, Douglas ; Weinreb, Robert ; Wollstein, Gadi ; Zack, Donald J. ; Zhang, Kang ; Pericak-Vance, Margaret A. ; Haines, Jonathan L. ; Pasquale, Louis R. ; Wiggs, Janey L. ; Allingham, R. Rand ; Ashley-Koch, Allison E. ; Hauser, Michael A. / DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma. In: Investigative Ophthalmology and Visual Science. 2014 ; Vol. 55, No. 12. pp. 8251-8258.
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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.}",
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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

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