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...
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ftdoajarticles:oai:doaj.org/article:8047bdd641c54668bc1ab8afc74830ac 2024-09-15T18:26:28+00:00 Whole‐exome sequencing provides insights into monogenic disease prevalence in Northwest Russia 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 2019-11-01T00:00:00Z https://doi.org/10.1002/mgg3.964 https://doaj.org/article/8047bdd641c54668bc1ab8afc74830ac EN eng Wiley https://doi.org/10.1002/mgg3.964 https://doaj.org/toc/2324-9269 2324-9269 doi:10.1002/mgg3.964 https://doaj.org/article/8047bdd641c54668bc1ab8afc74830ac Molecular Genetics & Genomic Medicine, Vol 7, Iss 11, Pp n/a-n/a (2019) allele frequency Mendelian disease Russia whole‐exome sequencing Genetics QH426-470 article 2019 ftdoajarticles https://doi.org/10.1002/mgg3.964 2024-08-05T17:49:57Z 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 Directory of Open Access Journals: DOAJ Articles Molecular Genetics & Genomic Medicine 7 11 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
allele frequency Mendelian disease Russia whole‐exome sequencing Genetics QH426-470 |
spellingShingle |
allele frequency Mendelian disease Russia whole‐exome sequencing Genetics QH426-470 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 |
topic_facet |
allele frequency Mendelian disease Russia whole‐exome sequencing Genetics QH426-470 |
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. |
format |
Article in Journal/Newspaper |
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 |
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 |
https://doi.org/10.1002/mgg3.964 https://doaj.org/article/8047bdd641c54668bc1ab8afc74830ac |
genre |
Northwest Russia |
genre_facet |
Northwest Russia |
op_source |
Molecular Genetics & Genomic Medicine, Vol 7, Iss 11, Pp n/a-n/a (2019) |
op_relation |
https://doi.org/10.1002/mgg3.964 https://doaj.org/toc/2324-9269 2324-9269 doi:10.1002/mgg3.964 https://doaj.org/article/8047bdd641c54668bc1ab8afc74830ac |
op_doi |
https://doi.org/10.1002/mgg3.964 |
container_title |
Molecular Genetics & Genomic Medicine |
container_volume |
7 |
container_issue |
11 |
_version_ |
1810466949429198848 |