Systematic Design and Comparison of Expanded Carrier Screening Panels
| Autor: | Gabriel A. Lazarin, James D. Goldberg, Kyle A. Beauchamp, Eric A. Evans, Sophie I. Candille, Imran S. Haque, Kenny K. Wong, K. Eerik Kaseniit, H. Peter Kang, Rebecca Mar-Heyming, Dale Muzzey, Nikita Mehta, Gregory J. Hogan, Kambiz Karimi |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Computer science expanded carrier screening Population Design elements and principles Classification scheme Computational biology 030105 genetics & heredity 03 medical and health sciences Humans Genetic Predisposition to Disease Genetic Testing Original Research Article education Mendelian disorders Genetics (clinical) Genetic Association Studies Genetics education.field_of_study High prevalence Guideline adherence Genetic Carrier Screening Genetic Diseases Inborn Reproducibility of Results Genomics 030104 developmental biology Risk analysis (engineering) Female next-generation sequencing Guideline Adherence Detection rate Carrier screening |
| Zdroj: | Genetics in Medicine |
| DOI: | 10.1101/080713 |
| Popis: | PurposeThe recent growth in pan-ethnic expanded carrier screening (ECS) has raised questions about how such panels might be designed and evaluated systematically. Design principles for ECS panels might improve clinical detection of at-risk couples and facilitate objective discussions of panel choice.MethodsGuided by medical-society statements, we propose a method for the design of ECS panels that aims to maximize the aggregate and per-disease sensitivity and specificity across a range of Mendelian disorders considered serious by a systematic classification scheme. We evaluated this method retrospectively using results from 474,644 de-identified carrier screens. We then constructed several idealized panels to highlight strengths and limitations of different ECS methodologies.ResultsBased on modeled fetal risks for “severe” and “profound” diseases, a commercially available ECS panel (Counsyl) is expected to detect 183 affected conceptuses per 100,000 US births. A screen’s sensitivity is greatly impacted by two factors: (1) the methodology used (e.g., full-exon sequencing finds more affected conceptuses than targeted genotyping), and (2) the detection rate of the screen for diseases with high prevalence and complex molecular genetics (e.g., fragile X syndrome).ConclusionThe described approaches allow principled, quantitative evaluation of which diseases and methodologies are appropriate for pan-ethnic expanded carrier screening. |
| Databáze: | OpenAIRE |
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