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Rare single-nucleotide DAB1 variants and their contribution to Schizophrenia and autism spectrum disorder susceptibility.
Nawa, Yoshihiro; Kimura, Hiroki; Mori, Daisuke; Kato, Hidekazu; Toyama, Miho; Furuta, Sho; Yu, Yanjie; Ishizuka, Kanako; Kushima, Itaru; Aleksic, Branko; Arioka, Yuko; Morikawa, Mako; Okada, Takashi; Inada, Toshiya; Kaibuchi, Kozo; Ikeda, Masashi; Iwata, Nakao; Suzuki, Michio; Okahisa, Yuko; Egawa, Jun; Someya, Toshiyuki; Nishimura, Fumichika; Sasaki, Tsukasa; Ozaki, Norio.
Afiliação
  • Nawa Y; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • Kimura H; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. kimura.hiroki@med.nagoya-u.ac.jp.
  • Mori D; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • Kato H; Brain and Mind Research Center, Nagoya University, Nagoya, Aichi, Japan.
  • Toyama M; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • Furuta S; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • Yu Y; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • Ishizuka K; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • Kushima I; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • Aleksic B; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • Arioka Y; Institute for Advanced Research, Nagoya University, Nagoya, Aichi, Japan.
  • Morikawa M; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • Okada T; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • Inada T; Institute for Advanced Research, Nagoya University, Nagoya, Aichi, Japan.
  • Kaibuchi K; Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Aichi, Japan.
  • Ikeda M; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • Iwata N; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • Suzuki M; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • Okahisa Y; Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
  • Egawa J; Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
  • Someya T; Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
  • Nishimura F; Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Toyama, Japan.
  • Sasaki T; Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
  • Ozaki N; Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Hum Genome Var ; 7(1): 37, 2020 Nov 10.
Article em En | MEDLINE | ID: mdl-33298905
ABSTRACT
Disabled 1 (DAB1) is an intracellular adaptor protein in the Reelin signaling pathway and plays an essential role in correct neuronal migration and layer formation in the developing brain. DAB1 has been repeatedly reported to be associated with neurodevelopmental disorders including schizophrenia (SCZ) and autism spectrum disorders (ASD) in genetic, animal, and postmortem studies. Recently, increasing attention has been given to rare single-nucleotide variants (SNVs) found by deep sequencing of candidate genes. In this study, we performed exon-targeted resequencing of DAB1 in 370 SCZ and 192 ASD patients using next-generation sequencing technology to identify rare SNVs with a minor allele frequency <1%. We detected two rare missense mutations (G382C, V129I) and then performed a genetic association study in a sample comprising 1763 SCZ, 380 ASD, and 2190 healthy control subjects. Although no statistically significant association with the detected mutations was observed for either SCZ or ASD, G382C was found only in the case group, and in silico analyses and in vitro functional assays suggested that G382C alters the function of the DAB1 protein. The rare variants of DAB1 found in the present study should be studied further to elucidate their potential functional relevance to the pathophysiology of SCZ and ASD.

Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: Hum Genome Var Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: Hum Genome Var Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Japão