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Proc Natl Acad Sci U S A. 2004 Oct 12;101(41):14972-7. Epub 2004 Oct 4.

A comparative analysis of transcribed genes in the mouse hypothalamus and neocortex reveals chromosomal clustering.

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  • 1Howard Florey Institute, University of Melbourne, Parkville 3052, Australia.


The hypothalamus and neocortex are subdivisions of the mammalian forebrain, and yet, they have vastly different evolutionary histories, cytoarchitecture, and biological functions. In an attempt to define these attributes in terms of their genetic activity, we have compared their genetic repertoires by using the Serial Analysis of Gene Expression database. From a comparison of 78,784 hypothalamus tags with 125,296 neocortical tags, we demonstrate that each structure possesses a different transcriptional profile in terms of gene ontological characteristics and expression levels. Despite its more recent evolutionary history, the neocortex has a more complex pattern of gene activity. Gene identities and levels of gene expression were mapped to their chromosomal positions by using in silico definition of GC-rich and GC-poor genome bands. This analysis shows contrasting views of gene activity on a genome scale that is unique to each brain substructure. We show that genes that are more highly expressed in one tissue tend to be clustered together on a chromosomal scale, further defining the genetic identity of either the hypothalamus or neocortex. We propose that physical proximity of coregulated genes may facilitate transcriptional access to the genetic substrates of evolutionary selection that ultimately shape the functional subdivisions of the mammalian brain.

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