Application of CRISPR Tools for Variant Interpretation and Disease Modeling in Inherited Retinal Dystrophies
Open Access
- 27 April 2020
- Vol. 11 (5), 473
- https://doi.org/10.3390/genes11050473
Abstract
Inherited retinal dystrophies are an assorted group of rare diseases that collectively account for the major cause of visual impairment of genetic origin worldwide. Besides clinically, these vision loss disorders present a high genetic and allelic heterogeneity. To date, over 250 genes have been associated to retinal dystrophies with reported causative variants of every nature (nonsense, missense, frameshift, splice-site, large rearrangements, and so forth). Except for a fistful of mutations, most of them are private and affect one or few families, making it a challenge to ratify the newly identified candidate genes or the pathogenicity of dubious variants in disease-associated loci. A recurrent option involves altering the gene in in vitro or in vivo systems to contrast the resulting phenotype and molecular imprint. To validate specific mutations, the process must rely on simulating the precise genetic change, which, until recently, proved to be a difficult endeavor. The rise of the CRISPR/Cas9 technology and its adaptation for genetic engineering now offers a resourceful suite of tools to alleviate the process of functional studies. Here we review the implementation of these RNA-programmable Cas9 nucleases in culture-based and animal models to elucidate the role of novel genes and variants in retinal dystrophies.Funding Information
- Instituto de Salud Carlos III (PI16/00539, PI19/00303, CM18/00199)
- Generalitat Valenciana (PROMETEO/2018/135, ACIF/2019/252)
This publication has 160 references indexed in Scilit:
- RNA-Guided Human Genome Engineering via Cas9Science, 2013
- Evidence for reciliation of RPE1 cells in late G1 phase, and ciliary localisation of cyclin B1FEBS Open Bio, 2013
- A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial ImmunityScience, 2012
- Usher syndrome type 2 caused by activation of an USH2A pseudoexon: Implications for diagnosis and therapyHuman Mutation, 2011
- Retroviral-mediated Insertional Mutagenesis in ZebrafishMethods in Cell Biology, 2011
- A dominant mutation in RPE65 identified by whole-exome sequencing causes retinitis pigmentosa with choroidal involvementEuropean Journal of Human Genetics, 2011
- Self-organizing optic-cup morphogenesis in three-dimensional cultureNature, 2011
- A DNA Variant within the MYO7A Promoter Regulates YY1 Transcription Factor Binding and Gene Expression Serving as a Potential Dominant DFNA11 Auditory Genetic ModifierOnline Journal of Public Health Informatics, 2011
- A novel model of retinal ablation demonstrates that the extent of rod cell death regulates the origin of the regenerated zebrafish rod photoreceptorsJournal of Comparative Neurology, 2009
- Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsCell, 2006