PUBLICATION

A hypomorphic variant in EYS detected by genome-wide association study contributes toward retinitis pigmentosa

Authors
Nishiguchi, K.M., Miya, F., Mori, Y., Fujita, K., Akiyama, M., Kamatani, T., Koyanagi, Y., Sato, K., Takigawa, T., Ueno, S., Tsugita, M., Kunikata, H., Cisarova, K., Nishino, J., Murakami, A., Abe, T., Momozawa, Y., Terasaki, H., Wada, Y., Sonoda, K.H., Rivolta, C., Tsunoda, T., Tsujikawa, M., Ikeda, Y., Nakazawa, T.
ID
ZDB-PUB-210131-6
Date
2021
Source
Communications biology   4: 140 (Journal)
Registered Authors
Tsujikawa, Motokazu
Keywords
none
MeSH Terms
  • High-Throughput Nucleotide Sequencing
  • Polymorphism, Single Nucleotide*
  • Eye Proteins/genetics*
  • Eye Proteins/metabolism
  • Genome-Wide Association Study
  • Japan
  • Risk Factors
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Cell Line
  • Genetic Predisposition to Disease
  • Linkage Disequilibrium
  • Case-Control Studies
  • Animals
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Phenotype
  • Retinitis Pigmentosa/diagnosis
  • Retinitis Pigmentosa/ethnology
  • Retinitis Pigmentosa/genetics*
  • Retinitis Pigmentosa/metabolism
  • Mutation*
  • Asian People/genetics
  • Humans
  • Risk Assessment
(all 25)
PubMed
33514863 Full text @ Commun Biol
Abstract
The genetic basis of Japanese autosomal recessive retinitis pigmentosa (ARRP) remains largely unknown. Herein, we applied a 2-step genome-wide association study (GWAS) in 640 Japanese patients. Meta-GWAS identified three independent peaks at P < 5.0 × 10-8, all within the major ARRP gene EYS. Two of the three were each in linkage disequilibrium with a different low frequency variant (allele frequency < 0.05); a known founder Mendelian mutation (c.4957dupA, p.S1653Kfs*2) and a non-synonymous variant (c.2528 G > A, p.G843E) of unknown significance. mRNA harboring c.2528 G > A failed to restore rhodopsin mislocalization induced by morpholino-mediated knockdown of eys in zebrafish, consistent with the variant being pathogenic. c.2528 G > A solved an additional 7.0% of Japanese ARRP cases. The third peak was in linkage disequilibrium with a common non-synonymous variant (c.7666 A > T, p.S2556C), possibly representing an unreported disease-susceptibility signal. GWAS successfully unraveled genetic causes of a rare monogenic disorder and identified a high frequency variant potentially linked to development of local genome therapeutics.
Genes / Markers
Figures
Figure Gallery (4 images)
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Expression
Phenotype
Mutations / Transgenics
No data available
Human Disease / Model
Sequence Targeting Reagents
Target Reagent Reagent Type
eysMO1-eysMRPHLNO
eysMO2-eysMRPHLNO
eysMO3-eysMRPHLNO
eysMO4-eysMRPHLNO
1 - 4 of 4
Show
Fish
Antibodies
Name Type Antigen Genes Isotypes Host Organism
Ab1-eyspolyclonalIgGRabbit
Ab6-rhopolyclonal
    IgGRabbit
    1 - 2 of 2
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    Orthology
    Gene Orthology
    eys
    1 - 1 of 1
    Show
    Engineered Foreign Genes
    No data available
    Mapping
    No data available