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Series GSE178646 Query DataSets for GSE178646
Status Public on Jun 23, 2021
Title CRISPR gene editing and inducible pluripotent stem cell neuronal disease modelling for rare disease diagnosis: EMHM1 genetic variant analysis in Kleefstra Syndrome
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Over 400 million people worldwide are living with a rare disease, with genetic variants determining 80% of cases. Next Generation Sequencing identifies potential disease causative genetic variants, however many of these are classified as variants of uncertain significance (VUS). Each VUS requires functional validation as pathogenic or benign in disease pathology in specialist laboratories creating major delays in patient diagnosis. In this study we test a rapid genetic variant assessment pipeline using an EHMT1 (Euchromatin histone methyltransferase 1; EHMT1 p.Gln1144Ter) genetic variant that is pathogenic for Kleefstra Syndrome. Precise CRISPR homology directed (HDR) gene editing introduced the single nucleotide genetic variant in iPS cells and EHMT1_SNV cell clones were rapidly identified with amplicon sequencing. Induction of neural differentiation and RNA sequencing determined differences in differentiation at the gene and transcription factor level. The applied CRISPR HDR methodology was rapid and reliable for the introduction of SNVs in iPSCs for subsequent neuronal cell differentiation. Key features of Kleefstra Syndrome were identified, with involvement of key transcription factors REST and SP1 in disease mechanisms. This study indicates that precise iPSC gene editing and changes in disease modelling pathways can contribute to disease diagnosis and understanding of mechanisms.
 
Overall design Comparison of CRISPR edited EHMT1_SNV and EHMT1_WT iPSCs via RNA sequending before and after induction of neural differentiation
 
Contributor(s) Fear VS
Citation(s) 35139903
Submission date Jun 22, 2021
Last update date Feb 18, 2022
Contact name Denise Anderson
E-mail(s) Denise.Anderson@telethonkids.org.au
Phone 0863191651
Organization name Telethon Kids Institute
Department Precision Health
Lab Computational Biology
Street address 15 Hospital Avenue
City Nedlands
State/province WA
ZIP/Postal code 6009
Country Australia
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (12)
GSM5395216 iPSC EHMT1_SNV CF1 cells
GSM5395217 iPSC EHMT1_SNV CF2 cells
GSM5395218 iPSC EHMT1_SNV CF3 cells
Relations
BioProject PRJNA739884
SRA SRP325023

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Supplementary file Size Download File type/resource
GSE178646_RAW.tar 71.8 Mb (http)(custom) TAR (of TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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