Linkage and association analysis of CACNG3 in childhood absence epilepsy
| Autor: | Anna-Elina Lehesjoki, Olivier Dulac, Orvar Eeg-Olofsson, Andrew Makoff, Athanasios Covanis, Armin Heils, Françoise Goutières, Petra M.C. Callenbach, Jean Aicardi, Oebele F. Brouwer, Kate V. Everett, Marianne J. Kjeldsen, Rima Nabbout, Robert Robinson, Mark Gardiner, M Rees, Auli Siren, Paul M. McKeigue, Martha Feucht, Barry A. Chioza, Renzo Guerrini, M. L. Friis, Harald N. Aschauer, Thomas Sander, Nichole Taske, Ingrid Olsson |
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| Přispěvatelé: | Faculteit Medische Wetenschappen/UMCG |
| Rok vydání: | 2007 |
| Předmět: |
Male
CACNG3 Linkage disequilibrium VARIANTS MOUSE Linkage Disequilibrium Calcium Channels T-Type 0302 clinical medicine CHANNEL Locus heterogeneity Genetics (clinical) Genetics 0303 health sciences splice variants GENETIC-VARIATION Chromosome Mapping Pedigree RECEPTORS absence epilepsy CACNA1H Female linkage Genetic Markers PEDIGREE DISEQUILIBRIUM TEST Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Article Idiopathic generalized epilepsy 03 medical and health sciences Childhood absence epilepsy Seizures Genetic linkage medicine Humans Genetic Predisposition to Disease 030304 developmental biology Genetic association MUTATIONS association medicine.disease Epilepsy Absence biology.protein SEIZURES Calcium Channels IDIOPATHIC GENERALIZED EPILEPSY Chromosomes Human Pair 16 030217 neurology & neurosurgery Microsatellite Repeats |
| Zdroj: | Everett, K V, Chioza, B, Aicardi, J, Aschauer, H, Brouwer, O, Callenbach, P, Covanis, A, Dulac, O, Eeg-Olofsson, O, Feucht, M, Friis, M, Goutieres, F, Guerrini, R, Heils, A, Kjeldsen, M, Lehesjoki, A-E, Makoff, A, Nabbout, R, Olsson, I, Sander, T, Sirén, A, McKeigue, P, Robinson, R, Taske, N, Rees, M & Gardiner, M 2007, ' Linkage and association analysis of CACNG3 in childhood absence epilepsy ', European Journal of Human Genetics, vol. 15, no. 4, pp. 463-72 . https://doi.org/10.1038/sj.ejhg.5201783 European Journal of Human Genetics, 15(4), 463-472. Nature Publishing Group |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/sj.ejhg.5201783 |
| Popis: | Udgivelsesdato: April Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy characterised by absence seizures manifested by transitory loss of awareness with 2.5-4 Hz spike-wave complexes on ictal EEG. A genetic component to aetiology is established but the mechanism of inheritance and the genes involved are not fully defined. Available evidence suggests that genes encoding brain expressed voltage-gated calcium channels, including CACNG3 on chromosome 16p12-p13.1, may represent susceptibility loci for CAE. The aim of this work was to further evaluate CACNG3 as a susceptibility locus by linkage and association analysis. Assuming locus heterogeneity, a significant HLOD score (HLOD = 3.54, alpha = 0.62) was obtained for markers encompassing CACNG3 in 65 nuclear families with a proband with CAE. The maximum non-parametric linkage score was 2.87 (P < 0.002). Re-sequencing of the coding exons in 59 patients did not identify any putative causal variants. A linkage disequilibrium (LD) map of CACNG3 was constructed using 23 single nucleotide polymorphisms (SNPs). Transmission disequilibrium was sought using individual SNPs and SNP-based haplotypes with the pedigree disequilibrium test in 217 CAE trios and the 65 nuclear pedigrees. Evidence for transmission disequilibrium (P < or = 0.01) was found for SNPs within a approximately 35 kb region of high LD encompassing the 5'UTR, exon 1 and part of intron 1 of CACNG3. Re-sequencing of this interval was undertaken in 24 affected individuals. Seventy-two variants were identified: 45 upstream; two 5'UTR; and 25 intronic SNPs. No coding sequence variants were identified, although four variants are predicted to affect exonic splicing. This evidence supports CACNG3 as a susceptibility locus in a subset of CAE patients. |
| Databáze: | OpenAIRE |
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