Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jan 6:10:1107881.
doi: 10.3389/fcell.2022.1107881. eCollection 2022.

Deepening the understanding of CNVs on chromosome 15q11-13 by using hiPSCs: An overview

Angela Maria Giada Giovenale  1   2 , Giorgia Ruotolo  1   2 , Amata Amy Soriano  1 , Elisa Maria Turco  1 , Giovannina Rotundo  1 , Alessia Casamassa  1 , Angela D'Anzi  1 , Angelo Luigi Vescovi  1   2 , Jessica Rosati  1
Affiliations
Review

Deepening the understanding of CNVs on chromosome 15q11-13 by using hiPSCs: An overview

Angela Maria Giada Giovenale et al. Front Cell Dev Biol. .

Erratum in

Abstract

The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is widely expressed in the central and peripheral nervous systems. This receptor is implicated in both brain development and adult neurogenesis thanks to its ability to mediate acetylcholine stimulus (Ach). Copy number variations (CNVs) of CHRNA7 gene have been identified in humans and are genetically linked to cognitive impairments associated with multiple disorders, including schizophrenia, bipolar disorder, epilepsy, Alzheimer's disease, and others. Currently, α7 receptor analysis has been commonly performed in animal models due to the impossibility of direct investigation of the living human brain. But the use of model systems has shown that there are very large differences between humans and mice when researchers must study the CNVs and, in particular, the CNV of chromosome 15q13.3 where the CHRNA7 gene is present. In fact, human beings present genomic alterations as well as the presence of genes of recent origin that are not present in other model systems as well as they show a very heterogeneous symptomatology that is associated with both their genetic background and the environment where they live. To date, the induced pluripotent stem cells, obtained from patients carrying CNV in CHRNA7 gene, are a good in vitro model for studying the association of the α7 receptor to human diseases. In this review, we will outline the current state of hiPSCs technology applications in neurological diseases caused by CNVs in CHRNA7 gene. Furthermore, we will discuss some weaknesses that emerge from the overall analysis of the published articles.

Keywords: 15q11-13; CHRNA7; CNV; copy number variation; neurodevelopmental disorders; neuropsychiatric disorders; nicotinic acetylcholine receptor.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic representation of the CHRNA7 locus. (A) Orthologus locus in mus musculus, at the 7qC chromosome. (B) Different genetic profiles of the human Chromosome 15q13.3, without duplication, with the chimeric gene and with the 2bp mutation.
FIGURE 2
FIGURE 2
Reprogramming and differentiation of hiPSCs. Different adult somatic cells can be reprogrammed in induced Pluripotent Stem Cells. Once hiPSCs have been obtained, they can be used to generate all types of terminally differentiated cells.
FIGURE 3
FIGURE 3
Chromosome 15q13.3 and hiPSCs derived from individuals with CNV. Graphic representation of chromosomal region 15q13.3 showing BreakPoint regions BP3, BP4, and BP5 and the extensions the microdeletions and microduplications present in the hiPSCs in the published studies.
FIGURE 4
FIGURE 4
An insight into molecular effects of CNV 15q13.3. Cells carrying CNV duplications show decreased calcium flux associated with the α7 receptor, downregulation of JAK2-PI3K pathway, decreased assembly and trafficking of nAchRs, and ER stress. Cells carrying CNV deletions exhibit decreased α7nAchRs calcium flux and downregulation of JAK2-PI3K pathway.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Araud T., Graw S., Berger R., Lee M., Neveu E., Bertrand D., et al. (2011). The chimeric gene CHRFAM7A, a partial duplication of the CHRNA7 gene, is a dominant negative regulator of α7*nAChR function Biochem. Pharmacol. 82 (8), 904–914. 10.1016/j.bcp.2011.06.018 - DOI - PMC - PubMed
    1. Bacchelli E., Battaglia A., Cameli C., Lomartire S., Tancredi R., Thomson S., et al. (2015). Analysis of CHRNA7 rare variants in autism spectrum disorder susceptibility. Am. J. Med. Genet. A 167A (4), 715–723. 10.1002/ajmg.a.36847 - DOI - PubMed
    1. Beal J. C. (2014). Case report: Neuronal migration disorder associated with chromosome 15q13.3 duplication in a boy with autism and seizures. J. Child. Neurol29(12) 29, NP186–8. 10.1177/0883073813510356 - DOI - PubMed
    1. Ben-Shachar S., Lanpher B., German J. R., Qasaymeh M., Potocki L., Nagamani S. C. S., et al. (2009). Microdeletion 15q13.3: A locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders. J. Med. Genet. 46 (6), 382–388. 10.1136/jmg.2008.064378 - DOI - PMC - PubMed
    1. Brown M. E., Rondon E., Rajesh D., Mack A., Lewis R., Feng X., et al. (2010). Derivation of induced pluripotent stem cells from human peripheral blood T lymphocytes. PLoS One 5 (6), e11373. 10.1371/journal.pone.0011373 - DOI - PMC - PubMed

LinkOut - more resources