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Transcriptome analysis of male–female differences in prefrontal cortical development

Molecular Psychiatry volume 14, pages 558–561 (2009)Cite this article

Human neuropsychiatric disorders that involve the prefrontal cortex show gender differences in age of onset, prevalence and symptomatology. Gender dimorphisms in human-brain development may include differential cortical expression of genes on both the sex chromosomes1, 2 and on the autosomes. Here we identify gender differences in gene expression during human cortical development that may illuminate the molecular basis of gender biases in vulnerability to brain disorders.

Using an unbiased discovery driven microarray approach and targeted quantitative PCR (qPCR; Supplementary Methods) we identified and verified gender differences after surveying the expression of 55 000 transcripts in the prefrontal cortex of humans ranging in age from 1 month to 50 years (Supplementary Table S1). We found 8061 transcripts changed in expression level during development of the frontal cortex (P<0.001; Supplementary Table S2). Developmental changes involved genes in numerous functional groups including metabolic, synaptic and intracellular signaling. Principle component analysis revealed that age accounted for ∼30% of the variance (Supplementary Figure S1), whereas gender accounted for ∼8%, RIN RNA integrity number ∼3%, and race, pH and Postmortem interval PMI <2%. Regression analysis (age and gene expression) captured most of the differences with >10 000 transcripts changing significantly with age (P<0.05). This extends previous findings from a study with older individuals that identified 540 age-regulated genes.3

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Authors and Affiliations

  1. MiNDS Unit, CBDB, NIMH, IRP, Bethesda, MD, USA

    C S Weickert & A B Richards

  2. Schizophrenia Research Institute (SRI), University of New South Wales, Prince of Wales Medical Research Institute, Sydney, Australia

    C S Weickert & D Sinclair

  3. Cardiodx, Palo Alto, CA, USA

    M Elashoff

  4. Institute of Biotechnology, University of Cambridge, Cambridge, UK

    S Bahn

  5. Department of Evolutionary Genetics, Max Plank Institute for Evolutionary Anthropology, Leipzig, Germany

    S Paabo & P Khaitovich

  6. Institute for Computational Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    P Khaitovich

  7. Stanley Medical Research Institute, 9800 Medical Center Drive, Rockville, MD, USA

    M J Webster

Authors
  1. C S Weickert
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  2. M Elashoff
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  3. A B Richards
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  4. D Sinclair
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  5. S Bahn
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  6. S Paabo
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  7. P Khaitovich
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  8. M J Webster
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Corresponding author

Correspondence to M J Webster.

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

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Weickert, C., Elashoff, M., Richards, A. et al. Transcriptome analysis of male–female differences in prefrontal cortical development. Mol Psychiatry 14, 558–561 (2009). https://doi.org/10.1038/mp.2009.5

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