Estimation of the mutation age c.1621C>T p.(Gln541*) in the FYCO1 gene responsible for the development of autosomal recessive congenital cataract in the Yakut population

The main cause of congenital or juvenile cataract with autosomal recessive inheritance in Yakutia is the c.1621C>T p.(Gln541*) nonsense mutation in the exon 8 of the FYCO1 gene. Previous studies have shown that the c.1621C>T p.(Gln541*) mutation has spread to the territory of Yakutia as a result of the founder effect. The initial assessment of the average “age” of the mutation using the data of linkage disequilibrium for three STR markers: D3S3685, D3S3582 and D3S3561 showed a result of ~10.4 ± 2.6 generations (260 ± 65.0 years). In the present study, we used a different approach to determine the “age” of the c.1621C>T p.(Gln541*) mutation using the DMLE+ 2.3 software based on the analysis of 25 SNP markers. The calculated DMLE+ 2.3 “age” of the mutation, taking into account the 95% confidence interval, varies from 25 to 67 generations (from 625 to 1675 years). Comprehensive data show that the c.1621C>T p.(Gln541*) mutation could have occurred between the 4th and 18th centuries with the most likely time of expansion from 11th century.

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