title: The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function.
abstract: 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. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'.
authors.affiliation: Department of Psychiatry, University of Colorado Denver, Aurora, CO 80045, USA. Electronic address: Melissa.Sinkus@ucdenver.edu.
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Sinkus
authors.affiliation: Department of Psychiatry, University of Colorado Denver, Aurora, CO 80045, USA. Electronic address: Sharon.Graw@ucdenver.edu.
authors.forename: Sharon
authors.initials: S
authors.lastname: Graw
authors.affiliation: Department of Psychiatry, University of Colorado Denver, Aurora, CO 80045, USA; Veterans Affairs Medical Research Center, Denver, CO 80262, USA. Electronic address: Robert.Freedman@ucdenver.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Freedman
authors.affiliation: Department of Psychiatry, University of Colorado Denver, Aurora, CO 80045, USA. Electronic address: Randy.Ross@ucdenver.edu.
authors.forename: Randal G
authors.initials: RG
authors.lastname: Ross
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: lester@caltech.edu.
authors.forename: Henry A
authors.initials: HA
authors.lastname: Lester
authors.affiliation: Department of Psychiatry, University of Colorado Denver, Aurora, CO 80045, USA; Veterans Affairs Medical Research Center, Denver, CO 80262, USA. Electronic address: Sherry.Leonard@ucdenver.edu.
authors.forename: Sherry
authors.initials: S
authors.lastname: Leonard
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002884:Chromosomes, Human, Pair 15; D003071:Cognition / Q000502:physiology; D005091:Exons; D020440:Gene Duplication; D005786:Gene Expression Regulation; D006801:Humans; D001523:Mental Disorders / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics* / Q000378:metabolism*
chemical_list: C579167:Chrna7 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: Alzheimer's; CHRFAM7A; CHRNA7; Gene duplication; Gene mutation; Nicotinic receptor; Schizophrenia