No association ofDYNC1H1with sporadic ALS in a case‐control study of a northern European derived population: A tagging SNP approach
- 1 January 2006
- journal article
- research article
- Published by Taylor & Francis in Amyotrophic Lateral Sclerosis
- Vol. 7 (1) , 46-56
- https://doi.org/10.1080/14660820500397057
Abstract
The cytoplasmic dynein-dynactin complex has been implicated in the aetiology of motor neuron degeneration in both mouse models and human forms of motor neuron disease. We have previously shown that mutations in the cytoplasmic dynein 1 heavy chain 1 gene (Dync1h1) are causal in a mouse model of late-onset motor neuron degeneration but have found no association of the homologous sites in human DYNC1H1 with human motor neuron disease. Here we extend these analyses to investigate the DYNC1H1 genomic locus to determine if it is associated with sporadic amyotrophic lateral sclerosis (ALS) in a northern European-derived population. Among the 16 single nucleotide polymorphisms (SNPs) we examined, just two SNPs (rs2251644 and rs941793) were sufficient to tag the majority of haplotypic variation (r2 > or = 0.85) and these were tested in a case-control association study with 266 North American sporadic ALS patients and 225 matched controls. We found no association between genetic variation at DYNC1H1 and sporadic ALS (rs2251644; p = 0.538, rs941793; p = 0.204, haplotype; p = 0.956). In addition we investigated patterns of diversity at DYNC1H1 in Japanese and Cameroonian populations to establish the evolutionary history for this gene and observed reduced genetic diversity in the northern Europeans suggestive of selection at this locus.Keywords
This publication has 38 references indexed in Scilit:
- A survey of haplotype variants at several disease candidate genes: the importance of rare variants for complex diseasesJournal of Medical Genetics, 2005
- The common variants/multiple disease hypothesis of common complex genetic disordersMedical Hypotheses, 2004
- Genome scans and candidate gene approaches in the study of common diseases and variable drug responsesTrends in Genetics, 2003
- Selection and Evaluation of Tagging SNPs in the Neuronal-Sodium-Channel Gene SCN1A: Implications for Linkage-Disequilibrium Gene MappingAmerican Journal of Human Genetics, 2003
- Signatures of natural selection in the human genomeNature Reviews Genetics, 2003
- Positive results in association studies are associated with departure from Hardy-Weinberg equilibrium: hint for genotyping error?Human Genetics, 2002
- Trimming, Weighting, and Grouping SNPs in Human Case-Control Association StudiesGenome Research, 2001
- Monte Carlo tests for associations between disease and alleles at highly polymorphic lociAnnals of Human Genetics, 1995
- Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosisNature, 1993
- Analysis of Gene Diversity in Subdivided PopulationsProceedings of the National Academy of Sciences, 1973