Identification of recurrent pathogenic alleles using exome sequencing data: Proof-of-concept study of Russian subjects |
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| Affiliation: | 1. St.-Petersburg State Pediatric Medical University, St.-Petersburg, 194100, Russia;2. N.N. Petrov Institute of Oncology, St.-Petersburg, 197758, Russia;3. I.I. Mechnikov North-Western Medical University, St.-Petersburg, 191015, Russia;1. Dept. Pediatrics, University of California San Francisco, San Francisco, CA, 94143, USA;2. UFR Des Sciences de Santé, INSERM-Université de Bourgogne UMR1231, Génétique des Anomalies du Développement, Dijon, France;3. Department of Pathology, CHU Rouen, F-76000, Rouen, France;4. Department of Obstetrics, Gynecology, & Reproductive Sciences, University of California San Francisco, San Francisco, CA, 94143, USA;5. Dept. Cytogenetics, University of California San Francisco, San Francisco, CA, 94143, USA;6. Dept. Pathology, University of California San Francisco, San Francisco, CA, 94143, USA;1. Service de Génétique, Laboratoire de Cytogénétique Constitutionnelle, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Bron, France;2. Lyon Neuroscience Research Center, GENDEV Team, CNRS UMR 5292, INSERM U1028, UCBL1, Bron, France;3. Université Claude Bernard Lyon 1, France;4. Service de Génétique, Hôpital de la Timone Enfant, APHM, Marseille, France;5. Division of Metabolics, Children''s Hospital of Eastern Ontario, Ottawa, Ontario, Canada;6. Centre Hospitalier de Valence, Service de pédiatrie, Valence, France;1. Genetics Division, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil;2. Medicine Department, Marília University (UNIMAR), Marília, São Paulo, Brazil;3. Division of Child Neurology, Reference Center for Neuromuscular Diseases, Department of Pediatrics, CHR, University of Liège, Belgium;1. National Research Institute for Family Planning, Beijing, China;2. National Human Genetic Resources Center, Beijing, China;3. Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China;4. Department of Otolaryngology, PLA General Hospital, Beijing, China;5. School of Life Science and Technology, ShanghaiTech University, Shanghai, China;1. CHU Grenoble Alpes, Genetic Service, Department of Genetics and Procreation, Grenoble, France;2. CHU Saint Etienne, Genetic Service, Hôpital de Nord, Saint Etienne, France;3. Centre Léon Bérard, Laboratory of Constitutional Genetics for Frequent Cancers HCL-CLB, Lyon, France;4. Centre Léon Bérard, Department of Medicine, Lyon, France;5. Centre Léon Bérard, Cancer Genetics Unit, Department of Public Health, Lyon, France;6. Hôpital Arnaud de Villeneuve, Cellular and Hormonal Biology Service, Montpellier, France;7. CHU Dijon Bourgogne, Genetic and Rare Disease Reference Center for Development Abnormalities in the East Interregion, Children''s Hospital, Dijon, France;8. Centre Georges François Leclerc, Department of Pathology and Tumor Biology, Dijon, France;9. Hôpital Cochin, Genetic and Molecular Biology Service, Paris, France;1. University of Toronto, Toronto, Ontario, Canada;2. The Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael''s Hospital, Toronto, Ontario, Canada;3. Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada;4. McMaster University, Hamilton, Ontario, Canada;5. Sunnybrook Hospital, Toronto, Ontario, Canada;6. Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada;7. University Health Network, Toronto, Ontario, Canada |
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| Abstract: | Whole exome sequencing (WES) is a powerful tool for the cataloguing of population-specific genetic diseases. Within this proof-of-concept study we evaluated whether analysis of a small number of individual exomes is capable of identifying recurrent pathogenic alleles. We considered 106 exomes of subjects of Russian origin and revealed 13 genetic variants, which occurred more than twice and fulfilled the criteria for pathogenicity. All these alleles turned out to be indeed recurrent, as revealed by the analysis of 1045 healthy Russian donors. Eight of these variants (NAGA c.973G>A, ACADM c.985A>C, MPO c.2031-2A>C, SLC3A1 c.1400T>C, LRP2 c.6160G>A, BCHE c.293A>G, MPO c.752T>C, FCN3 c.349delC) are non-Russian-specific, as their high prevalence was previously demonstrated in other European populations. The remaining five disease-associated alleles appear to be characteristic for subjects of Russian origin and include CLCN1 c.2680C>T (myotonia congenita), DHCR7 c.453G>A (Smith-Lemli-Opitz syndrome), NUP93 c.1162C>T (steroid-resistant nephrotic syndrome, type 12), SLC26A2 c.1957T>A (multiple epiphyseal dysplasia) and EIF3F c.694T>G (mental retardation). These recessive disease conditions may be of particular relevance for the Russian Federation and other countries with a significant Slavic population. |
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| Keywords: | Germ-line variants Recessive genetic conditions Founder effect Whole exome sequencing |
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