{"title":"Advanced phasing techniques in congenital skin diseases","authors":"Ken Natsuga","doi":"10.1111/1346-8138.17597","DOIUrl":null,"url":null,"abstract":"<p>Phasing, the process of determining which alleles at different loci on homologous chromosomes belong together on the same chromosome, is crucial in the diagnosis and management of autosomal recessive diseases. Advances in long-read sequencing technologies have significantly enhanced our ability to accurately determine haplotypes. This review discusses the application of low-coverage long-read sequencing, nanopore Cas9-guided long-read sequencing, and adaptive sampling in phasing, highlighting their utility in complex clinical scenarios. Through clinical vignettes, we explore the importance of phasing in gene therapy design for recessive dystrophic epidermolysis bullosa and the role of revertant mosaicism in therapeutic epidermal autografts. Despite its promise, phasing with long-read sequencing faces challenges, including low efficiency in enriching target regions and the inherent error rate of nanopore sequencing. Future developments in long-read sequencing technologies will be critical in overcoming these limitations and expanding the applicability of phasing across various clinical settings.</p>","PeriodicalId":54848,"journal":{"name":"Journal of Dermatology","volume":"52 3","pages":"392-399"},"PeriodicalIF":2.9000,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1346-8138.17597","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Dermatology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/1346-8138.17597","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"DERMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Phasing, the process of determining which alleles at different loci on homologous chromosomes belong together on the same chromosome, is crucial in the diagnosis and management of autosomal recessive diseases. Advances in long-read sequencing technologies have significantly enhanced our ability to accurately determine haplotypes. This review discusses the application of low-coverage long-read sequencing, nanopore Cas9-guided long-read sequencing, and adaptive sampling in phasing, highlighting their utility in complex clinical scenarios. Through clinical vignettes, we explore the importance of phasing in gene therapy design for recessive dystrophic epidermolysis bullosa and the role of revertant mosaicism in therapeutic epidermal autografts. Despite its promise, phasing with long-read sequencing faces challenges, including low efficiency in enriching target regions and the inherent error rate of nanopore sequencing. Future developments in long-read sequencing technologies will be critical in overcoming these limitations and expanding the applicability of phasing across various clinical settings.
期刊介绍:
The Journal of Dermatology is the official peer-reviewed publication of the Japanese Dermatological Association and the Asian Dermatological Association. The journal aims to provide a forum for the exchange of information about new and significant research in dermatology and to promote the discipline of dermatology in Japan and throughout the world. Research articles are supplemented by reviews, theoretical articles, special features, commentaries, book reviews and proceedings of workshops and conferences.
Preliminary or short reports and letters to the editor of two printed pages or less will be published as soon as possible. Papers in all fields of dermatology will be considered.