| 1 | Am J Psychiatry 2006 Oct 163: 1832-4 |
|---|---|
| PMID | 17012698 |
| Title | Episodic memory performance predicted by the 2bp deletion in exon 6 of the "alpha 7-like" nicotinic receptor subunit gene. |
| Abstract | There is evidence of linkage between chromosome 15q14 and the P50 auditory evoked response, a heritable neuropsychological marker associated with increased risk of schizophrenia. Chromosome 15q14 harbors the alpha-7 nicotinic receptor subunit gene (CHRNA7) and a hybrid gene of unknown function (CHRFAM7A). CHRNA7 is involved in memory formation, a core dysfunction in schizophrenia. The authors set out to determine if this locus is associated with memory dysfunction in schizophrenia. A 2bp deletion in exon 6 of CHRFAM7A, which disrupts the hybrid gene and has previously been associated with P50 deficit, was genotyped in 251 individuals from the Maudsley Family Study of schizophrenia. Episodic memory function was assessed using the Wechsler Memory Scale. Significant associations were identified with delayed recall and percentage retained, with the presence of the deletion predicting worse performance. These observations indicate that episodic memory function is a schizophrenia endophenotype and implicate the CHRFAM7A/CHRNA7 locus in modulating its function. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Acta Psychiatr Scand 2006 Sep 114: 211-5 |
| PMID | 16889592 |
| Title | Regulation of alpha7-nicotinic receptor subunit and alpha7-like gene expression in the prefrontal cortex of patients with bipolar disorder and schizophrenia. |
| Abstract | The alpha7-nicotinic receptor subunit gene (CHRNA7) is located at chromosome 15q13-14, a region previously linked with schizophrenia. Genetic association and mRNA expression studies also implicate CHRNA7 in schizophrenia. The CHRNA7 gene has a partial duplication that constitutes the alpha7-like nicotinic receptor gene (CHRFAM7A). We hypothesized that major psychoses could affect the expression of both CHRNA7 and CHRFAM7A. 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). The mRNA levels of alpha7 and alpha7-like genes have a positive correlation overall (r = 0.25; P = 0.009), however, there is no significant difference in the expression of CHRNA7 among the three diagnostic groups. This correlation is driven by the bipolar group (r = 0.43; P = 0.009), and is absent in schizophrenia and unaffected controls, suggesting an alteration in the CHRNA7:CHRFAM7A ratio in bipolar disorder. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2006 Sep 141B: 571-5 |
| PMID | 16823804 |
| Title | Association study of CHRFAM7A copy number and 2 bp deletion polymorphisms with schizophrenia and bipolar affective disorder. |
| Abstract | schizophrenia and bipolar disorder are major psychiatric diseases that have a strong genetic element. Markers in the vicinity of the CHRNA7 gene at 15q13-q14 have been linked with an endophenotype of schizophrenia, P50 sensory gating disorder, with schizophrenia itself and with bipolar disorder. We have measured the copy number of the polymorphic partial duplication of CHRNA7 (CHRFAM7A) and genotyped a polymorphic 2 bp deletion within exon 6 of CHRFAM7A. In this study, 208 probands with a primary diagnosis of schizophrenia, 217 with a diagnosis of bipolar affective disorder and 28 with schizoaffective or other psychotic disorders were examined together with 197 controls recruited from the same region in Scotland. No significant association was seen for schizophrenia and bipolar disorder by genotype or allele overall for either polymorphism, but a mildly significant association by genotype (P = 0.04) was observed for absence of CHRFAM7A when the sample was analyzed as a single psychosis phenotype. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Neurosci. Res. 2007 Feb 57: 194-202 |
| PMID | 17113175 |
| Title | Linkage disequilibrium analysis of the CHRNA7 gene and its partially duplicated region in schizophrenia. |
| Abstract | Several previous studies have reported a significant linkage between markers in the alpha 7 nicotinic cholinergic receptor subunit (CHRNA7) gene and either schizophrenia or the P50 sensory gating deficit, a schizophrenia endophenotype. However, CHRFAM7A, a partially duplicated gene 1.6Mb upstream of the CHRNA7 gene, has complicated further genetic analysis. We genotyped 14 polymorphic markers throughout the full-length CHRNA7 gene and the duplicated region in 188 unrelated Han Chinese patients with schizophrenia and 188 controls. The duplicated regions were assessed by genotyping up- and down-stream polymorphic markers in the vicinity of each region and analyzing the linkage disequilibrium (LD) between each pair of markers. No evidence of risk variants for schizophrenia in either the CHRNA7 gene or the partially duplicated region was found in the LD analysis. A significant deviation from the Hardy-Weinberg equilibrium (HWE) was found only in the genotypic distribution of SNP9 (IVS4-1912) in patients (p=0.00829), but not in controls. In conclusion, our LD analysis did not reveal any association between schizophrenia in our Han Chinese population and the CHRNA7 gene or its partially duplicated region. However, we could not exclude the possibility of a weak genetic effect due to the small sample size. Analyses of larger samples and higher-density markers, particularly around SNP9 (IVS4-1912), are still needed. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Eur. J. Hum. Genet. 2008 Nov 16: 1364-71 |
| PMID | 18545269 |
| Title | The copy number variant involving part of the alpha7 nicotinic receptor gene contains a polymorphic inversion. |
| Abstract | The alpha7 nicotinic acetylcholine receptor gene (CHRNA7) is located at 15q13-q14 in a region that is strongly linked to the P50 sensory gating deficit, an endophenotype of schizophrenia and bipolar disorder. Part of the gene is a copy number variant, due to a duplication of exons 5-10 and 3' sequence in CHRFAM7A, which is present in many but not all humans. Maps of this region show that the two genes are in opposite orientation in the individual mainly represented in the public access human DNA sequence database (Build 36), suggesting that an inversion had occurred since the duplication. We have used fluorescent in situ hybridization to investigate this putative inversion. Analysis of interphase chromosomes in 12 individuals confirms the occurrence of an inversion and indicates that CHRFAM7A exists in both orientations with similar frequency. We showed that the 2 bp deletion polymorphism in exon 6 of CHRFAM7A is in strong linkage disequilibrium with the inversion polymorphism (r(2)=0.82, CI 0.53-1.00, P=0.00003), which can therefore be used as a surrogate marker. Previous associations of endophenotypes of schizophrenia with the 2 bp deletion might therefore be due to the orientation of the duplicon containing CHRFAM7A. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | Brain Res. 2009 Sep 1291: 1-11 |
| PMID | 19631623 |
| Title | A 2-base pair deletion polymorphism in the partial duplication of the alpha7 nicotinic acetylcholine gene (CHRFAM7A) on chromosome 15q14 is associated with schizophrenia. |
| Abstract | Multiple genetic linkage studies support the hypothesis that the 15q13-14 chromosomal region contributes to the etiology of schizophrenia. Among the putative candidate genes in this area are the alpha7 nicotinic acetylcholine receptor gene (CHRNA7) and its partial duplication, CHRFAM7A. A large chromosomal segment including the CHRFAM7A gene locus, but not the CHRNA7 locus, is deleted in some individuals. The CHRFAM7A gene contains a polymorphism consisting of a 2 base pair (2 bp) deletion at position 497-498 bp of exon 6. We employed PCR-based methods to quantify the copy number of CHRFAM7A and the presence of the 2 bp polymorphism in a large, multi-ethnic population. The 2 bp polymorphism was associated with schizophrenia in African Americans (genotype p=0.005, allele p=0.015), and in Caucasians (genotype p=0.015, allele p=0.009). We conclude that the presence of the 2 bp polymorphism at the CHRFAM7A locus may have a functional significance in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | Int. J. Neuropsychopharmacol. 2009 Mar 12: 267-73 |
| PMID | 19149910 |
| Title | CHRFAM7A copy number and 2-bp deletion polymorphisms and antisaccade performance. |
| Abstract | Chromosome 15q13-q14 harbours the gene for the alpha7 nicotinic acetylcholine receptor subunit (CHRNA7) and a related gene (CHRFAM7A) which arises from a partly duplicated portion of CHRNA7. Recent evidence suggests that CHRFAM7A is a locus with a possible role in schizophrenia and cognitive functioning. We studied an antisaccade task as a fronto-parietal measure of executive function that reflects risk for schizophrenia. Association of CHRFAM7A genotype with antisaccade performance was assessed in 103 healthy Caucasian individuals. No significant associations of 2-bp deletion or CHRFAM7A copy number with antisaccade performance parameters were observed. The failure to observe an association between antisaccade performance and polymorphisms in CHRFAM7A gene is consistent with specificity of the gene effects on hippocampal and memory functions as previously demonstrated. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 8 | J Neural Transm (Vienna) 2009 Feb 116: 213-20 |
| PMID | 19082523 |
| Title | Differentiating nicotine- versus schizophrenia-associated decreases of the alpha7 nicotinic acetylcholine receptor transcript, CHRFAM7A, in peripheral blood lymphocytes. |
| Abstract | Nicotine addiction is prevalent in individuals with schizophrenia. Nicotine activation of nicotinic receptors (nAChRs) is time- and dose-dependent, but gene expression analyses often rely on qualitative self- or family-reported measures of smoking. We sought lymphocyte surrogates for cerebral alpha7-nAChR activity and tested if receptor transcription correlated with concurrently measured serum biomarkers for smoking [cotinine, C-reactive protein (CRP)]. PCR surveys to detect lymphocytic alpha7-related isoforms identified CHRFAM7A as the only consistently amplifiable transcript. In 20 smoking-matched people (n = 10 schizophrenia, n = 10 controls), we found significantly lower CHRFAM7A in cotinine and self-reported smokers versus nonsmokers (p |
| SCZ Keywords | schizophrenia, schizophrenic |
| 9 | Biochem. Pharmacol. 2011 Oct 82: 904-14 |
| PMID | 21718690 |
| Title | The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of ?7*nAChR function. |
| Abstract | The human ?7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a candidate gene for schizophrenia and an important drug target for cognitive deficits in the disorder. Activation of the ?7*nAChR, results in opening of the channel and entry of mono- and divalent cations, including Ca(2+), that presynaptically participates to neurotransmitter release and postsynaptically to down-stream changes in gene expression. schizophrenic patients have low levels of ?7*nAChR, as measured by binding of the ligand [(125)I]-?-bungarotoxin (I-BTX). The structure of the gene, CHRNA7, is complex. During evolution, CHRNA7 was partially duplicated as a chimeric gene (CHRFAM7A), which is expressed in the human brain and elsewhere in the body. The association between a 2bp deletion in CHRFAM7A and schizophrenia suggested that this duplicate gene might contribute to cognitive impairment. To examine the putative contribution of CHRFAM7A on receptor function, co-expression of ?7 and the duplicate genes was carried out in cell lines and Xenopus oocytes. Expression of the duplicate alone yielded protein expression but no functional receptor and co-expression with ?7 caused a significant reduction of the amplitude of the ACh-evoked currents. Reduced current amplitude was not correlated with a reduction of I-BTX binding, suggesting the presence of non-functional (ACh-silent) receptors. This hypothesis is supported by a larger increase of the ACh-evoked current by the allosteric modulator 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596) in cells expressing the duplicate than in the control. These results suggest that CHRFAM7A acts as a dominant negative modulator of CHRNA7 function and is critical for receptor regulation in humans. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 10 | Biochem. Pharmacol. 2011 Oct 82: 904-14 |
| PMID | 21718690 |
| Title | The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of ?7*nAChR function. |
| Abstract | The human ?7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is a candidate gene for schizophrenia and an important drug target for cognitive deficits in the disorder. Activation of the ?7*nAChR, results in opening of the channel and entry of mono- and divalent cations, including Ca(2+), that presynaptically participates to neurotransmitter release and postsynaptically to down-stream changes in gene expression. schizophrenic patients have low levels of ?7*nAChR, as measured by binding of the ligand [(125)I]-?-bungarotoxin (I-BTX). The structure of the gene, CHRNA7, is complex. During evolution, CHRNA7 was partially duplicated as a chimeric gene (CHRFAM7A), which is expressed in the human brain and elsewhere in the body. The association between a 2bp deletion in CHRFAM7A and schizophrenia suggested that this duplicate gene might contribute to cognitive impairment. To examine the putative contribution of CHRFAM7A on receptor function, co-expression of ?7 and the duplicate genes was carried out in cell lines and Xenopus oocytes. Expression of the duplicate alone yielded protein expression but no functional receptor and co-expression with ?7 caused a significant reduction of the amplitude of the ACh-evoked currents. Reduced current amplitude was not correlated with a reduction of I-BTX binding, suggesting the presence of non-functional (ACh-silent) receptors. This hypothesis is supported by a larger increase of the ACh-evoked current by the allosteric modulator 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596) in cells expressing the duplicate than in the control. These results suggest that CHRFAM7A acts as a dominant negative modulator of CHRNA7 function and is critical for receptor regulation in humans. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 11 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2013 Dec 162B: 825-31 |
| PMID | 23894120 |
| Title | Microduplication of 15q13.3 and Xq21.31 in a family with Tourette syndrome and comorbidities. |
| Abstract | Tourette syndrome (TS) is a childhood onset neurodevelopmental disorder. Although it is widely accepted that genetic factors play a significant role in TS pathogenesis the etiology of this disorder is largely unknown. Identification of rare copy number variations (CNVs) as susceptibility factors in several neuropsychiatric disorders such as attention deficit-hyperactivity disorder (ADHD), autism and schizophrenia, suggests involvement of these rare structural changes also in TS etiology. In a male patient with TS, ADHD, and OCD (obsessive compulsive disorder) we identified two microduplications (at 15q13.3 and Xq21.31) inherited from a mother with subclinical ADHD. The 15q duplication included the CHRNA7 gene; while two genes, PABPC5 and PCDH11X, were within the Xq duplication. The Xq21.31 duplication was present in three brothers with TS including the proband, but not in an unaffected brother, whereas the 15q duplication was present only in the proband and his mother. The structural variations observed in this family may contribute to the observed symptoms, but further studies are necessary to investigate the possible involvement of the described variations in the TS etiology. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 12 | J. Biol. Chem. 2014 Sep 289: 26451-63 |
| PMID | 25056953 |
| Title | The duplicated ?7 subunits assemble and form functional nicotinic receptors with the full-length ?7. |
| Abstract | The ?7 nicotinic acetylcholine receptor gene (CHRNA7) is linked to schizophrenia. A partial duplication of CHRNA7 (CHRFAM7A) is found in humans on 15q13-14. Exon 6 of CHRFAM7A harbors a 2-bp deletion polymorphism, CHRFAM7A?2bp, which is also associated with schizophrenia. To understand the effects of the duplicated subunits on ?7 receptors, we fused ?7, dup?7, and dup??7 subunits with various fluorescent proteins. The duplicated subunits co-localized with full-length ?7 subunits in mouse neuroblastoma cells (Neuro2a) as well as rat hippocampal neurons. We investigated the interaction between the duplicated subunits and full-length ?7 by measuring Förster resonance energy transfer using donor recovery after photobleaching and fluorescence lifetime imaging microscopy. The results revealed that the duplicated proteins co-assemble with ?7. In electrophysiological studies, Leu at the 9'-position in the M2 membrane-spanning segment was replaced with Cys in dup?7 or dup??7, and constructs were co-transfected with full-length ?7 in Neuro2a cells. Exposure to ethylammonium methanethiosulfonate inhibited acetylcholine-induced currents, showing that the assembled functional nicotinic acetylcholine receptors (nAChRs) included the duplicated subunit. Incorporation of dup?7 and dup??7 subunits modestly changes the sensitivity of receptors to choline and varenicline. Thus, the duplicated proteins are assembled and transported to the cell membrane together with full-length ?7 subunits and alter the function of the nAChRs. The characterization of dup?7 and dup??7 as well as their influence on ?7 nAChRs may help explain the pathophysiology of schizophrenia and may suggest therapeutic strategies. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 13 | PLoS ONE 2015 -1 10: e0125116 |
| PMID | 25906356 |
| Title | Pharmacological Characterisation of Nicotinic Acetylcholine Receptors Expressed in Human iPSC-Derived Neurons. |
| Abstract | Neurons derived from human induced pluripotent stem cells (iPSCs) represent a potentially valuable tool for the characterisation of neuronal receptors and ion channels. Previous studies on iPSC-derived neuronal cells have reported the functional characterisation of a variety of receptors and ion channels, including glutamate receptors, ?-aminobutyric acid (GABA) receptors and several voltage-gated ion channels. In the present study we have examined the expression and functional properties of nicotinic acetylcholine receptors (nAChRs) in human iPSC-derived neurons. Gene expression analysis indicated the presence of transcripts encoding several nAChR subunits, with highest levels detected for ?3-?7, ?1, ?2 and ?4 subunits (encoded by CHRNA3-CHRNA7, CHRNB1, CHRNB2 and CHRNB4 genes). In addition, similarly high transcript levels were detected for the truncated dup?7 subunit transcript, encoded by the partially duplicated gene CHRFAM7A, which has been associated with psychiatric disorders such as schizophrenia. The functional properties of these nAChRs have been examined by calcium fluorescence and by patch-clamp recordings. The data obtained suggest that the majority of functional nAChRs expressed in these cells have pharmacological properties typical of ?7 receptors. Large responses were induced by a selective ?7 agonist (compound B), in the presence of the ?7-selective positive allosteric modulator (PAM) PNU-120596, which were blocked by the ?7-selective antagonist methyllycaconitine (MLA). In addition, a small proportion of the neurons express nAChRs with properties typical of heteromeric (non-?7 containing) nAChR subtypes. These cells therefore represent a great tool to advance our understanding of the properties of native human nAChRs, ?7 in particular. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 14 | Epilepsy Res. 2015 Nov 117: 70-3 |
| PMID | 26421493 |
| Title | Evaluation of multiple putative risk alleles within the 15q13.3 region for genetic generalized epilepsy. |
| Abstract | The chromosome 15q13.3 region has been implicated in epilepsy, intellectual disability and neuropsychiatric disorders, especially schizophrenia. Deficiency of the acetylcholine receptor gene CHRNA7 and the partial duplication, CHRFAM7A, may contribute to these phenotypes and we sought to comprehensively analyze these genes in genetic generalized epilepsy. We analyzed using DHPLC, Sanger sequencing and long range PCR, 174 probands with genetic generalized epilepsy with or without intellectual disability or psychosis, including 8 with the recurrent 15q13.3 microdeletion. We searched CHRNA7 and CHRFAM7A for single sequence variants, small copy number variants, and the common 2-bp deletion in CHRFAM7A. We identified two novel and one reported missense variants. The common 2-bp deletion was not enriched in patients compared to controls. Our data suggest that missense mutations in CHRNA7 contribute to complex inheritance in genetic generalized epilepsy in a similar fashion to the 15q13.3 microdeletion. They do not support a pathogenic role for the common 2-bp CHRFAM7A deletion. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 15 | Am J Psychiatry 2015 Nov 172: 1122-30 |
| PMID | 26206074 |
| Title | CHRNA7 and CHRFAM7A mRNAs: co-localized and their expression levels altered in the postmortem dorsolateral prefrontal cortex in major psychiatric disorders. |
| Abstract | CHRNA7, coding ?-7 nicotinic acetylcholine receptor (?7 nAChR), is involved in cognition through interneuron modulation of dopamine and glutamate signaling. CHRNA7 and its partially duplicated chimeric gene CHRFAM7A have been implicated in schizophrenia through linkage and association studies. Expression of CHRNA7 and CHRFAM7A mRNA was measured in the postmortem prefrontal cortex in more than 700 subjects, including patients with schizophrenia, bipolar disorder, major depression, and normal comparison subjects. The effects of antipsychotics and nicotine, as well as associations of CHRNA7 SNPs with gene expression, were explored. Fluorescent in-situ hybridization was used to examine coexpression of both transcripts in the human cortex. CHRFAM7A expression and CHRFAM7A/CHRNA7 ratios were higher in fetal compared with postnatal life, whereas CHRNA7 expression was relatively stable. CHRFAM7A expression was significantly elevated in all diagnostic groups, while CHRNA7 expression was reduced in the schizophrenia group and increased in the major depression group compared with the comparison group. CHRFAM7A/CHRNA7 ratios were significantly increased in the schizophrenia and bipolar disorder groups compared with the comparison group. There was no effect of nicotine or antipsychotics and no association of SNPs in CHRNA7 with expression. CHRNA7 and CHRFAM7A mRNAs were expressed in the same neuronal nuclei of the human neocortex. These data show preferential fetal CHRFAM7A expression in the human prefrontal cortex and suggest abnormalities in the CHRFAM7A/CHRNA7 ratios in schizophrenia and bipolar disorder, due mainly to overexpression of CHRFAM7A. Given that these transcripts are coexpressed in a subset of human cortical neurons and can interact to alter function of nAChRs, these results support the concept of aberrant function of nAChRs in mental illness. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 16 | Neuropharmacology 2015 Sep 96: 274-88 |
| PMID | 25701707 |
| Title | The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function. |
| Abstract | The human ?7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is ubiquitously expressed in both the central nervous system and in the periphery. CHRNA7 is genetically linked to multiple disorders with cognitive deficits, including schizophrenia, bipolar disorder, ADHD, epilepsy, Alzheimer's disease, and Rett syndrome. The regulation of CHRNA7 is complex; more than a dozen mechanisms are known, one of which is a partial duplication of the parent gene. Exons 5-10 of CHRNA7 on chromosome 15 were duplicated and inserted 1.6 Mb upstream of CHRNA7, interrupting an earlier partial duplication of two other genes. The chimeric CHRFAM7A gene product, dup?7, assembles with ?7 subunits, resulting in a dominant negative regulation of function. The duplication is human specific, occurring neither in primates nor in rodents. The duplicated ?7 sequence in exons 5-10 of CHRFAM7A is almost identical to CHRNA7, and thus is not completely queried in high throughput genetic studies (GWAS). Further, pre-clinical animal models of the ?7nAChR utilized in drug development research do not have CHRFAM7A (dup?7) and cannot fully model human drug responses. The wide expression of CHRNA7, its multiple functions and modes of regulation present challenges for study of this gene in disease. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 17 | FASEB J. 2015 Jun 29: 2292-302 |
| PMID | 25681457 |
| Title | CHRFAM7A: a human-specific ?7-nicotinic acetylcholine receptor gene shows differential responsiveness of human intestinal epithelial cells to LPS. |
| Abstract | The human genome contains a unique, distinct, and human-specific ?7-nicotinic acetylcholine receptor (?7nAChR) gene [CHRNA7 (gene-encoding ?7-nicotinic acetylcholine receptor)] called CHRFAM7A (gene-encoding dup-?7-nicotinic acetylcholine receptor) on a locus of chromosome 15 associated with mental illness, including schizophrenia. Located 5' upstream from the "wild-type" CHRNA7 gene that is found in other vertebrates, we demonstrate CHRFAM7A expression in a broad range of epithelial cells and sequenced the CHRFAM7A transcript found in normal human fetal small intestine epithelial (FHs) cells to prove its identity. We then compared its expression to CHRNA7 in 11 gut epithelial cell lines, showed that there is a differential response to LPS when compared to CHRNA7, and characterized the CHRFAM7A promoter. We report that both CHRFAM7A and CHRNA7 gene expression are widely distributed in human epithelial cell lines but that the levels of CHRFAM7A gene expression vary up to 5000-fold between different gut epithelial cells. A 3-hour treatment of epithelial cells with 100 ng/ml LPS increased CHRFAM7A gene expression by almost 1000-fold but had little effect on CHRNA7 gene expression. Mapping the regulatory elements responsible for CHRFAM7A gene expression identifies a 1 kb sequence in the UTR of the CHRFAM7A gene that is modulated by LPS. Taken together, these data establish the presence, identity, and differential regulation of the human-specific CHRFAM7A gene in human gut epithelial cells. In light of the fact that CHRFAM7A expression is reported to modulate ligand binding to, and alter the activity of, the wild-type ?7nAChR ligand-gated pentameric ion channel, the findings point to the existence of a species-specific ?7nAChR response that might regulate gut epithelial function in a human-specific fashion. |
| SCZ Keywords | schizophrenia, schizophrenic |