The discovery of genomic rearrangements, known as copy number variations (CNVs), is relatively new; their contribution to genetic heterogeneity and their impact on human diseases is still largely unknown. CNVs within the human 15q13.3 region have been associated with neuropsychiatric and neurodevelopmental disorders such as schizophrenia, autism spectrum disorders (ASD), intellectual disability, and epilepsy. Several recent studies suggest that, within this chromosomic region, the gene CHRNA7, encoding for the human alfa7 subunit of the nicotinic acetylcholine receptor, plays a major role in the observed pathological phenotypes. Consistently, patients carrying deletions or duplications of CHRNA7 present symptoms comparable to patients with a larger 1.5. Mb deletion of the 15q13.3 region. The penetrance of CHRNA7 CNVs is variable, and the exact pathogenic mechanisms are currently being elucidated.In this chapter, we have critically reviewed all up-to-date studies regarding the functional outcomes of CNVs involving the alpha7-nicontinic receptor (α7nAChR), highlighting the advantages and disadvantages of the methodologies and models utilized. We have described the structure, functionality, and physiological role of the α7nAChR, analyzing the mechanisms that determine the occurrence of CNVs and the clinical features of patients carrying CNRNA7 CNVs. We have examined and compared the mice models used to study the role of these CNVs and the new human model of induced pluripotent stem cells, which is proving very useful in clarifying the clinical and phenotypic features pertaining specifically to humans.
Ferrari, D., D'Anzi, A., Casamassa, A., Bernardini, L., Tata, A., Vescovi, A., et al. (2022). Functional outcomes of copy number variations of Chrna7 gene: Current knowledge and new insight from induced pluripotent stem cells studies. In A. Birbrair (a cura di), Novel Concepts in iPSC Disease Modeling (pp. 269-306). Academic Press [10.1016/B978-0-12-823882-0.00012-6].
Functional outcomes of copy number variations of Chrna7 gene: Current knowledge and new insight from induced pluripotent stem cells studies
Ferrari D.Co-primo
;Vescovi A. L.
;
2022
Abstract
The discovery of genomic rearrangements, known as copy number variations (CNVs), is relatively new; their contribution to genetic heterogeneity and their impact on human diseases is still largely unknown. CNVs within the human 15q13.3 region have been associated with neuropsychiatric and neurodevelopmental disorders such as schizophrenia, autism spectrum disorders (ASD), intellectual disability, and epilepsy. Several recent studies suggest that, within this chromosomic region, the gene CHRNA7, encoding for the human alfa7 subunit of the nicotinic acetylcholine receptor, plays a major role in the observed pathological phenotypes. Consistently, patients carrying deletions or duplications of CHRNA7 present symptoms comparable to patients with a larger 1.5. Mb deletion of the 15q13.3 region. The penetrance of CHRNA7 CNVs is variable, and the exact pathogenic mechanisms are currently being elucidated.In this chapter, we have critically reviewed all up-to-date studies regarding the functional outcomes of CNVs involving the alpha7-nicontinic receptor (α7nAChR), highlighting the advantages and disadvantages of the methodologies and models utilized. We have described the structure, functionality, and physiological role of the α7nAChR, analyzing the mechanisms that determine the occurrence of CNVs and the clinical features of patients carrying CNRNA7 CNVs. We have examined and compared the mice models used to study the role of these CNVs and the new human model of induced pluripotent stem cells, which is proving very useful in clarifying the clinical and phenotypic features pertaining specifically to humans.
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