Disease relevance of CHRNA7

• A previous study of 34 nuclear pedigrees segregating juvenile myoclonic epilepsy (JME) gave significant evidence of linkage with heterogeneity to marker loci on chromosome 15q13-14 close to the candidate gene CHRNA7 (Hum. Mol. Genet. 6 (1997) 1329) [1].
• The aim of this work was to further evaluate the putative aetiological role of CHRNA7 in JME within the 34 families originally described, and to assess the contribution of this locus to a broader phenotype of idiopathic generalised epilepsy (IGE) [1].

Psychiatry related information on CHRNA7

• A second large family with catatonic schizophrenia supports the region distally of CHRNA7 on chromosome 15q14-15 [2].
• Therefore, members of a large family with periodic catatonia strongly supporting the chromosome 15q13-22 region were genotyped with polymorphic markers localized around the CHRNA7 locus [3].
• The human alpha7 nicotinic acetylcholine receptor subunit (CHRNA7) gene cluster maps to the chromosome 15q13-q14 and is implicated as a candidate gene for bipolar disorder (BPD) by genetic linkage study [4].

High impact information on CHRNA7

• CONTEXT: The alpha7 nicotinic acetylcholine receptor gene, CHRNA7, is associated with genetic transmission of schizophrenia and related cognitive and neurophysiological sensory gating deficits [5].
• CONCLUSIONS: Although linkage disequilibrium with other genetic alterations cannot be excluded, the CHRNA7 core promoter variants, found in this study, may contribute to a common pathophysiologic feature of schizophrenia [6].
• This study presents DNA sequence analysis of the core promoter region for CHRNA7 in schizophrenic and control subjects [6].
• BACKGROUND: The alpha7 neuronal nicotinic acetylcholine receptor subunit gene (CHRNA7) has been implicated as a candidate gene for schizophrenia, and for an auditory sensory processing deficit found in the disease, by both genetic linkage at 15q14 and biochemical data [6].
• Significant evidence for linkage with heterogeneity was found to polymorphic loci encompassing the region in which the gene encoding the alpha7 subunit of nAChR (CHRNA7) maps on chromosome 15q14 (HLOD = 4.4 at alpha = 0.65; Z(all) = 2.94, P = 0.0005) [7].

Biological context of CHRNA7

• For severity of nicotine dependence, two SNPs in CHRNA7 (rs1909884 and rs883473), one SNP in CHRNA5 (rs680244) and the interaction of a SNP in CHRNA7 (rs2337980) with neuroticism, were included in the model (P=2.24 x 10(-7), Nagelkerke r(2)=0.40) [8].
• Multipoint linkage analysis and intrafamilial association studies were performed with microsatellite markers that encompass both CHRNA7 and its partial duplication (CHRFAM7A) [1].
• Mutation screening of the CHRNA7 gene (and consequently exons 5-10 of CHRFAM7A) and its putative promoter sequence identified a total of 13 sequence variants across 23 of 34 JME-affected families [1].
• Two types of genetic variation, a large deletion and a -2 base-pair deletion in exon 6 resulting in a truncation of the open reading frame, affect specifically the CHRNA7-like gene [9].
• Two related alpha 7 genes (CHRNA7 and CHRNA7-like gene) resulting from a partial duplication (from exon 5 to exon 10) are present in the human genome [9].

Anatomical context of CHRNA7

• METHOD: CHRNA7 and CHRFAM7A mRNA levels were measured in postmortem prefrontal cortex (donated by the Stanley Foundation) from subjects with schizophrenia, bipolar disorder and unaffected controls (n = 35 each) [10].

Other interactions of CHRNA7

• Our present study provided the first line of direct evidence suggesting that the CHRM5 gene combined with the CHRNA7 gene may be linked to schizophrenia [11].
• Of these, the greatest support exists for the DRD3 (3q13.3), HTR2A (13q14.2), and CHRNA7 (15q13-q14) genes [12].
• However, it remains possible that the CHRNA7 gene and other nicotinic system genes may be involved in conferring susceptibility to ADHD [13].
• Following these findings, we examined three polymorphic markers (D15S1360, L76630, and ACTC) on chromosome 15q13-14 near the CHRNA7 gene for linkage to schizophrenia, using 54 pedigrees from an independent study [14].
• In linkage analysis concerning familial centrotemporal spikes and sharp waves (CTS) and benign rolandic epilepsy, evidence for linkage was found to a region on chromosome 15q14, close to the alpha-7 subunit gene of the neuronal nicotinic acetylcholine receptor (CHRNA7) [15].

Analytical, diagnostic and therapeutic context of CHRNA7

• Molecular cloning and chromosomal localization of the human alpha 7-nicotinic receptor subunit gene (CHRNA7) [16].
• Single strand conformation polymorphism (SSCP) and sequence analyses of DNA from schizophrenic and control individuals identified 33 variants in the coding region and intron/exon borders of the CHRNA7 gene and its partial duplication, dupCHRNA7; common polymorphisms were mapped [17].

References