دورية أكاديمية
Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing
| العنوان: | Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing |
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| المؤلفون: | Stevanovski I., Chintalaphani S. R., Gamaarachchi H., Ferguson J. M., Pineda S. S., Scriba C. K., Tchan M., Fung V., Ng K., Cortese A., Houlden H., Dobson-Stone C., Fitzpatrick L., Halliday G., Ravenscroft G., Davis M. R., Laing N. G., Fellner A., Kennerson M., Kumar K. R., Deveson I. W. |
| المساهمون: | Stevanovski, I., Chintalaphani, S. R., Gamaarachchi, H., Ferguson, J. M., Pineda, S. S., Scriba, C. K., Tchan, M., Fung, V., Ng, K., Cortese, A., Houlden, H., Dobson-Stone, C., Fitzpatrick, L., Halliday, G., Ravenscroft, G., Davis, M. R., Laing, N. G., Fellner, A., Kennerson, M., Kumar, K. R., Deveson, I. W. |
| سنة النشر: | 2022 |
| المجموعة: | IRIS UNIPV (Università degli studi di Pavia) |
| مصطلحات موضوعية: | DNA, Copy Number Variation, Whole Genome Sequencing |
| الوصف: | More than 50 neurological and neuromuscular diseases are caused by short tandem repeat (STR) expansions, with 37 different genes implicated to date. We describe the use of programmable targeted long-read sequencing with Oxford Nanopore's ReadUntil function for parallel genotyping of all known neuropathogenic STRs in a single assay. Our approach enables accurate, haplotype-resolved assembly and DNA methylation profiling of STR sites, from a list of predetermined candidates. This correctly diagnoses all individuals in a small cohort (n = 37) including patients with various neurogenetic diseases (n = 25). Targeted long-read sequencing solves large and complex STR expansions that confound established molecular tests and short-read sequencing and identifies noncanonical STR motif conformations and internal sequence interruptions. We observe a diversity of STR alleles of known and unknown pathogenicity, suggesting that long-read sequencing will redefine the genetic landscape of repeat disorders. Last, we show how the inclusion of pharmacogenomic genes as secondary ReadUntil targets can further inform patient care. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | STAMPA |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/35245110; info:eu-repo/semantics/altIdentifier/wos/WOS:000790020300018; volume:8; issue:9; firstpage:eabm5386; journal:SCIENCE ADVANCES; http://hdl.handle.net/11571/1452247Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85125804052 |
| DOI: | 10.1126/sciadv.abm5386 |
| DOI: | 10.1126/sciadv.abm5386?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub++0pubmed& |
| الإتاحة: | https://doi.org/10.1126/sciadv.abm5386Test http://hdl.handle.net/11571/1452247Test |
| رقم الانضمام: | edsbas.B927CB0D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1126/sciadv.abm5386 |
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