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| Status |
Public on Sep 03, 2014 |
| Title |
Genome sequencing coupled with iPSC technology identifies GTDC1 as a novel candidate gene involved in Neurodevelopmental Disorders |
| Organism |
Homo sapiens |
| Experiment type |
Genome variation profiling by high throughput sequencing
|
| Summary |
We identified genomic structural alterations of six patients with signs of neurodevelopmental disorder (NDDs) that harbour chromosomal rearrangements using large-insert paired-end tag sequencing (DNA-PET). This technique allowed the refinement of chromosomal breakpoints and lead to the identification of seven disrupted genes (GNAQ, RBFOX3, UNC5D, TMEM47, NCAPG2, GTDC1 and XIAP). For one patient we filtered the entire panel of structural variations (SVs) with his parents and identified a unique SV that disrupted a single gene: GTDC1. We then validated the functional consequences of the chromosomal breakpoint disruption of GTDC1 by using patient-derived iPSCs. By differentiating these cells into neural progenitor cells (NPCs) and neurons, we interrogated the disease process at the cellular level and observed defects in the proliferation and glycosylation status of NPCs and also defects in neuronal maturation and function. We compared these results with GTDC1-deficient wild-type human NPCs and neurons, and observed similar phenotypic features as in the patient-derived cells which confirm that GTDC1 is involved in the patient’s phenotype. We show here that the combination of genomic screening with iPSCs technology provides a mechanistic insight into possible contributory effects of candidate genes implicated in NDDs and for personalized medicine.
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| Overall design |
Structural variations were identified by long insert DNA paired-end tag (DNA-PET) sequencing, a mate-pair sequencing approach.
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| Contributor(s) |
Hillmer AM, Cacheux V |
| Citation(s) |
24603971 |
| Submission date |
Oct 18, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Axel HILLMER |
| E-mail(s) |
ahillmer@uni-koeln.de
|
| Organization name |
University of Cologne
|
| Department |
Institute of Pathology
|
| Street address |
Kerpener Str. 62
|
| City |
Cologne |
| ZIP/Postal code |
50937 |
| Country |
Germany |
| |
|
| Platforms (2) |
| GPL9442 |
AB SOLiD System 3.0 (Homo sapiens) |
| GPL13393 |
AB SOLiD 4 System (Homo sapiens) |
|
| Samples (8)
|
| GSM1245589 |
Genomic DNA of neurodevelopmental disorder patient CD8 |
| GSM1245590 |
Genomic DNA of neurodevelopmental disorder patient CD14 |
| GSM1245591 |
Genomic DNA of neurodevelopmental disorder patient CD9 |
| GSM1245592 |
Genomic DNA of neurodevelopmental disorder patient CD5 |
| GSM1245593 |
Genomic DNA of neurodevelopmental disorder patient CD10 |
| GSM1245594 |
Genomic DNA of neurodevelopmental disorder patient CD6 |
| GSM1245595 |
Genomic DNA of neurodevelopmental disorder patient CD15 |
| GSM1245596 |
Genomic DNA of neurodevelopmental disorder patient CD16 |
|
| Relations |
| BioProject |
PRJNA223164 |
| SRA |
SRP031505 |
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