Genomewide scans in North American families reveal genetic linkage of essential tremor to a region on chromosome 6p23
| العنوان: | Genomewide scans in North American families reveal genetic linkage of essential tremor to a region on chromosome 6p23 |
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| المؤلفون: | Jay Ji, Aleksey Shatunov, Yiping Zhang, Ayush Dagvadorj, Hee Suk Lee, Nyamkhishig Sambuughin, Andrew B. Singleton, Joseph Jankovic, Rodger J. Elble, John Hardy, Lev G. Goldfarb, Virginia Kimonis, Mark Hallett |
| المصدر: | Brain. 129:2318-2331 |
| بيانات النشر: | Oxford University Press (OUP), 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Adult, Genetic Markers, Male, Genotype, Genetic Linkage, DNA Mutational Analysis, Locus (genetics), Biology, Genetic linkage, Tremor, Humans, Coding region, Genetic Predisposition to Disease, Age of Onset, Gene, Family Health, Genetics, Haplotype, Chromosome Mapping, Chromosome, Middle Aged, United States, Complete linkage, Pedigree, Dystonia, Phenotype, Haplotypes, Genetic marker, Chromosomes, Human, Pair 6, Female, Neurology (clinical), Microsatellite Repeats |
| الوصف: | Essential tremor (ET) is the most prevalent adult-onset movement disorder showing evidence of non-random accumulation in some families. ET has previously been mapped to genetic loci on chromosomes 2p and 3q, but no causative genes identified. We conducted genomewide linkage screening with subsequent fine mapping in seven large North American families comprising a total of 325 genotyped individuals that included 65 patients diagnosed as definite ET. Linkage analysis was based on methodology implemented in SimWalk2 and LINKAGE programs. A multigenerational family revealed suggestive linkage to a locus on chromosome 6p23 with maximal nonparametric linkage (NPL) multipoint score 3.281 (P = 0.0005) and parametric multipoint log of the odds (LOD) score 2.983. A second family showed positive linkage to the same 6p23 region with a maximal NPL score 2.125 (P = 0.0075) and LOD score 1.265. Haplotype analysis led to the identification of a 600 kb interval shared by both families. Sequencing of coding regions of 15 genes located in the linked region detected numerous sequence variants, some of them predicting a change of the encoded amino acid, but each was also found in controls. Our findings provide evidence for linkage to a novel susceptibility locus on chromosome 6p23. Analysis of additional ET-affected families is needed to confirm linkage and identify the underlying gene. |
| تدمد: | 1460-2156 0006-8950 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::febb8c8e8bc30eb275032e70b1e07813Test https://doi.org/10.1093/brain/awl120Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....febb8c8e8bc30eb275032e70b1e07813 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602156 00068950 |
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