ArticleAmerican journal of human genetics2019
A Comprehensive Haplotype-Targeting Strategy for Allele-Specific HTT Suppression in Huntington Disease.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Distribution of theClinical medicine & research · 2020Pooled it
- Double strand breaks drive toxicity in a Huntington's disease mouse model with or without somatic expansion.Nature communications · 2026Article
- Molecular and imaging biomarker responses to brain mutant HTT lowering in a mouse model of Huntington disease.Molecular therapy. Nucleic acids · 2025Article
- Multivariate genome-wide association analysis of dyslexia and quantitative reading skill improves gene discovery.Translational psychiatry · 2025Article
- Double strand breaks drive toxicity in Huntington's disease mice with or without somatic expansion.bioRxiv : the preprint server for biology · 2025Article
- Latest advances on new promising molecular-based therapeutic approaches for Huntington's disease.Journal of translational internal medicine · 2024Article
- Spanish HTT gene study reveals haplotype and allelic diversity with possible implications for germline expansion dynamics in Huntington disease.Human molecular genetics · 2023Article
- Allele-specific quantitation of ATXN3 and HTT transcripts in polyQ disease models.BMC biology · 2023Article
- Haplotyping SNPs for allele-specific gene editing of the expanded huntingtin allele using long-read sequencing.HGG advances · 2023Article
- Chemical engineering of therapeutic siRNAs for allele-specific gene silencing in Huntington's disease models.Nature communications · 2022Article
- Towards Personalized Allele-Specific Antisense Oligonucleotide Therapies for Toxic Gain-of-Function Neurodegenerative Diseases.Pharmaceutics · 2022Review
- Haplotype-specific insertion-deletion variations for allele-specific targeting in Huntington's disease.Molecular therapy. Methods & clinical development · 2022Article
- Investigation of the Influence of TBP CAG/CAA Repeats in Conjunction with HTT CAG Repeats on Huntington's Disease Age at Onset in a Brazilian Sample.Journal of molecular neuroscience : MN · 2022Article
- Characterization of C9orf72 haplotypes to evaluate the effects of normal and pathological variations on its expression and splicing.PLoS genetics · 2021Article
- Tracing the mutated HTT and haplotype of the African ancestor who spread Huntington disease into the Middle East.Genetics in medicine : official journal of the American College of Medical Genetics · 2020Article
- Investigation of intermediate CAG alleles of the HTT in the general population of Rio de Janeiro, Brazil, in comparison with a sample of Huntington disease-affected families.Molecular genetics & genomic medicine · 2020Article
- Huntingtin Lowering Strategies.International journal of molecular sciences · 2020Review
- Review
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 6 countries.
Funding
Abstract
Huntington disease (HD) is a fatal neurodegenerative disorder caused by a gain-of-function mutation in HTT. Suppression of mutant HTT has emerged as a leading therapeutic strategy for HD, with allele-selective approaches targeting HTT SNPs now in clinical trials. Haplotypes associated with the HD mutation (A1, A2, A3a) represent panels of allele-specific gene silencing targets for efficient treatment of individuals with HD of Northern European and indigenous South American ancestry. Here we extend comprehensive haplotype analysis of the HD mutation to key populations of Southern European, South Asian, Middle Eastern, and admixed African ancestry. In each of these populations, the HD mutation occurs predominantly on the A2 HTT haplotype. Analysis of HD haplotypes across all affected population groups enables rational selection of candidate target SNPs for development of allele-selective gene silencing therapeutics worldwide. Targeting SNPs on the A1 and A2 haplotypes in parallel is essential to achieve treatment of the most HD-affected subjects in populations where HD is most prevalent. Current allele-specific approaches will leave a majority of individuals with HD untreated in populations where the HD mutation occurs most frequently on the A2 haplotype. We further demonstrate preclinical development of potent and selective ASOs targeting SNPs on the A2 HTT haplotype, representing an allele-specific treatment strategy for these individuals. On the basis of comprehensive haplotype analysis, we show the maximum proportion of HD-affected subjects that may be treated with three or four allele targets in different populations worldwide, informing current allele-specific HTT silencing strategies.
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Registered trials
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