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Cerebral Cortex 2006 16(Supplement 1):i18-i25; doi:10.1093/cercor/bhk026
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Genomic and Evolutionary Analyses of Asymmetrically Expressed Genes in Human Fetal Left and Right Cerebral Cortex

Tao Sun1,4, Randall V. Collura2, Maryellen Ruvolo2,3 and Christopher A. Walsh1

1 Department of Neurology, Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA, 2 Department of Biological Anthropology, Laboratory of Molecular Evolution and 3 Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA, 4 Current address: Department of Cell and Developmental Biology, Cornell University Weill Medical College, 1300 York Avenue, New York, NY 10021, USA

Address correspondence to email: cwalsh{at}bidmc.harvard.edu.

In the human brain, the left and right hemispheres are anatomically asymmetric and have distinctive cognitive function, although the molecular basis for this asymmetry has not yet been characterized. We compared gene expression levels in the perisylvian regions of human left–right cortex at fetal weeks 12, 14, and 19 using serial analysis of gene expression (SAGE). We identified dozens of genes with evidence of differential expression by SAGE and confirmed these by quantitative reverse transcriptase–polymerase chain reaction. Most genes with differential levels of expression in the left and right hemispheres function in signal transduction and gene expression regulation during early cortical development. By comparing genes differentially expressed in left and right fetal brains with those previously reported to be differently expressed in human versus chimpanzee adult brains, we identified a subset of genes that shows evidence of asymmetric expression in humans and altered expression levels between chimps and humans. We also compared the coding sequences of genes differentially expressed between left and right hemispheres and found genes that show both asymmetric expression and evidence of positive evolutionary selection in the primate lineage leading to humans. Our results identify candidate genes involved in the evolution of human cerebral cortical asymmetry.

Key Words: brain asymmetry • evolution • human and chimpanzee • SAGE • differential gene expression • LMO4


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