Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region.

Autor:	Ramensky VE; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia.; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia., Ershova AI; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia., Zaicenoka M; Moscow Institute of Physics and Technology, Dolgoprudny, Moscow, Russia., Kiseleva AV; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia., Zharikova AA; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia.; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia., Vyatkin YV; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia.; Novosibirsk State University, Novosibirsk, Russia., Sotnikova EA; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia., Efimova IA; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia., Divashuk MG; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia.; All-Russia Research Institute of Agricultural Biotechnology, Moscow, Russia., Kurilova OV; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia., Skirko OP; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia., Muromtseva GA; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia., Belova OA; Cardiology Dispensary, Ivanovo, Russia., Rachkova SA; Cardiology Dispensary, Ivanovo, Russia., Pokrovskaya MS; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia., Shalnova SA; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia., Meshkov AN; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia., Drapkina OM; National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2021 Oct 07; Vol. 12, pp. 709419. Date of Electronic Publication: 2021 Oct 07 (Print Publication: 2021).
DOI:	10.3389/fgene.2021.709419
Abstrakt:	We performed a targeted sequencing of 242 clinically important genes mostly associated with cardiovascular diseases in a representative population sample of 1,658 individuals from the Ivanovo region northeast of Moscow. Approximately 11% of 11,876 detected variants were not found in the Single Nucleotide Polymorphism Database (dbSNP) or reported earlier in the Russian population. Most novel variants were singletons and doubletons in our sample, and virtually no novel alleles presumably specific for the Russian population were able to reach the frequencies above 0.1-0.2%. The overwhelming majority (99.3%) of variants detected in this study in three or more copies were shared with other populations. We found two dominant and seven recessive known pathogenic variants with allele frequencies significantly increased compared to those in the gnomAD non-Finnish Europeans. Of the 242 targeted genes, 28 were in the list of 59 genes for which the American College of Medical Genetics and Genomics (ACMG) recommended the reporting of incidental findings. Based on the number of variants detected in the sequenced subset of ACMG59 genes, we approximated the prevalence of known pathogenic and novel or rare protein-truncating variants in the complete set of ACMG59 genes in the Ivanovo population at 1.4 and 2.8%, respectively. We analyzed the available clinical data and observed the incomplete penetrance of known pathogenic variants in the 28 ACMG59 genes: only 1 individual out of 12 with such variants had the phenotype most likely related to the variant. When known pathogenic and novel or rare protein-truncating variants were considered together, the overall rate of confirmed phenotypes was about 19%, with maximum in the subset of novel protein-truncating variants. We report three novel protein truncating variants in APOB and one in MYH7 observed in individuals with hypobetalipoproteinemia and hypertrophic cardiomyopathy, respectively. Our results provide a valuable reference for the clinical interpretation of gene sequencing in Russian and other populations. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Ramensky, Ershova, Zaicenoka, Kiseleva, Zharikova, Vyatkin, Sotnikova, Efimova, Divashuk, Kurilova, Skirko, Muromtseva, Belova, Rachkova, Pokrovskaya, Shalnova, Meshkov and Drapkina.)
Databáze:	MEDLINE
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