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Posts Tagged ‘Genome’

Hey Yin, we have a genome and a brain … what’s the relaionship?

I dunno Yang.  Lets focus on variation.  Genome sequence variation can vary with the brain  … and … gene expression can vary with the brain  … however … genome sequence variation can vary with gene expression … but … here’s a paper showing that gene expression is under the control of genome sequence variation. Purrrr.

Hey Yin, the correlation between genome sequence variation and gene expression confuses me.  I mean, gene expression can change if the environment changes right?  Doesn’t this confound research that uses genome sequence variation?

Meow.

thanks for the pic noyfb.

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1/365 [dazed & confused]
Image by PhotoJonny via Flickr

pointer to: Daniel MacArthur and Neil Walker’s (@ Genetic Future bog) in-depth coverage of various critiques on the recent back-to-back-to-back Nature magazine trifecta (covered here) on GWAS results for schizophrenia.  Rough going for the global corsortia and a major f**king bummer for folks like myself who have been hoping that these vast studies would provide a solid basis for genome-based cognitive intervention strategies in the future.  Some of the discussion in the comments section points to the weakness in the diagnostic criteria, which is a topic also covered here recently.

Perhaps there is hope in the brain systems / imaging-based approaches that are taking off as genome technology spreads into cognitive and imaging science. Tough to scan 10’s of thousands of people however. Double F**K!

I guess DSM-based psychiatric genetics is just about dead for the time being.  The announcement of the soon to shutter deCODE Genetics and its 5-year stock price captures the failure of this endeavor.

decode1

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Backyard trampoline
Image by Kevin Steele via Flickr

For more than a decade, we’ve known that at least 95% of the human genome is junk – or junque – if you’re offended by the thought that “you” emerged from a single cell whose genome is mostly a vast pile of crap – or crappe – if you insist.  Hmmm, what is this crap?  It turns out to be a lot of random repeating sequences and a massive collection of evolutionary artifacts left over from the evolution of earlier genomes – mainly bits of retroviruses who once inserted themselves irreversibly into our ancestors’ genomes.  One subset of this type of – can we upgrade it from crappe to “relic” now? – is something we’ve labelled “autonomously mobile DNA sequences” or more specifically, “long interspersed nuclear elements (LINEs or L1s)”.  This class of DNA relic comprises more than 15% of the human genome (that’s about 3-5x more than the relevant genomic sequence from which you emerge) and retains the ability to pick itself up out of the genome – via an RNA intermediate – and insert itself into new places in the genome.  This has been observed to happen in the germ line of humans and a few L1 insertions are even responsible for genetic forms of humn disease (for example in the factor VIII gene giving rise to haemophilia).  The mechanism of transposition – or “jumping” as these elements are sometimes called “jumping genes” – involves the assembly of a certain type of transcriptional, transport and reverse-transcription (RNA back to DNA) apparatus that is known to be available in stem cells, but hardly ever  in somatic cells.

Except, it would seem, for the brain – which as we’ve covered here before – keeps its precious neurons and glia functioning under separate rules.  Let’s face it, if a liver cell dies, you just replace it without notice, but if neurons die, so do your childhood memories.  So its not too surprising, perhaps, that brain cells have special ‘stem-cell-like’ rules for keeping themselves youthful.  This seems to be borne out again in a paper entitled, “L1 retrotransposition in human neural progenitor cells” by Coufal et al., [doi:10.1038/nature08248].  Here the team shows that L1 elements are able to transpose themselves in neural stem cells and that there are more L1 elements (about 80 copies more per cell) in the hippocampus than in liver or heart cells.  So apparently, the hippocampus, which does seem to contain a niche of stem cells, permits the transposition or “jumping” of L1 elements in a way that the liver and heart do not.  Sounds like a fun place to be a gene!

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