title: A novel system for correcting large-scale chromosomal aberrations: ring chromosome correction via reprogramming into induced pluripotent stem cell (iPSC).
abstract: Approximately 1 in 500 newborns are born with chromosomal abnormalities that include trisomies, translocations, large deletions, and duplications. There is currently no therapeutic approach for correcting such chromosomal aberrations in vivo or in vitro. When we attempted to produce induced pluripotent stem cell (iPSC) models from patient-derived fibroblasts that contained ring chromosomes, we found that the ring chromosomes were eliminated and replaced by duplicated normal copies of chromosomes through a mechanism of uniparental isodisomy (Bershteyn et al. 2014, Nature 507:99). The discovery of this previously unforeseen system for aberrant chromosome correction during reprogramming enables us for the first time to model and understand this process of cell-autonomous correction of ring chromosomes during human patient somatic cell reprograming to iPSCs. This knowledge could lead to a potential therapeutic strategy to correct common large-scale chromosomal aberrations, termed "chromosome therapy".
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
authors.forename: Taehyun
authors.initials: T
authors.lastname: Kim
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Plona
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA. ajw168@case.edu.
authors.forename: Anthony
authors.identifier: 0000-0002-2780-1540
authors.initials: A
authors.lastname: Wynshaw-Boris
mesh_terms: D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology; D012303:Ring Chromosomes; D024182:Uniparental Disomy / Q000235:genetics
keywords: Chromosome therapy; Compensatory uniparental disomy (UPD); Genome editing; Induced pluripotent stem cells (iPSCs); Large-scale aberration; Ring chromosomes