Details

Autor(en) / Beteiligte

• Bowling, Kevin M
• Thompson, Michelle L
• Gray, David E
• Lawlor, James M J
• Williams, Kelly
• East, Kelly M
• Kelley, Whitley V
• Moss, Irene P
• Absher, Devin M
• Partridge, E Christopher
• Hurst, Anna C E
• Edberg, Jeffrey C
• Barsh, Gregory S
• Korf, Bruce R
• Cooper, Gregory M

Titel

Identifying rare, medically relevant variation via population-based genomic screening in Alabama: opportunities and pitfalls

Ist Teil von

• Genetics in medicine, 2021-02, Vol.23 (2), p.280-288

Ort / Verlag

United States: Elsevier Limited

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• To evaluate the effectiveness and specificity of population-based genomic screening in Alabama. 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. 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. 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.