Mobile element insertion detection in 89,874 clinical exomes
| Autor: | Kyle Retterer, Carlos Borroto, Erin Beaver, Jane Juusola, Lorne A. Clarke, Kevin Galens, Zhancheng Zhang, Shuxi Liu, Jennifer Heeley, Kevin J. Arvai, Rebecca I. Torene, Jagdeep S. Walia, Julie Scuffins, Danna Hull, Bethany Friedman, Hana Sroka, Sarah Neil |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
mobile elements rare disease Binomial test Computational biology 030105 genetics & heredity Brief Communication DNA sequencing 03 medical and health sciences Exome Sequencing medicine diagnostics Humans Exome Genetic Testing Genetics (clinical) Exome sequencing Genetic testing medicine.diagnostic_test business.industry Sequence Analysis DNA Confidence interval 030104 developmental biology Mobile genetic elements Mendelian disease business Founder effect |
| Zdroj: | Genetics in Medicine |
| ISSN: | 1530-0366 1098-3600 |
| Popis: | Purpose Exome sequencing (ES) is increasingly used for the diagnosis of rare genetic disease. However, some pathogenic sequence variants within the exome go undetected due to the technical difficulty of identifying them. Mobile element insertions (MEIs) are a known cause of genetic disease in humans but have been historically difficult to detect via ES and similar targeted sequencing methods. Methods We developed and applied a novel MEI detection method prospectively to samples received for clinical ES beginning in November 2017. Positive MEI findings were confirmed by an orthogonal method and reported back to the ordering provider. In this study, we examined 89,874 samples from 38,871 cases. Results Diagnostic MEIs were present in 0.03% (95% binomial test confidence interval: 0.02–0.06%) of all cases and account for 0.15% (95% binomial test confidence interval: 0.08–0.25%) of cases with a molecular diagnosis. One diagnostic MEI was a novel founder event. Most patients with pathogenic MEIs had prior genetic testing, three of whom had previous negative DNA sequencing analysis of the diagnostic gene. Conclusion MEI detection from ES is a valuable diagnostic tool, reveals molecular findings that may be undetected by other sequencing assays, and increases diagnostic yield by 0.15%. |
| Databáze: | OpenAIRE |
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