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Brain genes change over time

7 November 2011
Appeared in BioNews 632

The brain is a genetic mosaic of nerve cells that differ from each other slightly and change over time, according to a new study published in the journal Nature.

Dr Geoff Faulkner, lead author of the study from the Roslin Institute in Edinburgh, Scotland, said: 'This research completely overturns the belief that the genetic make-up of brain cells remains static throughout life and provides us with new information about how the brain works'.

'If we can understand better how these subtle genetic changes occur we could shed light on how brain cells regenerate, how processes like memory formation may have a genetic basis and possibly link the activity of these genes to brain diseases'.

The changes are brought about by retrotransposons - mobile gene elements that are able to shuttle in and out of genes, copying and pasting themselves into different parts of the genome over time. Retrotransposons are most commonly found in plants, but also make up more than 40 percent of the human genome according to the most recent estimates.

Researchers from the Roslin Institute collaborated with scientists from the Netherlands, Italy, Australia, Japan and the USA to identify the sites into which retrotransposons insert themselves in brain cells.

Taking samples from just two brain regions involved in learning and memory (the caudate nucleus and hippocampus), the findings revealed almost 25,000 insertion sites. Of these, 7,700 contained L1 retrotransposons, the best-known subtype. A more surprising finding was that nearly 14,000 insertion sites contained the Alu family of retrotransposon - previously unknown to be present in brain cells.

Further investigation of the insertion sites found that many lie within genes that have integral roles for healthy functioning of the brain, or indeed preventing disease. These include tumour-suppressor genes that are frequently found to be faulty in brain tumours.

'We want to see how much variability there is in this phenomenon in the healthy human population, to evaluate if there is a correlation between retrotransposition frequency and brain tumor formation', said Dr Faulkner, 'and to see whether it is increased or reduced in Alzheimer's disease'.

Other genes in which retrotransposons were found are involved in signalling between brain cells, which could affect memory. While the hippocampus - where new nerve cells are produced - is where short-term memories are believed to be consolidated into long-term memories, the effect of retrotransposons on these processes is currently unclear.

Dr Faulkner told Scientific American: 'It is tempting to speculate that genetic differences between individual neurons could impact memory, but we have no evidence yet that this is the case'.

Dr Virginia Warren, assistant medical director for Bupa, also stressed the importance of not jumping to conclusions at this early stage: 'This area of research is still in its infancy and we need to be careful not to make too many assumptions. These findings provide the building blocks for understanding some basic mechanisms in the brain. They don't provide all the answers, but it's a good place to start'.

DNA gene find 'transforms' theories on how brain works
BBC News |  30 October 2011
Genetic make-up of brain changes throughout life
Bupa - Health in the News |  31 October 2011
Somatic retrotransposition alters the genetic landscape of the human brain
Nature |  30 October 2011
The Ductile Helix: "Jumping Genes" May Influence Brain Activity
Scientific American |  30 October 2011
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