TY - JOUR
T1 - Characterization of the genomic structure of the human neuronal nicotinic acetylcholine receptor CHRNA5/A3/B4 gene cluster and identification of novel intragenic polymorphisms
AU - Duga, S.
AU - Soldà, G.
AU - Asselta, R.
AU - Bonati, M. T.
AU - Dalprà, L.
AU - Malcovati, M.
AU - Tenchini, M. L.
PY - 2001
Y1 - 2001
N2 - Genes coding for the α5, α3, and β4 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 α4 (CHRNA4) and the β2 (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.
AB - Genes coding for the α5, α3, and β4 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 α4 (CHRNA4) and the β2 (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.
KW - Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)
KW - CHRNA5/A3/B4 gene cluster
KW - Genomic structure
KW - Human neuronal nicotinic acetylcholine receptor (nAChR)
KW - Polymorphisms
KW - Tail-to-tail overlap
UR - http://www.scopus.com/inward/record.url?scp=0035211660&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035211660&partnerID=8YFLogxK
U2 - 10.1007/s100380170015
DO - 10.1007/s100380170015
M3 - Article
C2 - 11721883
AN - SCOPUS:0035211660
VL - 46
SP - 640
EP - 648
JO - Journal of Human Genetics
JF - Journal of Human Genetics
SN - 1434-5161
IS - 11
ER -