{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T23:55:09Z","timestamp":1768348509545,"version":"3.49.0"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T00:00:00Z","timestamp":1567468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["18-415-130008"],"award-info":[{"award-number":["18-415-130008"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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\u2010scale projects, such as the Russian population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2010based autosomal recessive (AR) disease allele prevalence as compared to gnomAD r. 2.1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 (<jats:italic>ATP7B<\/jats:italic>, rs76151636), factor VII deficiency (<jats:italic>F7<\/jats:italic>, rs36209567), kyphoscoliosis type of Ehlers\u2010Danlos syndrome (<jats:italic>FKBP14<\/jats:italic>, 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our observations demonstrate the utility of population\u2010specific allele frequency data to the diagnosis of monogenic disorders using high\u2010throughput technologies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.964","type":"journal-article","created":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T01:44:41Z","timestamp":1567561481000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Whole\u2010exome sequencing provides insights into monogenic disease prevalence in Northwest Russia"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3222-440X","authenticated-orcid":false,"given":"Yury A.","family":"Barbitoff","sequence":"first","affiliation":[{"name":"Bioinformatics Institute St. Petersburg Russia"},{"name":"Department of Genetics and Biotechnology St. Petersburg State University St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rostislav K.","family":"Skitchenko","sequence":"additional","affiliation":[{"name":"Bioinformatics Institute St. Petersburg Russia"},{"name":"ITMO University St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga I.","family":"Poleshchuk","sequence":"additional","affiliation":[{"name":"Bioinformatics Institute St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7084-0177","authenticated-orcid":false,"given":"Anton E.","family":"Shikov","sequence":"additional","affiliation":[{"name":"Bioinformatics Institute St. Petersburg Russia"},{"name":"City Hospital No. 40 St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena A.","family":"Serebryakova","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine D.O. Ott Research Institute of Obstetrics, Gynaecology and Reproduction St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia A.","family":"Nasykhova","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine D.O. Ott Research Institute of Obstetrics, Gynaecology and Reproduction St. Petersburg Russia"},{"name":"Laboratory of Biobanking and Genomic Medicine of Institute of Translation Biomedicine St. Petersburg State University St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9679-2791","authenticated-orcid":false,"given":"Dmitrii E.","family":"Polev","sequence":"additional","affiliation":[{"name":"Cerbalab LTD St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna R.","family":"Shuvalova","sequence":"additional","affiliation":[{"name":"Cerbalab LTD St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina V.","family":"Shcherbakova","sequence":"additional","affiliation":[{"name":"Laboratory of Biobanking and Genomic Medicine of Institute of Translation Biomedicine St. Petersburg State University St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail A.","family":"Fedyakov","sequence":"additional","affiliation":[{"name":"City Hospital No. 40 St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleg S.","family":"Glotov","sequence":"additional","affiliation":[{"name":"City Hospital No. 40 St. Petersburg Russia"},{"name":"Department of Genomic Medicine D.O. 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Ott Research Institute of Obstetrics, Gynaecology and Reproduction St. Petersburg Russia"},{"name":"Laboratory of Biobanking and Genomic Medicine of Institute of Translation Biomedicine St. Petersburg State University St. Petersburg Russia"},{"name":"Institute of Living Systems Immanuel Kant Baltic Federal University Kaliningrad Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2750-1599","authenticated-orcid":false,"given":"Alexander V.","family":"Predeus","sequence":"additional","affiliation":[{"name":"Bioinformatics Institute St. Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,9,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.24075\/brsmu.2016-06-04"},{"key":"e_1_2_8_3_1","first-page":"32","article-title":"High carrier frequency of CFTR gene mutations associated with cystic fibrosis, and PAH gene mutations associated with phenylketonuria in Russian population","volume":"4","author":"Abramov D. 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