A blended genome and exome sequencing method captures genetic variation in an unbiased, high-quality, and cost-effective manner

Document Type

Article

Department

Brain and Mind Institute

Abstract

We deployed the Blended Genome Exome (BGE), a DNA library blending approach that generates low pass whole genome (1-4x mean depth) and deep whole exome (30-40x mean depth) data in a single sequencing run. This technology is cost-effective, empowers most genomic discoveries possible with deep whole genome sequencing, and provides an unbiased method to capture the diversity of common SNP variation across the globe. To evaluate this new technology at scale, we applied BGE to sequence >53,000 samples from the Populations Underrepresented in Mental Illness Associations Studies (PUMAS) Project, which included participants across African, African American, and Latin American populations. We evaluated the accuracy of BGE imputed genotypes against raw genotype calls from the Illumina Global Screening Array. All PUMAS cohorts had R2 concordance ≥95% among SNPs with MAF≥1%, and never fell below ≥90% R2 for SNPs with MAF

Publication (Name of Journal)

bioRxiv

DOI

https://doi.org/10.1101/2024.09.06.611689

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