Transcriptomics of the fetal human brain

A cutting-edge application of the Affy total human exome GeneChip (4X coverage per exon, 40X coverage per gene): Functional and Evolutionary Insights into Human Brain Development through Global Transcriptome Analysis.

From the News and Views, I was intrigued to learn that previous transcriptome analyses of adult human brains found very little difference in gene expression between brain areas:

[…] this suggests that it is the gene expression during development that largely determines higher brain functions by specifying the complexity of neural connections. Numerically, the most important genes relating to cognitive differences between species may be genes that specify how the machinery is put together. In support of this hypothesis, many of the identified differentially expressed genes in this study are related to processes involved in connection formation, such as axonal guidance and cell adhesion.

An impressive 76% of all human genes are expressed in the developing fetal brain. Of those, 33% are differentially expressed over brain regions (13 regions were examined) and 28% are alternatively spliced. The differentially expressed genes are also ones that seem to have evolved the most recently. Even in these early (midgestation) stages, left-right asymmetry was seen, such as the localization of the language-associated FOXP2 genes to Broca’s area.

Of interest to computational folks, they find that gene expression follows power-law scaling (as many other naturally occurring “small-worlds” networks do) with certain hub genes connected to many others and certain spoke genes with relatively few connections. Unsupervised hierarchical clustering is used in this analysis.

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