Genotyping single nucleotide polymorphisms for allele-selective therapy in Huntington disease
| العنوان: | Genotyping single nucleotide polymorphisms for allele-selective therapy in Huntington disease |
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| المؤلفون: | Mary Edmondson, Mark S. LeDoux, H. Diana Rosas, Vicki L. Wheelock, Michael A. Panzara, E. Ray Dorsey, Nenad Svrzikapa, Kenneth Longo, Jaya Goyal, Sandra K. Kostyk, Francis O. Walker, Jody Corey-Bloom, Serena Hung, Ralf Reilmann, Daniel O. Claassen |
| المصدر: | Neurology: Genetics Neurology. Genetics, vol 6, iss 3 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Huntington's Disease, Genetics, congenital, hereditary, and neonatal diseases and abnormalities, Mutant, Neurosciences, Single-nucleotide polymorphism, Disease, Neurodegenerative, Biology, Article, Brain Disorders, nervous system diseases, Loss of heterozygosity, Rare Diseases, Huntingtin Gene, mental disorders, Neurology (clinical), Allele, Trinucleotide repeat expansion, Genotyping, Genetics (clinical) |
| الوصف: | BackgroundThe huntingtin gene (HTT) pathogenic cytosine-adenine-guanine (CAG) repeat expansion responsible for Huntington disease (HD) is phased with single nucleotide polymorphisms (SNPs), providing targets for allele-selective treatments.ObjectiveThis prospective observational study defined the frequency at which rs362307 (SNP1) or rs362331 (SNP2) was found on the same allele with pathogenic CAG expansions.MethodsAcross 7 US sites, 202 individuals with HD provided blood samples that were processed centrally to determine the number and size of CAG repeats, presence and heterozygosity of SNPs, and whether SNPs were present on the mutant HTT allele using long-read sequencing and phasing.ResultsHeterozygosity of SNP1 and/or SNP2 was identified in 146 (72%) individuals. The 2 polymorphisms were associated only with the mHTT allele in 61% (95% high density interval: 55%, 67%) of individuals.ConclusionsThese results are consistent with previous reports and demonstrate the feasibility of genotyping, phasing, and targeting of HTT SNPs for personalized treatment of HD. |
| وصف الملف: | application/pdf |
| تدمد: | 2376-7839 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f7f5f3f8d8167346914b9ab104beb78c https://doi.org/10.1212/nxg.0000000000000430 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f7f5f3f8d8167346914b9ab104beb78c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23767839 |
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