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...
Published in: | Molecular Genetics & Genomic Medicine |
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Online Access: | http://dx.doi.org/10.1002/mgg3.964 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fmgg3.964 https://onlinelibrary.wiley.com/doi/pdf/10.1002/mgg3.964 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/mgg3.964 |
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crwiley:10.1002/mgg3.964 2024-09-09T20:00:00+00:00 Whole‐exome sequencing provides insights into monogenic disease prevalence in Northwest Russia Barbitoff, Yury A. Skitchenko, Rostislav K. Poleshchuk, Olga I. Shikov, Anton E. Serebryakova, Elena A. Nasykhova, Yulia A. Polev, Dmitrii E. Shuvalova, Anna R. Shcherbakova, Irina V. Fedyakov, Mikhail A. Glotov, Oleg S. Glotov, Andrey S. Predeus, Alexander V. Russian Science Foundation 2019 http://dx.doi.org/10.1002/mgg3.964 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fmgg3.964 https://onlinelibrary.wiley.com/doi/pdf/10.1002/mgg3.964 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/mgg3.964 en eng Wiley http://creativecommons.org/licenses/by/4.0/ Molecular Genetics & Genomic Medicine volume 7, issue 11 ISSN 2324-9269 2324-9269 journal-article 2019 crwiley https://doi.org/10.1002/mgg3.964 2024-08-13T04:11:02Z 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. Article in Journal/Newspaper Northwest Russia Wiley Online Library Molecular Genetics & Genomic Medicine 7 11 |
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English |
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. |
author2 |
Russian Science Foundation |
format |
Article in Journal/Newspaper |
author |
Barbitoff, Yury A. Skitchenko, Rostislav K. Poleshchuk, Olga I. Shikov, Anton E. Serebryakova, Elena A. Nasykhova, Yulia A. Polev, Dmitrii E. Shuvalova, Anna R. Shcherbakova, Irina V. Fedyakov, Mikhail A. Glotov, Oleg S. Glotov, Andrey S. Predeus, Alexander V. |
spellingShingle |
Barbitoff, Yury A. Skitchenko, Rostislav K. Poleshchuk, Olga I. Shikov, Anton E. Serebryakova, Elena A. Nasykhova, Yulia A. Polev, Dmitrii E. Shuvalova, Anna R. Shcherbakova, Irina V. Fedyakov, Mikhail A. Glotov, Oleg S. Glotov, Andrey S. Predeus, Alexander V. Whole‐exome sequencing provides insights into monogenic disease prevalence in Northwest Russia |
author_facet |
Barbitoff, Yury A. Skitchenko, Rostislav K. Poleshchuk, Olga I. Shikov, Anton E. Serebryakova, Elena A. Nasykhova, Yulia A. Polev, Dmitrii E. Shuvalova, Anna R. Shcherbakova, Irina V. Fedyakov, Mikhail A. Glotov, Oleg S. Glotov, Andrey S. Predeus, Alexander V. |
author_sort |
Barbitoff, Yury A. |
title |
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_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_sort |
whole‐exome sequencing provides insights into monogenic disease prevalence in northwest russia |
publisher |
Wiley |
publishDate |
2019 |
url |
http://dx.doi.org/10.1002/mgg3.964 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fmgg3.964 https://onlinelibrary.wiley.com/doi/pdf/10.1002/mgg3.964 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/mgg3.964 |
genre |
Northwest Russia |
genre_facet |
Northwest Russia |
op_source |
Molecular Genetics & Genomic Medicine volume 7, issue 11 ISSN 2324-9269 2324-9269 |
op_rights |
http://creativecommons.org/licenses/by/4.0/ |
op_doi |
https://doi.org/10.1002/mgg3.964 |
container_title |
Molecular Genetics & Genomic Medicine |
container_volume |
7 |
container_issue |
11 |
_version_ |
1809931101620142080 |