Identifying rare, medically relevant variation via population-based genomic screening in Alabama: opportunities and pitfalls.
Genet Med
; 23(2): 280-288, 2021 02.
Article
in En
| MEDLINE
| ID: mdl-32989269
ABSTRACT
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.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Genetic Testing
/
Genomics
Type of study:
Diagnostic_studies
/
Screening_studies
Limits:
Humans
Country/Region as subject:
America do norte
Language:
En
Journal:
Genet Med
Journal subject:
GENETICA MEDICA
Year:
2021
Type:
Article
Affiliation country:
United States