Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
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
_version_ 1783464968783396864
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
work_keys_str_mv AT barbitoffyurya wholeexomesequencingprovidesinsightsintomonogenicdiseaseprevalenceinnorthwestrussia
AT skitchenkorostislavk wholeexomesequencingprovidesinsightsintomonogenicdiseaseprevalenceinnorthwestrussia
AT poleshchukolgai wholeexomesequencingprovidesinsightsintomonogenicdiseaseprevalenceinnorthwestrussia
AT shikovantone wholeexomesequencingprovidesinsightsintomonogenicdiseaseprevalenceinnorthwestrussia
AT serebryakovaelenaa wholeexomesequencingprovidesinsightsintomonogenicdiseaseprevalenceinnorthwestrussia
AT nasykhovayuliaa wholeexomesequencingprovidesinsightsintomonogenicdiseaseprevalenceinnorthwestrussia
AT polevdmitriie wholeexomesequencingprovidesinsightsintomonogenicdiseaseprevalenceinnorthwestrussia
AT shuvalovaannar wholeexomesequencingprovidesinsightsintomonogenicdiseaseprevalenceinnorthwestrussia
AT shcherbakovairinav wholeexomesequencingprovidesinsightsintomonogenicdiseaseprevalenceinnorthwestrussia
AT fedyakovmikhaila wholeexomesequencingprovidesinsightsintomonogenicdiseaseprevalenceinnorthwestrussia
AT glotovolegs wholeexomesequencingprovidesinsightsintomonogenicdiseaseprevalenceinnorthwestrussia
AT glotovandreys wholeexomesequencingprovidesinsightsintomonogenicdiseaseprevalenceinnorthwestrussia
AT predeusalexanderv wholeexomesequencingprovidesinsightsintomonogenicdiseaseprevalenceinnorthwestrussia