A Novel Chromosomal Translocation Identified due to Complex Genetic Instability in iPSC Generated for Choroideremia.
Cell Differentiation
/ genetics
Cells, Cultured
Cellular Reprogramming
/ genetics
Choroideremia
/ genetics
Chromosomes, Human, Pair 12
/ genetics
Chromosomes, Human, Pair 20
/ genetics
Chromosomes, Human, Pair 5
/ genetics
Humans
Induced Pluripotent Stem Cells
/ pathology
Karyotype
Retinal Dystrophies
/ genetics
Siblings
Translocation, Genetic
/ genetics
choroideremia
genetic instability
induced pluripotent stem cells
inherited retinal dystrophies
retinal differentiation
underprenylated cell phenotype
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
11 09 2019
11 09 2019
Historique:
received:
13
08
2019
revised:
28
08
2019
accepted:
07
09
2019
entrez:
14
9
2019
pubmed:
14
9
2019
medline:
12
5
2020
Statut:
epublish
Résumé
Induced pluripotent stem cells (iPSCs) have revolutionized the study of human diseases as they can renew indefinitely, undergo multi-lineage differentiation, and generate disease-specific models. However, the difficulty of working with iPSCs is that they are prone to genetic instability. Furthermore, genetically unstable iPSCs are often discarded, as they can have unforeseen consequences on pathophysiological or therapeutic read-outs. We generated iPSCs from two brothers of a previously unstudied family affected with the inherited retinal dystrophy choroideremia. We detected complex rearrangements involving chromosomes 12, 20 and/or 5 in the generated iPSCs. Suspecting an underlying chromosomal aberration, we performed karyotype analysis of the original fibroblasts, and of blood cells from additional family members. We identified a novel chromosomal translocation t(12;20)(q24.3;q11.2) segregating in this family. We determined that the translocation was balanced and did not impact subsequent retinal differentiation. We show for the first time that an undetected genetic instability in somatic cells can breed further instability upon reprogramming. Therefore, the detection of chromosomal aberrations in iPSCs should not be disregarded, as they may reveal rearrangements segregating in families. Furthermore, as such rearrangements are often associated with reproductive failure or birth defects, this in turn has important consequences for genetic counseling of family members.
Identifiants
pubmed: 31514470
pii: cells8091068
doi: 10.3390/cells8091068
pmc: PMC6770680
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors have no conflict of interest to declare.
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