Evidence for the modality independence of the genetic epistasis between the dopaminergic and cholinergic system on working memory capacity
EUROPEAN NEUROPSYCHOPHARMACOLOGY
Authors: Markett, Sebastian; Montag, Christian; Walter, Nora T.; Reuter, Martin
Abstract
Working memory (WM) is fractionated into systems for visuospatial and phonological information. Recently, it has been shown that the dopamine d2 receptor gene DRD2 and CHRNA4, the gene coding for the nicotinic acetylcholine receptors alpha4 subunit, interact epistatically on visuospatial WM capacity. In the present study, we show a similar interaction on phonological WM capacity in N=137 healthy subjects genotyped for two single nucleotide polymorphisms (DRD2 rs6277 and CHRNA4 rs1044396). Given the functional independence of the two systems we hypothesize that the genetic interaction targets the central executive which is the common control process for both systems. (C) 2010 Elsevier B.V. and ECNP. All rights reserved.
Characterization of the genomic structure of the human neuronal nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster and identification of novel intragenic polymorphisms
JOURNAL OF HUMAN GENETICS
Authors: Duga, S; Solda, G; Asselta, R; Bonati, MT; Dalpra, L; Malcovati, M; Tenchini, ML
Abstract
Genes coding for the alpha5, alpha3, and beta4 subunits (CHRNA5, CHRNA3, and CHRNB4) of the neuronal nicotinic acetylcholine receptors (nAChRs) are clustered on chromosome 15q24. Linkage of this chromosomal region to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), an idiopathic partial epilepsy, was reported in one family. Moreover, mutations in other neuronal nAChR subunit genes coding for the alpha4 (CHRNA4) and the beta2 (CHRNB2) subunits were associated with ADNFLE. Apart from the exon-intron structure of CHRNA3, the genomic organization of this gene cluster was unknown, making comprehensive mutational analyses impossible. The genomic structure of CHRNA5 and CHRNB4 is here reported. Moreover, two hitherto unknown introns were identified within the 3' untranslated region of CHRNA3, causing a partial tail-to-tail overlap with CHRNA5. Four novel intragenic polymorphisms were identified and characterized in the cluster.