The uniquely human α7-nAChR gene (CHRFAM7A) is evolved from the fusion of two partially duplicated genes, FAM7 and α7-nAChR gene (CHRNA7), and is inserted on same chromosome 15, 5' end of the CHRNA7 gene. Transcription of CHRFAM7A gene produces a 1256-bp open reading frame encoding dup-α7-nAChR, where a 27-aminoacid residues from FAM7 replaced the 146-aminoacid residues of the N-terminal extracellular ligand binding domain of α7-nAChR. In vitro, dup-α7-nAChR has been shown to form hetero-pentamer with α7-nAChR and dominant-negatively regulates the channel functions of α7-nAChR. However, the contribution of CHRFAM7A gene to the biology of α7-nAChR in the brain in vivo remains largely a matter of conjecture. CHRFAM7A transgenic mouse was created and differentially expressed proteins were profiled from the whole brain using iTRAQ-2D-LC-MS/MS proteomic technology. Proteins with a fold change of ≥1.2 or ≤0.83 and p < 0.05 were considered to be significant. Bioinformatics analysis showed that over-expression of the CHRFAM7A gene significantly modulated the proteins commonly involved in the signaling pathways of α7-nAChR-mediated neuropsychiatric disorders including Parkinson's disease, Alzheimer's disease, Huntington's disease, and alcoholism, suggesting that the CHRFAM7A gene contributes to the pathogenesis of neuropsychiatric disorders mostly likely through fine-tuning the functions of α7-nAChR in the brain.
Keywords: CHRFAM7A; CHRNA7; Human-specific gene; Neuropsychiatric disorders.
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