September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Linkage Analysis of Common Myopia using Whole Exome Genotyping in Highly Aggregated Ashkenazi Families Replicates Loci on Chromosomes 1 and 7.
Author Affiliations & Notes
  • Claire L Simpson
    Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland, United States
    Genetics, Genomics and Informatics, University of Tennessee Health Sciences Center, Memphis, Tennessee, United States
  • Anthony M Musolf
    Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland, United States
  • Laura Portas
    Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland, United States
  • Federico Murgia
    Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland, United States
  • Qing Li
    Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland, United States
  • Joan E Bailey-Wilson
    Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland, United States
  • Dwight Stambolian
    Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Claire Simpson, None; Anthony Musolf, None; Laura Portas, None; Federico Murgia, None; Qing Li, None; Joan Bailey-Wilson, None; Dwight Stambolian, None
  • Footnotes
    Support  5-R01-EY-020483-05
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4839. doi:
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      Claire L Simpson, Anthony M Musolf, Laura Portas, Federico Murgia, Qing Li, Joan E Bailey-Wilson, Dwight Stambolian; Linkage Analysis of Common Myopia using Whole Exome Genotyping in Highly Aggregated Ashkenazi Families Replicates Loci on Chromosomes 1 and 7.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4839.

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

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Abstract

Purpose : To perform linkage analyses on highly aggregated Ashkenazi Jewish families with common myopia.

Methods : Sixty-four extended Ashkenazi Jewish families previously collected from New Jersey. Genotypes from Illumina Exome Array merged with microsatellite linkage panel from prior analyses of these families. Additional markers added as custom array content for candidate regions reported in literature for myopia or refractive error. Myopia defined as mean spherical equivalent (MSE) of -1D or worse and both parametric two-point linkage analyses (using MCLink) and multi-point linkage analyses (using SimWalk2) were performed.

Results : The strongest overall evidence of linkage was on 1p36, with a maximum two-point LOD score of 4.53. This location was a candidate region (MYP14) previously linked to MSE but not myopia. The second strongest linkage peak was on 7p15, with a maximum two-point LOD score of 4.35. This location has not previously been linked to myopia or MSE in these families but has been previously reported in our cohort of African Americans (MYP17). When Examiningof individual family LOD scores, strongest evidence of linkage was on 6q in Family 1019, where 13 variants had LOD scores between 2.71 - 2.96. This region contains several interesting candidate genes including AKAP12, a cell growth related kinaseThis family also had a promising signal on chromosome 4, with 21 variants ranging from 1.8 – 1.99. Family 1023 displayed a strong signal on chromosome 10 (11 variants ranging from 2.3 – 2.5) with interesting candidate genes in cell adhesion (CTNNA), scaffolding (DLG5), and cellular differentiation (DUSP13). The last strong linkage peak was from Family 1068 on chromosome 3p. There were 13 variants in the region ranging in LOD score from 1.8 – 2.02. One of the more interesting candidate genes in this region is PDZRN3, which is involved in cellular differentiation and is known to be expressed in the retina.

Conclusions : We have replicated 2 loci, one previously reported in refractive error but not myopia in these families and the other locus previously reported in our African American myopia families. We also identified 4 interesting linkage peaks for myopia on chromosomes 3, 4, 6, and 10 in these Ashkenazi Jewish families. Targeted sequencing in these regions to will be necessary to further find causal variants under these linkage peaks.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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