ArticleAmerican journal of human genetics2017
Functional Consequences of CHRNA7 Copy-Number Alterations in Induced Pluripotent Stem Cells and Neural Progenitor Cells.
Article in American journal of human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Estimation on risk of spontaneous abortions by genomic disorders from a meta-analysis of microarray results on large case series of pregnancy losses.Molecular genetics & genomic medicine · 2023Pooled it
- Rare Copy Number Variants Reveal Critical Cell Types and Periods of Brain Development in Neurodevelopmental Disorders.Biological psychiatry global open science · 2025Article
- Modeling antisense oligonucleotide therapy in MECP2 duplication syndrome human iPSC-derived neurons reveals gene expression programs responsive to MeCP2 levels.Human molecular genetics · 2024Article
- Modeling common and rare genetic risk factors of neuropsychiatric disorders in human induced pluripotent stem cells.Schizophrenia research · 2024Review
- Decoding the genetic landscape of autism: A comprehensive review.World journal of clinical pediatrics · 2024Article
- Impaired OTUD7A-dependent Ankyrin regulation mediates neuronal dysfunction in mouse and human models of the 15q13.3 microdeletion syndrome.Molecular psychiatry · 2023Article
- The OTUD7A-Ankyrin pathway: a newly identified disease mechanism for the 15q13.3 microdeletion disorder.Molecular psychiatry · 2023Article
- Duplication Versus Deletion Through the Lens of 15q13.3: Clinical and Research Implications of Studying Copy Number Variants Associated with Neuropsychiatric Disorders in Induced Pluripotent Stem Cell-Derived Neurons.Stem cell reviews and reports · 2023Review
- Nexus between genome-wide copy number variations and autism spectrum disorder in Northeast Han Chinese population.BMC psychiatry · 2023Article
- Construction of copy number variation landscape and characterization of associated genes in a Bangladeshi cohort of neurodevelopmental disorders.Frontiers in genetics · 2023Article
- Review
- Altered gene expression profiles impair the nervous system development in individuals with 15q13.3 microdeletion.Scientific reports · 2022Article
- Genes To Mental Health (G2MH): A Framework to Map the Combined Effects of Rare and Common Variants on Dimensions of Cognition and Psychopathology.The American journal of psychiatry · 2022Review
- Deepening the understanding of CNVs on chromosome 15q11-13 by using hiPSCs: An overview.Frontiers in cell and developmental biology · 2022Review
- Screening for Copy Number Variations of the 15q13.3 Hotspot inCurrent issues in molecular biology · 2021Article
- Altered neuronal physiology, development, and function associated with a common chromosome 15 duplication involving CHRNA7.BMC biology · 2021Article
- Article
- Network Effects of the 15q13.3 Microdeletion on the Transcriptome and Epigenome in Human-Induced Neurons.Biological psychiatry · 2021Article
- Mind the translational gap: using iPS cell models to bridge from genetic discoveries to perturbed pathways and therapeutic targets.Molecular autism · 2021Review
- Multiple Roles for Cholinergic Signaling from the Perspective of Stem Cell Function.International journal of molecular sciences · 2021Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Copy-number variants (CNVs) of chromosome 15q13.3 manifest clinically as neuropsychiatric disorders with variable expressivity. CHRNA7, encoding for the α7 nicotinic acetylcholine receptor (nAChR), has been suggested as a candidate gene for the phenotypes observed. Here, we used induced pluripotent stem cells (iPSCs) and neural progenitor cells (NPCs) derived from individuals with heterozygous 15q13.3 deletions and heterozygous 15q13.3 duplications to investigate the CHRNA7-dependent molecular consequences of the respective CNVs. Unexpectedly, both deletions and duplications lead to decreased α7 nAChR-associated calcium flux. For deletions, this decrease in α7 nAChR-dependent calcium flux is expected due to haploinsufficiency of CHRNA7. For duplications, we found that increased expression of CHRNA7 mRNA is associated with higher expression of nAChR-specific and resident ER chaperones, indicating increased ER stress. This is likely a consequence of inefficient chaperoning and accumulation of α7 subunits in the ER, as opposed to being incorporated into functional α7 nAChRs at the cell membrane. Here, we showed that α7 nAChR-dependent calcium signal cascades are downregulated in both 15q13.3 deletion and duplication NPCs. While it may seem surprising that genomic changes in opposite direction have consequences on downstream pathways that are in similar direction, it aligns with clinical data, which suggest that both individuals with deletions and duplications of 15q13.3 manifest neuropsychiatric disease and cognitive deficits.
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