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

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

Ana Maria Marques  1 , Galina Ananina  1 , Vital Paulino Costa  2 , José Paulo Cabral de Vasconcellos  2 , Mônica Barbosa de Melo  1
Affiliations
Clinical Trial

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

Ana Maria Marques et al. PLoS One. .

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).

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Map of Brazil emphasizing the Southeast region.
Southeast region of Brazil formed by the states of São Paulo (SP), Minas Gerais (MG), Rio de Janeiro (RJ) and Espírito Santo (ES). The red points represent the hometowns of the families (Botucatu, Tanabi and Mogi das Cruzes). Yellow points represent the hometowns of the unrelated patients (Campinas, Limeira, Americana, Mogi Guaçu, Jundiaí, Pirassununga, Itapira and Paraguaçu Paulista).
Fig 2
Fig 2. Representation of the haplotypes determined for individuals with the p.Cys433Arg variant at chromosome region 1q24.3.
Haplotypes are formed by the markers rs3219828 (STR), rs2266782 (SNP), rs2266780 (SNP) and rs2234708 (STR). Each number represents a different allele in each microsatellite marker, as the letters represent different alleles in each SNP. The rs74315338, highlighted in bold, corresponds to the variant of interest. The first column indicates the number of each haplotype constructed and corresponding proband identity for each haplotype (family and unrelated patients). The position of the MYOC gene in relation to the markers is represented.
Fig 3
Fig 3. Age estimation for the p.Cys433Arg variant as assessed by DMLE+2.3.
Histogram representing the age of the p.Cys433Arg variant in generations according to the probability of each age to occur, resulting from the iterations performed by the DMLE+ 2.3 software. Green bars indicate 95% CIs.
Fig 4
Fig 4. Age estimation for the p.Cys433Arg variant as assessed by BDMC21.
Distribution of likelihoods of the p.Cys433Arg variant age (in generations).
See this image and copyright information in PMC

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