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2023 ACMG Annual Clinical Genetics Meeting Digital ...
Complete Resolution of Genes with Highly Homologou ...
Complete Resolution of Genes with Highly Homologous Gene Family Members or Pseudogenes Using Long-read PacBio HiFi Sequencing
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This document discusses the use of PacBio HiFi long-read sequencing to resolve genes with highly homologous gene family members or pseudogenes. Short read sequencing can struggle with accurately analyzing these challenging regions due to high sequence homology and frequent copy number variants. The authors developed an informatics method called Paraphase1, which accurately genotypes highly homologous genes, and applied it to resolve ten clinically relevant genes.<br /><br />The document provides detailed results for three genomic regions, including PMS2 (Lynch syndrome), SMN1 (spinal muscular atrophy), and the RCCX module (C4A/B, CYP21A2, TNXB). For example, Paraphase resolved haplotypes of PMS2 and its pseudogene PMS2CL, showing gene conversion patterns. In the case of SMN1, Paraphase identified haplotypes and determined copy numbers, enabling the identification of standard carriers and calling pathogenic variants. <br /><br />The authors also highlight that Paraphase can be used for other clinically important genes, such as STRC, IKBKG, NCF1, NEB, F8, and CFC1, and is being extended to a generalized genome-wide caller for paralogs.<br /><br />Additionally, the document discusses the identification of copy number variants and pathogenic variants resulting from gene conversion in the RCCX module. It also analyzes the frequency of CNVs and pathogenic variants in CYP21A2 across different populations.<br /><br />Overall, Paraphase provides a comprehensive framework for resolving highly homologous genes and has the potential to improve the accuracy and understanding of these challenging genomic regions.
Asset Subtitle
Presenting Author - Xiao Chen, PhD; Co-Author - Michael A. Eberle, PhD;
Meta Tag
Bioinformatics
Genetic Testing
Genome sequencing
Genomic Methodologies
Genomic Structure
Population Genetics
Sequencing
Co-Author
Michael A. Eberle, PhD
Presenting Author
Xiao Chen, PhD
Keywords
PacBio HiFi
homologous genes
Paraphase1
clinically relevant genes
PMS2
SMN1
RCCX module
haplotypes
copy numbers
pathogenic variants
© 2024 American College of Medical Genetics and Genomics. All rights reserved.
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