Identifying rare, medically relevant variation via population-based genomic screening in Alabama: opportunities and pitfalls
| Autor: | Kelly M. East, Whitley V. Kelley, James M.J. Lawlor, Kelly Williams, Irene P. Moss, Gregory S. Barsh, Michelle L. Thompson, Devin Absher, Jeffrey C. Edberg, Gregory M. Cooper, Kevin M. Bowling, E. Christopher Partridge, David E. Gray, Bruce R. Korf, Anna C.E. Hurst |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Genetics Disease gene Sanger sequencing education.field_of_study Population Population based 030105 genetics & heredity Biology Genomic screening 03 medical and health sciences symbols.namesake 030104 developmental biology False positive paradox symbols Allele education Return of results Genetics (clinical) |
| Zdroj: | Genetics in Medicine. 23:280-288 |
| ISSN: | 1098-3600 |
| Popis: | Purpose To evaluate the effectiveness and specificity of population-based genomic screening in Alabama. Methods The Alabama Genomic Health Initiative (AGHI) has enrolled and evaluated 5369 participants for the presence of pathogenic/likely pathogenic (P/LP) variants using the Illumina Global Screening Array (GSA), with validation of all P/LP variants via Sanger sequencing in a CLIA-certified laboratory before return of results. Results Among 131 variants identified by the GSA that were evaluated by Sanger sequencing, 67 (51%) were false positives (FP). For 39 of the 67 FP variants, a benign/likely benign variant was present at or near the targeted P/LP variant. Variants detected within African American individuals were significantly enriched for FPs, likely due to a higher rate of nontargeted alternative alleles close to array-targeted P/LP variants. Conclusion In AGHI, we have implemented an array-based process to screen for highly penetrant genetic variants in actionable disease genes. We demonstrate the need for clinical validation of array-identified variants in direct-to-consumer or population testing, especially for diverse populations. |
| Databáze: | OpenAIRE |
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