Uploaded August 2025 | Updated September 2026, 3 hours ago
What if the key to understanding a genetic condition lies within a gene that standard tools often struggle to analyze? For hundreds of medically important genes like SMN1 and CYP21A2, highly similar paralogs and pseudogenes create genomic blind spots, making variant calling challenging. In this installment of the Spotlight on Human Genomics series, PacBio bioinformatics scientist Xiao Chen introduces Paraphase, a tool designed to resolve these complex regions.
Discover how Paraphase leverages HiFi long-read sequencing to address ambiguous read alignments. By realigning all reads from a gene and its paralogs to a single locus, the tool phases them into distinct, full-length haplotypes. This approach supports copy number determination, phased small variant calling, and the characterization of complex events like gene conversions and large deletions.
See real-world examples where Paraphase helps resolve the complete sequences of SMN1 and SMN2 to help identify silent carriers for spinal muscular atrophy in research, untangles complex biallelic variants in CYP21A2 for congenital adrenal hyperplasia research, and detects de novo gene conversions in trio studies.
00:00 The challenge of paralogous genes
01:14 Introducing Paraphase: a new approach
02:47 Resolving SMN1 and SMN2 with HiFi data
04:44 Scope of Paraphase: 316 medically important genes
05:23 Understanding Paraphase inputs and outputs
06:53 Application 1: Finding silent carriers of SMA
07:43 Application 2: Solving complex CYP21A2 cases
09:16 Application 3: Detecting de novo gene conversions
Subscribe for more insights from PacBio: youtube.com/@PacificBiosciences?sub_confirmation=1
Learn more about PacBio at pacb.com
Legal & Trademarks: Visit pacb.com/legal-and-trademarks
What if the key to understanding a genetic condition lies within a gene that standard tools often struggle to analyze? For hundreds of medically important genes like SMN1 and CYP21A2, highly similar paralogs and pseudogenes create genomic blind spots, making variant calling challenging. In this installment of the Spotlight on Human Genomics series, PacBio bioinformatics scientist Xiao Chen introduces Paraphase, a tool designed to resolve these complex regions.
Discover how Paraphase leverages HiFi long-read sequencing to address ambiguous read alignments. By realigning all reads from a gene and its paralogs to a single locus, the tool phases them into distinct, full-length haplotypes. This approach supports copy number determination, phased small variant calling, and the characterization of complex events like gene conversions and large deletions.
See real-world examples where Paraphase helps resolve the complete sequences of SMN1 and SMN2 to help identify silent carriers for spinal muscular atrophy in research, untangles complex biallelic variants in CYP21A2 for congenital adrenal hyperplasia research, and detects de novo gene conversions in trio studies.
00:00 The challenge of paralogous genes
01:14 Introducing Paraphase: a new approach
02:47 Resolving SMN1 and SMN2 with HiFi data
04:44 Scope of Paraphase: 316 medically important genes
05:23 Understanding Paraphase inputs and outputs
06:53 Application 1: Finding silent carriers of SMA
07:43 Application 2: Solving complex CYP21A2 cases
09:16 Application 3: Detecting de novo gene conversions
Subscribe for more insights from PacBio: youtube.com/@PacificBiosciences?sub_confirmation=1
Learn more about PacBio at pacb.com
Legal & Trademarks: Visit pacb.com/legal-and-trademarks
