TY - JOUR
T1 - Copy number variants (CNVs)
T2 - A powerful tool for iPSC-based modelling of ASD
AU - Drakulic, Danijela
AU - Djurovic, Srdjan
AU - Syed, Yasir Ahmed
AU - Trattaro, Sebastiano
AU - Caporale, Nicolò
AU - Falk, Anna
AU - Ofir, Rivka
AU - Heine, Vivi M.
AU - Chawner, Samuel J.R.A.
AU - Rodriguez-Moreno, Antonio
AU - Van Den Bree, Marianne B.M.
AU - Testa, Giuseppe
AU - Petrakis, Spyros
AU - Harwood, Adrian J.
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - Autism spectrum disorders (ASD)
KW - Copy number variants (CNVs)
KW - Human iPSCs
KW - Neurodevelopmental disorders (NDD)
UR - http://www.scopus.com/inward/record.url?scp=85085908802&partnerID=8YFLogxK
U2 - 10.1186/s13229-020-00343-4
DO - 10.1186/s13229-020-00343-4
M3 - Review article
C2 - 32487215
AN - SCOPUS:85085908802
SN - 2040-2392
VL - 11
JO - Molecular Autism
JF - Molecular Autism
IS - 1
M1 - 42
ER -