Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASD
Abstract Patients diagnosed with chromosome microdeletions or duplications, known as copy number variants (CNVs), present a unique opportunity to investigate the relationship between patient genotype and cell phenotype. CNVs have high genetic penetrance and give a good correlation between gene locus...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Molecular Autism |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13229-020-00343-4 |
| _version_ | 1818020461116653568 |
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| author | Danijela Drakulic Srdjan Djurovic Yasir Ahmed Syed Sebastiano Trattaro Nicolò Caporale Anna Falk Rivka Ofir Vivi M. Heine Samuel J. R. A. Chawner Antonio Rodriguez-Moreno Marianne B. M. van den Bree Giuseppe Testa Spyros Petrakis Adrian J. Harwood |
| author_facet | Danijela Drakulic Srdjan Djurovic Yasir Ahmed Syed Sebastiano Trattaro Nicolò Caporale Anna Falk Rivka Ofir Vivi M. Heine Samuel J. R. A. Chawner Antonio Rodriguez-Moreno Marianne B. M. van den Bree Giuseppe Testa Spyros Petrakis Adrian J. Harwood |
| author_sort | Danijela Drakulic |
| collection | DOAJ |
| description | Abstract Patients diagnosed with chromosome microdeletions or duplications, known as copy number variants (CNVs), present a unique opportunity to investigate the relationship between patient genotype and cell phenotype. CNVs have high genetic penetrance and give a good correlation between gene locus and patient clinical phenotype. This is especially effective for the study of patients with neurodevelopmental disorders (NDD), including those falling within the autism spectrum disorders (ASD). A key question is whether this correlation between genetics and clinical presentation at the level of the patient can be translated to the cell phenotypes arising from the neurodevelopment of patient induced pluripotent stem cells (iPSCs). Here, we examine how iPSCs derived from ASD patients with an associated CNV inform our understanding of the genetic and biological mechanisms underlying the aetiology of ASD. We consider selection of genetically characterised patient iPSCs; use of appropriate control lines; aspects of human neurocellular biology that can capture in vitro the patient clinical phenotype; and current limitations of patient iPSC-based studies. Finally, we consider how future research may be enhanced to maximise the utility of CNV patients for research of pathological mechanisms or therapeutic targets. |
| first_indexed | 2024-04-14T08:05:37Z |
| format | Article |
| id | doaj.art-d4e8450a48824f23b625b697df32b39b |
| institution | Directory Open Access Journal |
| issn | 2040-2392 |
| language | English |
| last_indexed | 2024-04-14T08:05:37Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Autism |
| spelling | doaj.art-d4e8450a48824f23b625b697df32b39b2022-12-22T02:04:46ZengBMCMolecular Autism2040-23922020-06-0111111810.1186/s13229-020-00343-4Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASDDanijela Drakulic0Srdjan Djurovic1Yasir Ahmed Syed2Sebastiano Trattaro3Nicolò Caporale4Anna Falk5Rivka Ofir6Vivi M. Heine7Samuel J. R. A. Chawner8Antonio Rodriguez-Moreno9Marianne B. M. van den Bree10Giuseppe Testa11Spyros Petrakis12Adrian J. Harwood13Institute of Molecular Genetics and Genetic Engineering, University of BelgradeDepartment of Medical Genetics, Oslo University HospitalNeuroscience & Mental Health Research Institute, Cardiff UniversityLaboratory of Stem Cell Epigenetics, IEO, European Institute of Oncology, IRCCSLaboratory of Stem Cell Epigenetics, IEO, European Institute of Oncology, IRCCSDepartment of Neuroscience, Karolinska InstitutetBGU-iPSC Core Facility, The Regenerative Medicine & Stem Cell (RMSC) Research Center, Ben Gurion University of the NegevComplex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit AmsterdamNeuroscience & Mental Health Research Institute, Cardiff UniversityDepartment of Physiology, Anatomy and Cell Biology, University Pablo de OlavideNeuroscience & Mental Health Research Institute, Cardiff UniversityLaboratory of Stem Cell Epigenetics, IEO, European Institute of Oncology, IRCCSInstitute of Applied Biosciences/Centre for Research and Technology HellasNeuroscience & Mental Health Research Institute, Cardiff UniversityAbstract Patients diagnosed with chromosome microdeletions or duplications, known as copy number variants (CNVs), present a unique opportunity to investigate the relationship between patient genotype and cell phenotype. CNVs have high genetic penetrance and give a good correlation between gene locus and patient clinical phenotype. This is especially effective for the study of patients with neurodevelopmental disorders (NDD), including those falling within the autism spectrum disorders (ASD). A key question is whether this correlation between genetics and clinical presentation at the level of the patient can be translated to the cell phenotypes arising from the neurodevelopment of patient induced pluripotent stem cells (iPSCs). Here, we examine how iPSCs derived from ASD patients with an associated CNV inform our understanding of the genetic and biological mechanisms underlying the aetiology of ASD. We consider selection of genetically characterised patient iPSCs; use of appropriate control lines; aspects of human neurocellular biology that can capture in vitro the patient clinical phenotype; and current limitations of patient iPSC-based studies. Finally, we consider how future research may be enhanced to maximise the utility of CNV patients for research of pathological mechanisms or therapeutic targets.http://link.springer.com/article/10.1186/s13229-020-00343-4Human iPSCsCopy number variants (CNVs)Neurodevelopmental disorders (NDD)Autism spectrum disorders (ASD) |
| spellingShingle | Danijela Drakulic Srdjan Djurovic Yasir Ahmed Syed Sebastiano Trattaro Nicolò Caporale Anna Falk Rivka Ofir Vivi M. Heine Samuel J. R. A. Chawner Antonio Rodriguez-Moreno Marianne B. M. van den Bree Giuseppe Testa Spyros Petrakis Adrian J. Harwood Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASD Molecular Autism Human iPSCs Copy number variants (CNVs) Neurodevelopmental disorders (NDD) Autism spectrum disorders (ASD) |
| title | Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASD |
| title_full | Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASD |
| title_fullStr | Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASD |
| title_full_unstemmed | Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASD |
| title_short | Copy number variants (CNVs): a powerful tool for iPSC-based modelling of ASD |
| title_sort | copy number variants cnvs a powerful tool for ipsc based modelling of asd |
| topic | Human iPSCs Copy number variants (CNVs) Neurodevelopmental disorders (NDD) Autism spectrum disorders (ASD) |
| url | http://link.springer.com/article/10.1186/s13229-020-00343-4 |
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