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Integration-free induced pluripotent stem cells derived from schizophrenia patients with a DISC1 mutation

Molecular Psychiatry volume 16, pages 358–360 (2011)Cite this article

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Schizophrenia, a severe brain disease with a prominent genetic basis, has been suggested to have a neurodevelopmental origin.1 Although many candidate susceptibility genes for schizophrenia have been identified,2 access to human neural progenitors and neurons to study the biology of disease genes is very limited. Induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells of healthy subjects and patients,3 offer an unprecedented opportunity to recapitulate both normal and pathologic human development, thereby enabling a new approach to understanding human disease mechanisms.

Rare, large pedigrees in which a single genetic locus is likely to confer disease susceptibility have proven to be invaluable for the study of complex disorders.4 Disrupted-in-Schizophrenia 1 (DISC1) was initially identified at the breakpoint of a balanced t(1;11)(q42;q14) chromosomal translocation that segregates with schizophrenia, bipolar disorder and recurrent major depression in a large Scottish family.5, 6 Linkage and association studies of additional populations have provided independent evidence to support the DISC1 locus as a risk factor for major mental disorders.2 How DISC1 contributes to a spectrum of mental disorders is unknown. Studies from rodents have implicated DISC1 in many neurodevelopmental processes.7 The splicing and expression of DISC1 in postmortem brains from individuals with schizophrenia is abnormal.8 Little is known about the function of human DISC1, which is significantly different from the rodent gene.8 We have previously identified an American family with schizophrenia and a 4 bp deletion in DISC1 that appears to result in diminished DISC1 expression.9 Here, we report the derivation of multiple iPSC lines from two affected siblings of this family with the DISC1 mutation, and from a healthy individual.

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Authors and Affiliations

  1. Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    C-H Chiang, Y Su, Z Wen, H Song & G-l Ming

  2. The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    C-H Chiang, C A Ross, H Song & G-l Ming

  3. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Y Su, Z Wen, C A Ross, R L Margolis, H Song & G-l Ming

  4. Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    N Yoritomo, C A Ross & R L Margolis

  5. Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    C A Ross, R L Margolis, H Song & G-l Ming

Authors
  1. C-H Chiang
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  2. Y Su
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Correspondence to R L Margolis, H Song or G-l Ming.

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Chiang, CH., Su, Y., Wen, Z. et al. Integration-free induced pluripotent stem cells derived from schizophrenia patients with a DISC1 mutation. Mol Psychiatry 16, 358–360 (2011). https://doi.org/10.1038/mp.2011.13

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