Long‐read HiFi sequencing of NUDT15 : Phased full‐gene haplotyping and pharmacogenomic allele discovery
| العنوان: | Long‐read HiFi sequencing of NUDT15 : Phased full‐gene haplotyping and pharmacogenomic allele discovery |
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| المؤلفون: | Erick R. Scott, Yao Yang, Mariana R. Botton, Yoshinori Seki, Keito Hoshitsuki, John Harting, Primo Baybayan, Neal Cody, Paola Nicoletti, Takaya Moriyama, Shreyasee Chakraborty, Jun J. Yang, Lisa Edelmann, Eric E. Schadt, Jonas Korlach, Stuart A. Scott |
| المصدر: | Human Mutation. 43:1557-1566 |
| بيانات النشر: | Hindawi Limited, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Genotype, Haplotypes, Pharmacogenetics, Genetics, Humans, Sequence Analysis, DNA, Alleles, Genetics (clinical) |
| الوصف: | To determine the phase of NUDT15 sequence variants for more comprehensive star (*) allele diplotyping, we developed a novel long-read single-molecule real-time HiFi amplicon sequencing method. A 10.5 kb NUDT15 amplicon assay was validated using reference material positive controls and additional samples for specimen type and blinded accuracy assessment. Triplicate NUDT15 HiFi sequencing of two reference material samples had nonreference genotype concordances of99.9%, indicating that the assay is robust. Notably, short-read genome sequencing of a subset of samples was unable to determine the phase of star (*) allele-defining NUDT15 variants, resulting in ambiguous diplotype results. In contrast, long-read HiFi sequencing phased all variants across the NUDT15 amplicons, including a *2/*9 diplotype that previously was characterized as *1/*2 in the 1000 Genomes Project v3 data set. Assay throughput was also tested using 8.5 kb amplicons from 100 Ashkenazi Jewish individuals, which identified a novel NUDT15 *1 suballele (c.-121GA) and a rare likely deleterious coding variant (p.Pro129Arg). Both novel alleles were Sanger confirmed and assigned as *1.007 and *20, respectively, by the PharmVar Consortium. Taken together, NUDT15 HiFi amplicon sequencing is an innovative method for phased full-gene characterization and novel allele discovery, which could improve NUDT15 pharmacogenomic testing and subsequent phenotype prediction. |
| تدمد: | 1098-1004 1059-7794 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4f406ff4b322204b3cd3c5d435891ee5 https://doi.org/10.1002/humu.24457 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....4f406ff4b322204b3cd3c5d435891ee5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10981004 10597794 |
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