Academic Journal
Optical genome mapping of structural variants in Parkinson’s disease-related induced pluripotent stem cells
| Title: | Optical genome mapping of structural variants in Parkinson’s disease-related induced pluripotent stem cells |
|---|---|
| Authors: | Joanne Trinh, Susen Schaake, Carolin Gabbert, Theresa Lüth, Sally A. Cowley, André Fienemann, Kristian K. Ullrich, Christine Klein, Philip Seibler |
| Source: | BMC Genomics, Vol 25, Iss 1, Pp 1-12 (2024) |
| Publisher Information: | BMC, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Biotechnology LCC:Genetics |
| Subject Terms: | Optical genome mapping, iPSCs, Parkinson’s disease, Structural variants, Biotechnology, TP248.13-248.65, Genetics, QH426-470 |
| More Details: | Abstract Background Certain structural variants (SVs) including large-scale genetic copy number variants, as well as copy number-neutral inversions and translocations may not all be resolved by chromosome karyotype studies. The identification of genetic risk factors for Parkinson’s disease (PD) has been primarily focused on the gene-disruptive single nucleotide variants. In contrast, larger SVs, which may significantly influence human phenotypes, have been largely underexplored. Optical genomic mapping (OGM) represents a novel approach that offers greater sensitivity and resolution for detecting SVs. In this study, we used induced pluripotent stem cell (iPSC) lines of patients with PD-linked SNCA and PRKN variants as a proof of concept to (i) show the detection of pathogenic SVs in PD with OGM and (ii) provide a comprehensive screening of genetic abnormalities in iPSCs. Results OGM detected SNCA gene triplication and duplication in patient-derived iPSC lines, which were not identified by long-read sequencing. Additionally, various exon deletions were confirmed by OGM in the PRKN gene of iPSCs, of which exon 3–5 and exon 2 deletions were unable to phase with conventional multiplex-ligation-dependent probe amplification. In terms of chromosomal abnormalities in iPSCs, no gene fusions, no aneuploidy but two balanced inter-chromosomal translocations were detected in one line that were absent in the parental fibroblasts and not identified by routine single nucleotide variant karyotyping. Conclusions In summary, OGM can detect pathogenic SVs in PD-linked genes as well as reveal genomic abnormalities for iPSCs that were not identified by other techniques, which is supportive for OGM’s future use in gene discovery and iPSC line screening. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 1471-2164 |
| Relation: | https://doaj.org/toc/1471-2164 |
| DOI: | 10.1186/s12864-024-10902-1 |
| Access URL: | https://doaj.org/article/cef0b56f4f56419a8a23798df35cef52 |
| Accession Number: | edsdoj.f0b56f4f56419a8a23798df35cef52 |
| Database: | Directory of Open Access Journals |
| Full text is not displayed to guests. | Login for full access. |
| ISSN: | 14712164 |
|---|---|
| DOI: | 10.1186/s12864-024-10902-1 |
| Published in: | BMC Genomics |
| Language: | English |