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Whole‐exome sequencing provides insights into monogenic disease prevalence in Northwest Russia
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825859/ https://www.ncbi.nlm.nih.gov/pubmed/31482689 http://dx.doi.org/10.1002/mgg3.964 |
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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. |
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. |
collection | PubMed |
description | 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 | Online Article Text |
id | pubmed-6825859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68258592019-11-07 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. Mol Genet Genomic Med Original Articles 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. John Wiley and Sons Inc. 2019-09-03 /pmc/articles/PMC6825859/ /pubmed/31482689 http://dx.doi.org/10.1002/mgg3.964 Text en © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles 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 |
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 | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825859/ https://www.ncbi.nlm.nih.gov/pubmed/31482689 http://dx.doi.org/10.1002/mgg3.964 |
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