Reconstruction of the founder haplotype with mutation c.1621C>T (p.Gln541*) in the FYCO1 gene causing of autosomal recessive cataract (CTRCT18) in the Sakha Republic (Yakutia)

Previously, by using whole exome sequencing (WES), the nonsense mutation c.1621C>T (p.Gln541*) in the FYCO1 gene was revealed as the main genetic cause of congenital autosomal recessive cataract causing of in the Sakha Republic. In this paper we present the results of the c.1621C>T (p.Gln541*) carrier frequency analysis in 424 adult individuals without of visual impairments from 7 populations of Eastern Siberia (Russians, Yakuts, Evenks, Evens, Dolgans, Yukaghirs, and Chukchi). The highest carrier frequency of mutation c.1621C>T (p.Gln541*) was found in Yakut population (7.9%), the lowest - in Evenks (1.7%) and Evens (2.0%), and c.1621C>T (p.Gln541*) was absent in Russians, Yukaghirs, Dolgans and Chukchi. The analysis of haplotypes obtained as a result of genotyping of 6 STR markers flanking the FYCO1 gene was carried out in 25 patients homozygous for mutation c.1621C>T (p.Gln541*) and in 114 patients without this mutation. Common haplotypes bearing c.1621C>T (p.Gln541*) indicate the role of founder effect in the spread of this mutation in Yakutia. The highest diversity of the c.1621C>T-haplotypes was revealed in ethno-territorial group of Central Yakuts inhabiting the Leno-Amginsky interfluve. The mutant haplotypes of the Vilyui and Northern Yakut groups are probably derived from the c.1621C>T-haplotypes found in the Central Yakuts. Our results suggest that the novel mutation c.1621C>T (p.Gln541*) in the FYCO1 gene causing of autosomal recessive cataract (CTRCT18) spread among Yakut isolate population in Eastern Siberia (Russia) as a result of founder effect about 260 ± 65 years ago (10.4 ± 2.6 generations) i.e. in the middle of the XVIII century.

врожденная аутосомно-рецессивная катаракта, CTRCT18, c.1621C>, T (p.Gln541*), ген FYCO1, якуты, популяционный изолят, эффект основателя, Восточная Сибирь, congenital autosomal recessive cataract, CTRCT18, c.1621C>, T (p.Gln541*), FYCO1, Yakuts, population isolate, founder effect, Eastern Siberia

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