May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Linkage and mutation analysis to identify the gene associated with macular degeneration segregating in a cynomolgus monkey (Macaca fascicularis) pedigree.
S. Umeda; R. Ayyagari; R. Allikmets; H. Okamoto; M.T. Suzuki; K. Terao; A. Mizota; Y. Yoshikawa; Y. Tanaka; T. Iwata
Author Affiliations & Notes
  • S. Umeda
    National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan
    Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
  • R. Ayyagari
    Department of Ophthalmology, Kellogg Eye Center, University of Michigan, Ann Arbor, MI
  • R. Allikmets
    Columbia University, New York, NY
  • H. Okamoto
    National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan
  • M.T. Suzuki
    The Corporation for Production and Research of Laboratory Primates, Tsukuba, Japan
  • K. Terao
    Tsukuba Primate Center for Medical Science, National Institute of Infectious Diseases, Tsukuba, Japan
  • A. Mizota
    Department of Ocular Oncology, Chiba University Graduate School of Medicine, Chiba, Japan
  • Y. Yoshikawa
    Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
  • Y. Tanaka
    National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan
  • T. Iwata
    National Institute of Sensory Organs, National Tokyo Medical Center, Tokyo, Japan
  • Footnotes
    Commercial Relationships  S. Umeda, None; R. Ayyagari, None; R. Allikmets, None; H. Okamoto, None; M.T. Suzuki, None; K. Terao, None; A. Mizota, None; Y. Yoshikawa, None; Y. Tanaka, None; T. Iwata, None.
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 1825. doi:
  • Views
  • Share
  • Tools
    • Alerts
      User Alerts
      You are adding an alert for:
      Linkage and mutation analysis to identify the gene associated with macular degeneration segregating in a cynomolgus monkey (Macaca fascicularis) pedigree.
      You will receive an email whenever this article is corrected, updated, or cited in the literature. You can manage this and all other alerts in My Account
      The alert will be sent to:
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation
      Citation

      S. Umeda, R. Ayyagari, R. Allikmets, H. Okamoto, M.T. Suzuki, K. Terao, A. Mizota, Y. Yoshikawa, Y. Tanaka, T. Iwata; Linkage and mutation analysis to identify the gene associated with macular degeneration segregating in a cynomolgus monkey (Macaca fascicularis) pedigree. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1825.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

      ×
    • Get Permissions
  • Supplements
Abstract

Abstract: : Purpose: To identify the gene associated with early onset autosomal dominant macular degeneration in a large monkey pedigree, which manifests grayish or yellowish white dots in the macula and lipofuscin deposit in the retinal pigment epithelium, using candidate gene approach and linkage analysis. Methods: We cloned the monkey homologues of ABCA4, VMD2, TIMP3, EFEMP1, and ELOVL4 as candidates. Mutation analysis was performed by PCR amplification of exons using DNA from 6 affected and 11 normal monkeys, followed by single strand confirmation polymorphism analysis and direct sequencing. Microsatellite markers linked to human macular degeneration loci were amplified using DNA from 20 affected monkeys and 6 unaffected relatives. Linkage analysis was carried out using MLINK program and affecteds–only model. Results: No pathogenic sequence change was identified in monkey genes homologous to the human VMD2, TIMP3, EFEMP1, and ELOVL4 gene. Sequences of these four monkey genes showed significant homology with their human counterparts. In addition, no significant positive LOD scores were obtained when tested for linkage with STGD1, STGD3, STGD4, ARMD1, DHRD, Sorsby’s fundus dystrophy, VMD2, MCDR1, CORD5, CORD8, and CORD9 loci. Conclusions: Involvement of VMD2, TIMP3, EFEMP1, and ELOVL4 loci has been excluded in the monkey pedigree by linkage, haplotype and mutation analysis. Furthermore, by linkage analysis, we have also excluded the loci for STGD1, STGD4, ARMD1, MCDR1, CORD5, CORD8 and CORD9 conditions showing phenotypic overlap with the disease observed in affected monkeys. Macular degeneration in our monkey pedigree is likely to be due to mutations in a novel gene. Cloning the gene involved in causing macular degeneration in these monkeys will provide a valuable model to study the mechanism of macular degeneration.

Keywords: age–related macular degeneration • linkage analysis • mutations 
© 2004, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×
This site uses cookies. By continuing to use our website, you are agreeing to our privacy policy.Accept