Estimating the age of the p.Cys433Arg variant in the MYOC gene in patients with primary open-angle glaucoma

Ana Maria Marques; Galina Ananina; Vital Paulino Costa; José Paulo Cabral de Vasconcellos; Mônica Barbosa de Melo

doi:10.1371/journal.pone.0207409

Estimating the age of the p.Cys433Arg variant in the MYOC gene in patients with primary open-angle glaucoma

PLoS One. 2018 Nov 16;13(11):e0207409. doi: 10.1371/journal.pone.0207409. eCollection 2018.

Authors

Ana Maria Marques¹, Galina Ananina¹, Vital Paulino Costa², José Paulo Cabral de Vasconcellos², Mônica Barbosa de Melo¹

Affiliations

¹ Center for Molecular Biology and Genetic Engineering (CBMEG), University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
² Department of Ophthalmology and Otorhinolaryngology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

Abstract

The aim of this study was to estimate the age of the Cys433Arg (c.1297T>C, p.Cys433Arg) variant by comparing the genotypes of individuals affected and not affected by primary open angle glaucoma juvenile onset (JOAG). Our sample consisted of 35 JOAG-affected individuals from three families, 16 unrelated patients with the MYOC p.Cys433Arg variant and 16 unaffected individuals. Genomic DNA was amplified by PCR; nine short tandem repeats were genotyped through automated electrophoresis and three single nucleotide polymorphisms through Sanger sequencing. The determination of haplotypes was performed using Arlequin software and age estimation was performed using DMLE+ 2.3 and BDMC21 softwares. Four markers constituted the haplotypes associated with the p.Cys433Arg variant. The software DMLE+2.3 predicted an age of 43 generations for this variant with a 95% confidence interval ranging from 28 to 76 generations (560-1520 years) and BDMC21 predicted an age of 59 generations (1180 years) (95% CI: 40 to 100).

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Amino Acid Substitution
Brazil / epidemiology
Cytoskeletal Proteins / genetics*
Eye Proteins / genetics*
Female
Genotype*
Glaucoma, Open-Angle / epidemiology
Glaucoma, Open-Angle / genetics*
Glycoproteins / genetics*
Humans
Male
Mutation, Missense*
Polymorphism, Single Nucleotide*

Substances

Cytoskeletal Proteins
Eye Proteins
Glycoproteins
trabecular meshwork-induced glucocorticoid response protein

Grants and funding

This work was supported by José Paulo Cabral de Vasconcellos (JPCV), São Paulo Research Foundation (FAPESP) grant 2002/11575-0, URL: http://www.fapesp.br/; Mônica Barbosa de Melo (MBM), São Paulo Research Foundation (FAPESP) grant 2010/18353-9, URL: http://www.fapesp.br/; Ana Maria Marques (AMM), Coordination for the Improvement of Higher Education Personnel (CAPES)-Program of Academic Excellence (PROEX) grant 0230081, URL: http://www.capes.gov.br/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.