Whole‐exome sequencing provides insights into monogenic disease prevalence in Northwest Russia
Abstract Background Allele frequency data from large exome and genome aggregation projects such as the Genome Aggregation Database (gnomAD) are of ultimate importance to the interpretation of medical resequencing data. However, allele frequencies might significantly differ in poorly studied populati...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-11-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.964 |
| _version_ | 1797296148188233728 |
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| author | Yury A. Barbitoff Rostislav K. Skitchenko Olga I. Poleshchuk Anton E. Shikov Elena A. Serebryakova Yulia A. Nasykhova Dmitrii E. Polev Anna R. Shuvalova Irina V. Shcherbakova Mikhail A. Fedyakov Oleg S. Glotov Andrey S. Glotov Alexander V. Predeus |
| author_facet | Yury A. Barbitoff Rostislav K. Skitchenko Olga I. Poleshchuk Anton E. Shikov Elena A. Serebryakova Yulia A. Nasykhova Dmitrii E. Polev Anna R. Shuvalova Irina V. Shcherbakova Mikhail A. Fedyakov Oleg S. Glotov Andrey S. Glotov Alexander V. Predeus |
| author_sort | Yury A. Barbitoff |
| collection | DOAJ |
| description | Abstract Background Allele frequency data from large exome and genome aggregation projects such as the Genome Aggregation Database (gnomAD) are of ultimate importance to the interpretation of medical resequencing data. However, allele frequencies might significantly differ in poorly studied populations that are underrepresented in large‐scale projects, such as the Russian population. Methods In this work, we leveraged our access to a large dataset of 694 exome samples to analyze genetic variation in the Northwest Russia. We compared the spectrum of genetic variants to the dbSNP build 151, and made estimates of ClinVar‐based autosomal recessive (AR) disease allele prevalence as compared to gnomAD r. 2.1. Results An estimated 9.3% of discovered variants were not present in dbSNP. We report statistically significant overrepresentation of pathogenic variants for several Mendelian disorders, including phenylketonuria (PAH, rs5030858), Wilson's disease (ATP7B, rs76151636), factor VII deficiency (F7, rs36209567), kyphoscoliosis type of Ehlers‐Danlos syndrome (FKBP14, rs542489955), and several other recessive pathologies. We also make primary estimates of monogenic disease incidence in the population, with retinal dystrophy, cystic fibrosis, and phenylketonuria being the most frequent AR pathologies. Conclusion Our observations demonstrate the utility of population‐specific allele frequency data to the diagnosis of monogenic disorders using high‐throughput technologies. |
| first_indexed | 2024-03-07T21:59:11Z |
| format | Article |
| id | doaj.art-8047bdd641c54668bc1ab8afc74830ac |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-03-07T21:59:11Z |
| publishDate | 2019-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-8047bdd641c54668bc1ab8afc74830ac2024-02-24T07:01:11ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-11-01711n/an/a10.1002/mgg3.964Whole‐exome sequencing provides insights into monogenic disease prevalence in Northwest RussiaYury A. Barbitoff0Rostislav K. Skitchenko1Olga I. Poleshchuk2Anton E. Shikov3Elena A. Serebryakova4Yulia A. Nasykhova5Dmitrii E. Polev6Anna R. Shuvalova7Irina V. Shcherbakova8Mikhail A. Fedyakov9Oleg S. Glotov10Andrey S. Glotov11Alexander V. Predeus12Bioinformatics Institute St. Petersburg RussiaBioinformatics Institute St. Petersburg RussiaBioinformatics Institute St. Petersburg RussiaBioinformatics Institute St. Petersburg RussiaDepartment of Genomic Medicine D.O. Ott Research Institute of Obstetrics, Gynaecology and Reproduction St. Petersburg RussiaDepartment of Genomic Medicine D.O. Ott Research Institute of Obstetrics, Gynaecology and Reproduction St. Petersburg RussiaCerbalab LTD St. Petersburg RussiaCerbalab LTD St. Petersburg RussiaLaboratory of Biobanking and Genomic Medicine of Institute of Translation Biomedicine St. Petersburg State University St. Petersburg RussiaCity Hospital No. 40 St. Petersburg RussiaCity Hospital No. 40 St. Petersburg RussiaCity Hospital No. 40 St. Petersburg RussiaBioinformatics Institute St. Petersburg RussiaAbstract Background Allele frequency data from large exome and genome aggregation projects such as the Genome Aggregation Database (gnomAD) are of ultimate importance to the interpretation of medical resequencing data. However, allele frequencies might significantly differ in poorly studied populations that are underrepresented in large‐scale projects, such as the Russian population. Methods In this work, we leveraged our access to a large dataset of 694 exome samples to analyze genetic variation in the Northwest Russia. We compared the spectrum of genetic variants to the dbSNP build 151, and made estimates of ClinVar‐based autosomal recessive (AR) disease allele prevalence as compared to gnomAD r. 2.1. Results An estimated 9.3% of discovered variants were not present in dbSNP. We report statistically significant overrepresentation of pathogenic variants for several Mendelian disorders, including phenylketonuria (PAH, rs5030858), Wilson's disease (ATP7B, rs76151636), factor VII deficiency (F7, rs36209567), kyphoscoliosis type of Ehlers‐Danlos syndrome (FKBP14, rs542489955), and several other recessive pathologies. We also make primary estimates of monogenic disease incidence in the population, with retinal dystrophy, cystic fibrosis, and phenylketonuria being the most frequent AR pathologies. Conclusion Our observations demonstrate the utility of population‐specific allele frequency data to the diagnosis of monogenic disorders using high‐throughput technologies.https://doi.org/10.1002/mgg3.964allele frequencyMendelian diseaseRussiawhole‐exome sequencing |
| spellingShingle | Yury A. Barbitoff Rostislav K. Skitchenko Olga I. Poleshchuk Anton E. Shikov Elena A. Serebryakova Yulia A. Nasykhova Dmitrii E. Polev Anna R. Shuvalova Irina V. Shcherbakova Mikhail A. Fedyakov Oleg S. Glotov Andrey S. Glotov Alexander V. Predeus Whole‐exome sequencing provides insights into monogenic disease prevalence in Northwest Russia Molecular Genetics & Genomic Medicine allele frequency Mendelian disease Russia whole‐exome sequencing |
| title | Whole‐exome sequencing provides insights into monogenic disease prevalence in Northwest Russia |
| title_full | Whole‐exome sequencing provides insights into monogenic disease prevalence in Northwest Russia |
| title_fullStr | Whole‐exome sequencing provides insights into monogenic disease prevalence in Northwest Russia |
| title_full_unstemmed | Whole‐exome sequencing provides insights into monogenic disease prevalence in Northwest Russia |
| title_short | Whole‐exome sequencing provides insights into monogenic disease prevalence in Northwest Russia |
| title_sort | whole exome sequencing provides insights into monogenic disease prevalence in northwest russia |
| topic | allele frequency Mendelian disease Russia whole‐exome sequencing |
| url | https://doi.org/10.1002/mgg3.964 |
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