Monday, December 30, 2013

Your brain has many genomes.

Life used to be simple. We had one set of genes, found in all cells of the body. Skin cells, liver cells, and brain cells were different only because different subsets of those genes were expressed appropriate to each organ. Now, it is turning out that one organ, like the heart, may be governed by one set of genes (genome) while the brain may be run by a mosaic of other genomes generated by somatic mutations, (as opposed to germline mutations that are inherited and found in every body cell.) Psychiatric genetic studies generally have assumed mutations in red blood cells would also appear in the brain, but mutations unique to brain genomes have now been found.

Thomas Insel, who is head of the National Institute of Mental Health, has written a paper on this situation titled “The dark matter of psychiatric genetics.” Here is his abstract:

Although inherited DNA sequences have a well-demonstrated role in psychiatric disease risk, for even the most heritable mental disorders, monozygotic twins are discordant at a significant rate. The genetic variation associated with mental disorders has heretofore been based on the search for rare or common variation in blood cells. This search is based on the premise that every somatic cell shares an identical DNA sequence, so that variation found in lymphocytes should reflect variation present in brain cells. Evidence from the study of cancer cells, stem cells and now neurons demonstrate that this premise is false. Somatic mutation is common in human cells and has been implicated in a range of diseases beyond cancer. The exuberant proliferation of cortical precursors during fetal development provides a likely environment for somatic mutation in neuronal and glial lineages. Studies of rare neurodevelopmental disorders, such as hemimegencephaly, demonstrate somatic mutations in affected cortical cells that cannot be detected in unaffected parts of the brain or in peripheral cells. This perspective argues for the need to investigate somatic variation in the brain as an explanation of the discordance in monozygotic twins, a proximate cause of mental disorders in individuals with inherited risk, and a potential guide to novel treatment targets.

1 comment:

Deric Bownds said...

I want to pass on Jochen Fromm' comment made via Google+ :

Our brain is also based on the phenotypes of many "cultural" genomes. Our language, our culture, our religion, they all come along with rules, customs and norms that are stored in the neural connections of our brains. Cultural genes - some call them memes - are often expressed during rituals, meetings and classes. The main purpose of the periodic church services for example is to express cultural/religious genes, which happens during the sermon: the data encoded in the genes is read, translated and stored in cell body, i.e. the brains of the group members.

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