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Article: Haplotype and linkage disequilibrium analysis to characterise a region in the calcium channel gene CACNA1A associated with idiopathic generalised epilepsy

TitleHaplotype and linkage disequilibrium analysis to characterise a region in the calcium channel gene CACNA1A associated with idiopathic generalised epilepsy
Authors
Issue Date2002
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ejhg
Citation
European Journal Of Human Genetics, 2002, v. 10 n. 12, p. 857-864 How to Cite?
AbstractIdiopathic generalised epilepsy (IGE) is a common form of epilepsy, including several defined and overlapping syndromes, and likely to be due to the combined actions of mutations in several genes. In a recent study we investigated the calcium channel gene CACNA1A for involvement in IGE, unselected for syndrome, by means of association studies using several polymorphisms within the gene. We reported a highly significant case/control association with a silent single nucleotide polymorphism (SNP) in exon 8 that we confirmed by within-family analyses. In this present study we screened the gene for novel SNPs within 25 kb of exon 8, which have enabled us to define the critical region of CACNA1A in predisposing to IGE. Several intronic SNPs were identified and three, within 1.5 kb of exon 8 and in strong linkage disequilibrium with each other and with the original SNP, were significantly associated with IGE (P=0.00029, P=0.0015 and P=0.010). The associations were not limited to an IGE syndrome or other subgroup. Another SNP, 25 kb away, in intron 6 was also significantly associated with IGE (P=0.0057) but is not in linkage disequilibrium with the SNPs around exon 8. Haplotype predictions revealed even more significant associations (3-marker haplotype: P < 10-6). Logistic regression showed that all the data can be explained by two of the SNPs, which is consistent with two functionally significant variants being responsible for all five associations, although a single variant cannot be excluded. The functionally significant variant(s) are unlikely to be exonic and suggests an effect on expression or alternative splicing.
Persistent Identifierhttp://hdl.handle.net/10722/175872
ISSN
2015 Impact Factor: 4.58
2015 SCImago Journal Rankings: 2.077
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChioza, Ben_US
dc.contributor.authorOseiLah, Aen_US
dc.contributor.authorNashef, Len_US
dc.contributor.authorSuarezMerino, Ben_US
dc.contributor.authorWilkie, Hen_US
dc.contributor.authorSham, Pen_US
dc.contributor.authorKnight, Jen_US
dc.contributor.authorAsherson, Pen_US
dc.contributor.authorMakoff, AJen_US
dc.date.accessioned2012-11-26T09:01:57Z-
dc.date.available2012-11-26T09:01:57Z-
dc.date.issued2002en_US
dc.identifier.citationEuropean Journal Of Human Genetics, 2002, v. 10 n. 12, p. 857-864en_US
dc.identifier.issn1018-4813en_US
dc.identifier.urihttp://hdl.handle.net/10722/175872-
dc.description.abstractIdiopathic generalised epilepsy (IGE) is a common form of epilepsy, including several defined and overlapping syndromes, and likely to be due to the combined actions of mutations in several genes. In a recent study we investigated the calcium channel gene CACNA1A for involvement in IGE, unselected for syndrome, by means of association studies using several polymorphisms within the gene. We reported a highly significant case/control association with a silent single nucleotide polymorphism (SNP) in exon 8 that we confirmed by within-family analyses. In this present study we screened the gene for novel SNPs within 25 kb of exon 8, which have enabled us to define the critical region of CACNA1A in predisposing to IGE. Several intronic SNPs were identified and three, within 1.5 kb of exon 8 and in strong linkage disequilibrium with each other and with the original SNP, were significantly associated with IGE (P=0.00029, P=0.0015 and P=0.010). The associations were not limited to an IGE syndrome or other subgroup. Another SNP, 25 kb away, in intron 6 was also significantly associated with IGE (P=0.0057) but is not in linkage disequilibrium with the SNPs around exon 8. Haplotype predictions revealed even more significant associations (3-marker haplotype: P < 10-6). Logistic regression showed that all the data can be explained by two of the SNPs, which is consistent with two functionally significant variants being responsible for all five associations, although a single variant cannot be excluded. The functionally significant variant(s) are unlikely to be exonic and suggests an effect on expression or alternative splicing.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ejhgen_US
dc.relation.ispartofEuropean Journal of Human Geneticsen_US
dc.subject.meshAdolescenten_US
dc.subject.meshAdulten_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshCalcium Channels - Geneticsen_US
dc.subject.meshChilden_US
dc.subject.meshChild, Preschoolen_US
dc.subject.meshChromatography, High Pressure Liquiden_US
dc.subject.meshDna Mutational Analysisen_US
dc.subject.meshEpilepsy, Generalized - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Frequencyen_US
dc.subject.meshHaplotypes - Geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshLinkage Disequilibrium - Geneticsen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshMolecular Sequence Dataen_US
dc.titleHaplotype and linkage disequilibrium analysis to characterise a region in the calcium channel gene CACNA1A associated with idiopathic generalised epilepsyen_US
dc.typeArticleen_US
dc.identifier.emailSham, P: pcsham@hku.hken_US
dc.identifier.authoritySham, P=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.ejhg.5200896en_US
dc.identifier.pmid12461694-
dc.identifier.scopuseid_2-s2.0-0036922940en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036922940&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume10en_US
dc.identifier.issue12en_US
dc.identifier.spage857en_US
dc.identifier.epage864en_US
dc.identifier.isiWOS:000179907100012-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridChioza, B=6603239784en_US
dc.identifier.scopusauthoridOseiLah, A=6506643178en_US
dc.identifier.scopusauthoridNashef, L=7003977875en_US
dc.identifier.scopusauthoridSuarezMerino, B=6507936903en_US
dc.identifier.scopusauthoridWilkie, H=6603081327en_US
dc.identifier.scopusauthoridSham, P=34573429300en_US
dc.identifier.scopusauthoridKnight, J=13002769800en_US
dc.identifier.scopusauthoridAsherson, P=35402700900en_US
dc.identifier.scopusauthoridMakoff, AJ=7006063526en_US
dc.identifier.citeulike7679366-

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