Linkage disequilibrium analysis of the CHRNA7 gene and its partially duplicated region in schizophrenia

Iwata, Yasuhide; Nakajima, Mizuho; Yamada, Kazuo; Nakamura, Kazuhiko; Sekine, Yoshimoto; Tsuchiya, Kenji J.; Sugihara, Genichi; Matsuzaki, Hideo; Suda, Shiro; Suzuki, Katsuaki; Takei, Nori; Mori, N. T.; Iwayama, Yoshimi; Takao, Hitomi; Yoshikawa, Takeo; Riley, Brien P.; Makoff, Andrew; Sham, Pak C.; Chen, Ronald; Collier, David

doi:10.1016/j.neures.2006.10.002

Cited by 18 publications

(13 citation statements)

References 49 publications

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“…Subsequent positive linkage to schizophrenia was found to other microsatellite markers near the CHRNA7 gene at 15q13.3 that are not in duplicated regions (Faraone et al, 2004; Freedman et al, 2001; Gejman et al, 2001; Kaufmann et al, 1998; Liu et al, 2001; Riley et al, 2000; Tsuang et al, 2001)(Table 2). Other groups did not find linkage to this region using similar methodology (Curtis et al, 1999; Iwata et al, 2007; Neves-Pereira et al, 1998). An association study of 14 candidate genes with schizophrenia in a large European cohort failed to find significant association to any of these genes, highlighting the importance of heterogeneity in the genetics of mental disorders (Sanders et al, 2008).…”

Section: 0 Genetics Of Chrna7 and Chrfam7a In Mental Illnessesmentioning

confidence: 85%

The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function

et al. 2015

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The human α7 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, dupα7, assembles with α7 subunits, resulting in a dominant negative regulation of function. The duplication is human specific, occurring neither in primates nor in rodents. The duplicated α7 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 α7nAChR utilized in drug development research do not have CHRFAM7A (dupα7) 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.

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Section: 0 Genetics Of Chrna7 and Chrfam7a In Mental Illnessesmentioning

confidence: 85%

The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function

et al. 2015

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“…Additionally, in two separate studies in patients with AD in Northern Ireland, SNP rs6494233 was significantly associated with delusional symptoms (Carson et al, 2008a), whereas SNPs rs1514246, rs2337506, and rs8027814 were significantly associated with a reduced risk of AD (Carson et al, 2008b). There have been a number of other genetic association studies between CHRNA7 SNPs and various disease states, which all Therapeutic Potential of a7 nAChRs failed to show any significant association (Iwata et al, 2007;Joo et al, 2010;Neri et al, 2012;Cabranes et al, 2013).…”

Section: A the Chrna7 Gene And Its Variantsmentioning

confidence: 99%

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

et al. 2015

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“…To this end, studies of the CHRFAM7A locus on human chromosome 15 have historically focused on its association with schizophrenia (29,(57)(58)(59)(60)(65)(66)(67)(68)(69)(70), a prototypically human-specific disease, and not inflammation or epithelial biology. Yet, interestingly, schizophrenia is associated with changed risk for colon cancer and irritable bowel syndromes (71)(72)(73)(74)(75)(76)(77) and interestingly, a 2 bp mutation in CHRFAM7A.…”

Section: Stdmentioning

confidence: 99%

CHRFAM7A: a human‐specific α7‐nicotinic acetylcholine receptor gene shows differential responsiveness of human intestinal epithelial cells to LPS

et al. 2015

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The human genome contains a unique, distinct, and human-specific a7-nicotinic acetylcholine receptor (a7nAChR) gene [CHRNA7 (gene-encoding a7-nicotinic acetylcholine receptor)] called CHRFAM7A (gene-encoding dup-a7-nicotinic acetylcholine receptor) on a locus of chromosome 15 associated with mental illness, including schizophrenia. Located 59 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

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Linkage disequilibrium analysis of the CHRNA7 gene and its partially duplicated region in schizophrenia

Cited by 18 publications

References 49 publications

The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function

The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

CHRFAM7A: a human‐specific α7‐nicotinic acetylcholine receptor gene shows differential responsiveness of human intestinal epithelial cells to LPS

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