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Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer

Abstract

Defects in genetic and developmental processes are thought to contribute susceptibility to autism and schizophrenia. Presumably, owing to etiological complexity identifying susceptibility genes and abnormalities in the development has been difficult. However, the importance of genes within chromosomal 8p region for neuropsychiatric disorders and cancer is well established. There are 484 annotated genes located on 8p; many are most likely oncogenes and tumor-suppressor genes. Molecular genetics and developmental studies have identified 21 genes in this region (ADRA1A, ARHGEF10, CHRNA2, CHRNA6, CHRNB3, DKK4, DPYSL2, EGR3, FGF17, FGF20, FGFR1, FZD3, LDL, NAT2, NEF3, NRG1, PCM1, PLAT, PPP3CC, SFRP1 and VMAT1/SLC18A1) that are most likely to contribute to neuropsychiatric disorders (schizophrenia, autism, bipolar disorder and depression), neurodegenerative disorders (Parkinson's and Alzheimer's disease) and cancer. Furthermore, at least seven nonprotein-coding RNAs (microRNAs) are located at 8p. Structural variants on 8p, such as copy number variants, microdeletions or microduplications, might also contribute to autism, schizophrenia and other human diseases including cancer. In this review, we consider the current state of evidence from cytogenetic, linkage, association, gene expression and endophenotyping studies for the role of these 8p genes in neuropsychiatric disease. We also describe how a mutation in an 8p gene (Fgf17) results in a mouse with deficits in specific components of social behavior and a reduction in its dorsomedial prefrontal cortex. We finish by discussing the biological connections of 8p with respect to neuropsychiatric disorders and cancer, despite the shortcomings of this evidence.

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Acknowledgements

This study was supported by grants from the following: Spanish FIS-MSC Grant PI051293, the Spanish Ministry of Health, Instituto de Salud Carlos III, CIBERSAM and Fundación Alicia Koplowitz to RTS; and from Nina Ireland and NIMH R37MH49428-16 to JLRR. We thank Teresa Escámez, Juan Antonio Martínez-Giménez, Vicent Balanzá-Martínez, Salvador Martínez, Eduard Vieta and Manuel Gómez-Beneyto for their helpful advice on previous versions of the manuscript and for their excellent technical assistance.

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Correspondence to J L R Rubenstein.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Tabarés-Seisdedos, R., Rubenstein, J. Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer. Mol Psychiatry 14, 563–589 (2009). https://doi.org/10.1038/mp.2009.2

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  • DOI: https://doi.org/10.1038/mp.2009.2

Keywords

  • 8p
  • NRG1
  • FGF family
  • schizophrenia
  • autism
  • cancer

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