Research output: Contribution to journal › Article › peer-review
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 journal › Article › peer-review
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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