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Association mapping of the high-grade myopia MYP3 locus reveals novel candidates UHRF1BP1L, PTPRR, and PPFIA2.
- Source :
-
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2013 Mar 21; Vol. 54 (3), pp. 2076-86. Date of Electronic Publication: 2013 Mar 21. - Publication Year :
- 2013
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Abstract
- Purpose: Myopia, or nearsightedness, is a common ocular genetic disease for which over 20 candidate genomic loci have been identified. The high-grade myopia locus, MYP3, has been reported on chromosome 12q21-23 by four independent linkage studies.<br />Methods: We performed a genetic association study of the MYP3 locus in a family-based high-grade myopia cohort (n = 82) by genotyping 768 single-nucleotide polymorphisms (SNPs) within the linkage region. Qualitative testing for high-grade myopia (sphere ≤ -5 D affected, > -0.5 D unaffected) and quantitative testing on the average dioptric sphere were performed.<br />Results: Several genetic markers were nominally significantly associated with high-grade myopia in qualitative testing, including rs3803036, a missense mutation in PTPRR (P = 9.1 × 10(-4)) and rs4764971, an intronic SNP in UHRF1BP1L (P = 6.1 × 10(-4)). Quantitative testing determined statistically significant SNPs rs4764971, also found by qualitative testing (P = 3.1 × 10(-6)); rs7134216, in the 3' untranslated region (UTR) of DEPDC4 (P = 5.4 × 10(-7)); and rs17306116, an intronic SNP within PPFIA2 (P < 9 × 10(-4)). Independently conducted whole genome expression array analyses identified protein tyrosine phosphatase genes PTPRR and PPFIA2, which are in the same gene family, as differentially expressed in normal rapidly growing fetal relative to normal adult ocular tissue (confirmed by RT-qPCR).<br />Conclusions: In an independent high-grade myopia cohort, an intronic SNP in UHRF1BP1L, rs4764971, was validated for quantitative association, and SNPs within PTPRR (quantitative) and PPFIA2 (qualitative and quantitative) approached significance. Three genes identified by our association study and supported by ocular expression and/or replication, UHRF1BP1L, PTPRR, and PPFIA2, are novel candidates for myopic development within the MYP3 locus that should be further studied.
- Subjects :
- Aged
Aged, 80 and over
Chromosome Mapping
Female
Genetic Markers
Genetic Predisposition to Disease
Humans
Intracellular Signaling Peptides and Proteins
Male
Middle Aged
Polymorphism, Single Nucleotide
Adaptor Proteins, Signal Transducing genetics
Carrier Proteins genetics
Genetic Linkage
Membrane Proteins genetics
Myopia genetics
Receptor-Like Protein Tyrosine Phosphatases, Class 7 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-5783
- Volume :
- 54
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Investigative ophthalmology & visual science
- Publication Type :
- Academic Journal
- Accession number :
- 23422819
- Full Text :
- https://doi.org/10.1167/iovs.12-11102