ArticleAmerican journal of human genetics2009
CAG expansion in the Huntington disease gene is associated with a specific and targetable predisposing haplogroup.
Article in American journal of human genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
119 citing papers in PubMed, 3 syntheses or guidelines pooled it, 238 citations in OpenAlex.
- Variation in the reported prevalence of Huntington's disease: a systematic review and guide to interpretation.Journal of neurology · 2025Pooled it
- Machado-Joseph disease in Brazil and other South American countries: A systematic Review and Meta-analysis of Prevalence, CAG Repeat Lengths, Age At Onset, and Ancestry.Cerebellum (London, England) · 2025Pooled it
- Distribution of theClinical medicine & research · 2020Pooled it
- Population-scale disease-associated tandem repeat analysis reveals locus and ancestry-specific insights.Nature communications · 2026Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Development of Antisense Gapmers for the Treatment of Huntington's Disease.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Computational Framework for High Copy-Number Probe Selection and Cross-Binding Reduction.Analytical science advances · 2025Article
- Review
- Emerging Roles of Bile Acids in Neuroinflammation.International journal of molecular sciences · 2025Review
- Brain Connectivity, Neural Networks, and Resilience in Aging and Neurodegeneration.The American journal of pathology · 2025Review
- Nucleotide-Specific RNA Conformations and Dynamics as Precursors to Ribonucleoprotein Condensates.Journal of the American Chemical Society · 2025Article
- Dysregulation of miRNAs in Sicilian Patients with Huntington's Disease.Diagnostics (Basel, Switzerland) · 2025Article
- DurableMolecular therapy. Nucleic acids · 2025Article
- Rare Diseases, Spotlighting Amyotrophic Lateral Sclerosis, Huntington's Disease, and Myasthenia Gravis: Insights from Landscape Analysis of Current Research.Biochemistry · 2025Review
- Broken but not beaten: Challenge of reducing the amyloids pathogenicity by degradation.Journal of advanced research · 2025Review
- Analysis of short tandem repeats linked to polyglutamine diseases from whole-genome sequencing reveals intermediate alleles ofBrain communications · 2025Article
- Advances on the Mechanisms and Therapeutic Strategies in Non-coding CGG Repeat Expansion Diseases.Molecular neurobiology · 2024Review
- Exploring molecular mechanisms, therapeutic strategies, and clinical manifestations of Huntington's disease.Archives of pharmacal research · 2024Review
- Latest advances on new promising molecular-based therapeutic approaches for Huntington's disease.Journal of translational internal medicine · 2024Article
- Mitochondrial Dysfunction: A Key Player in Brain Aging and Diseases.Current issues in molecular biology · 2024Review
59 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Huntington disease (HD) is an autosomal-dominant disorder that results from >or=36 CAG repeats in the HD gene (HTT). Approximately 10% of patients inherit a chromosome that underwent CAG expansion from an unaffected parent with <36 CAG repeats. This study is a comprehensive analysis of genetic diversity in HTT and reveals that HD patients of European origin (n = 65) have a significant enrichment (95%) of a specific set of 22 tagging single nucleotide polymorphisms (SNPs) that constitute a single haplogroup. The disease association of many SNPs is much stronger than any previously reported polymorphism and was confirmed in a replication cohort (n = 203). Importantly, the same haplogroup is also significantly enriched (83%) in individuals with 27-35 CAG repeats (intermediate alleles, n = 66), who are unaffected by the disease, but have increased CAG tract sizes relative to the general population (n = 116). These data support a stepwise model for CAG expansion into the affected range (>or=36 CAG) and identifies specific haplogroup variants in the general population associated with this instability. The specific variants at risk for CAG expansion are not present in the general population in China, Japan, and Nigeria where the prevalence of HD is much lower. The current data argue that cis-elements have a major predisposing influence on CAG instability in HTT. The strong association between specific SNP alleles and CAG expansion also provides an opportunity of personalized therapeutics in HD where the clinical development of only a small number of allele-specific targets may be sufficient to treat up to 88% of the HD patient population.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.