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Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region. / Ramensky, Vasily E.; Ershova, Alexandra I.; Zaicenoka, Marija et al.

In: Frontiers in Genetics, Vol. 12, 709419, 07.10.2021.

Research output: Contribution to journalArticlepeer-review

Harvard

Ramensky, VE, Ershova, AI, Zaicenoka, M, Kiseleva, AV, Zharikova, AA, Vyatkin, YV, Sotnikova, EA, Efimova, IA, Divashuk, MG, Kurilova, OV, Skirko, OP, Muromtseva, GA, Belova, OA, Rachkova, SA, Pokrovskaya, MS, Shalnova, SA, Meshkov, AN & Drapkina, OM 2021, 'Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region', Frontiers in Genetics, vol. 12, 709419. https://doi.org/10.3389/fgene.2021.709419

APA

Ramensky, V. E., Ershova, A. I., Zaicenoka, M., Kiseleva, A. V., Zharikova, A. A., Vyatkin, Y. V., Sotnikova, E. A., Efimova, I. A., Divashuk, M. G., Kurilova, O. V., Skirko, O. P., Muromtseva, G. A., Belova, O. A., Rachkova, S. A., Pokrovskaya, M. S., Shalnova, S. A., Meshkov, A. N., & Drapkina, O. M. (2021). Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region. Frontiers in Genetics, 12, [709419]. https://doi.org/10.3389/fgene.2021.709419

Vancouver

Ramensky VE, Ershova AI, Zaicenoka M, Kiseleva AV, Zharikova AA, Vyatkin YV et al. Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region. Frontiers in Genetics. 2021 Oct 7;12:709419. doi: 10.3389/fgene.2021.709419

Author

Ramensky, Vasily E. ; Ershova, Alexandra I. ; Zaicenoka, Marija et al. / Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region. In: Frontiers in Genetics. 2021 ; Vol. 12.

BibTeX

@article{cc029f005e00403594b42ca106a056e3,
title = "Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region",
abstract = "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.",
keywords = "genetic testing, pathogenic variants, penetrance, rare variants, secondary findings",
author = "Ramensky, {Vasily E.} and Ershova, {Alexandra I.} and Marija Zaicenoka and Kiseleva, {Anna V.} and Zharikova, {Anastasia A.} and Vyatkin, {Yuri V.} and Sotnikova, {Evgeniia A.} and Efimova, {Irina A.} and Divashuk, {Mikhail G.} and Kurilova, {Olga V.} and Skirko, {Olga P.} and Muromtseva, {Galina A.} and Belova, {Olga A.} and Rachkova, {Svetlana A.} and Pokrovskaya, {Maria S.} and Shalnova, {Svetlana A.} and Meshkov, {Alexey N.} and Drapkina, {Oxana M.}",
note = "Funding Information: This study was supported by the State assignment no. 121021100127-8. VR acknowledges support by the RFBR and DFG joint research project no 20-54-12008. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Ramensky, Ershova, Zaicenoka, Kiseleva, Zharikova, Vyatkin, Sotnikova, Efimova, Divashuk, Kurilova, Skirko, Muromtseva, Belova, Rachkova, Pokrovskaya, Shalnova, Meshkov and Drapkina.",
year = "2021",
month = oct,
day = "7",
doi = "10.3389/fgene.2021.709419",
language = "English",
volume = "12",
journal = "Frontiers in Genetics",
issn = "1664-8021",
publisher = "Frontiers Media S.A.",

}

RIS

TY - JOUR

T1 - Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region

AU - Ramensky, Vasily E.

AU - Ershova, Alexandra I.

AU - Zaicenoka, Marija

AU - Kiseleva, Anna V.

AU - Zharikova, Anastasia A.

AU - Vyatkin, Yuri V.

AU - Sotnikova, Evgeniia A.

AU - Efimova, Irina A.

AU - Divashuk, Mikhail G.

AU - Kurilova, Olga V.

AU - Skirko, Olga P.

AU - Muromtseva, Galina A.

AU - Belova, Olga A.

AU - Rachkova, Svetlana A.

AU - Pokrovskaya, Maria S.

AU - Shalnova, Svetlana A.

AU - Meshkov, Alexey N.

AU - Drapkina, Oxana M.

N1 - Funding Information: This study was supported by the State assignment no. 121021100127-8. VR acknowledges support by the RFBR and DFG joint research project no 20-54-12008. Publisher Copyright: © Copyright © 2021 Ramensky, Ershova, Zaicenoka, Kiseleva, Zharikova, Vyatkin, Sotnikova, Efimova, Divashuk, Kurilova, Skirko, Muromtseva, Belova, Rachkova, Pokrovskaya, Shalnova, Meshkov and Drapkina.

PY - 2021/10/7

Y1 - 2021/10/7

N2 - 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.

AB - 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.

KW - genetic testing

KW - pathogenic variants

KW - penetrance

KW - rare variants

KW - secondary findings

UR - http://www.scopus.com/inward/record.url?scp=85117594046&partnerID=8YFLogxK

U2 - 10.3389/fgene.2021.709419

DO - 10.3389/fgene.2021.709419

M3 - Article

C2 - 34691145

AN - SCOPUS:85117594046

VL - 12

JO - Frontiers in Genetics

JF - Frontiers in Genetics

SN - 1664-8021

M1 - 709419

ER -

ID: 34563722