passionless Droning about autism

Hello friends –

A while ago I saw a completely fascinating Nova  called Ghost In Your Genes concerning the nascent field of epigenetics, the study of the relative expression of genes, which is a bit different than the presence or absence of genetic differences.   I’d recommend this program to anyone interested in learning.

In a general sense, our genes are simply blueprints for the production of proteins; the traditional model of genetic research involves structural changes in the genetic blueprints, so that we might understand that a person with a particular mutation might produce more, or less, of a particular protein than someone without that mutation.  As protein gradients are altered, physiological effects accumulate, and we can begin to associate genetic differences with identifiable classifications.

But.  It turns out, structural differences in the DNA aren’t the only way to affect the production of genes.  Genes can also be regulated by a variety of factors, and these changes in regulation, in turn, are measured as expression of genes, essentially a measure of which genes are active, or inactive, and to what extent.

From Wikipedia:

In biology, epigenetics is the study of inherited changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence, hence the name epi- (Greek: επί– over, above) –genetics. These changes may remain through cell divisions for the remainder of the cell’s life and may also last for multiple generations. However, there is no change in the underlying DNA sequence of the organism;^[1] instead, non-genetic factors cause the organism’s genes to behave (or “express themselves”) differently.^[2]

For another interesting write up, see this one by PZ Meyers; it gets technical quickly, but is a nice read.  Specific mechanisms aside, it is sufficient for our purposes that epigenetics is the study of how a variety of non structural changes can affect how our genes operate.

An analogy might of a series of car engines, sitting at idle.   All of them power a car, but at a structural level there are differences, most models are roughly generating the same amount of force at idle, but, for example, the Prius engine is generating much lower force than Porsche engine.   At a very general level, we might consider physical mutations of our genome and protein generation capacities to be equivalent to the difference between the Porshce and the Prius at idle.  But there are other means to affect the energy being put out by the engine, the accelerator, tweaking the cylinders, or a variety of other means. This is a big shift and weights heavily on the ‘genetic and environment interaction’ theme that gets a lot play in the autism realm.  Despite a lot of studies, and spectrums of dollars there have been very few findings involving autism genes that do anything but confer a very limited risk of a diagnosis.  Furthermore, a lot of the studies are finding that seemingly very common mutations are implicated, but with very delicate effects.  An example of this might be the MET genes, that have several neat papers (here, here, here), but the specific MET-C allele associated with autism is still very common, found in nearly fifty percent of everyone.  None the less, it is just a little more prevalent in the autism cohort, but the impact is very subtle, and likely dependent on the presence of a variety of other genes (or expression patterns), or other factors.  Excepting known genetic  conditions that confer great risk, but can be responsible for only a fraction of our autism, mutations such as Fragile-X or Rhett Syndrome, the vast majority of genetic findings impart small increases in risk.

But once we start looking at the wide array of different genetic expression in autism, it becomes clear that which genes you use, and to what extent, might be as important as which genes you are born with.  By way of example, a very cool paper out recently, “Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA, whose protein product is reduced in autistic brain ” that is available in full online and I would recommend to anyone interested in how analyzing epigenetic changes and the accompanying differential gene expression can teach us more about autism.  A lot of the press around this study involves the hope that eventually this kind of finding might lead a treatment opportunities, something I personally consider to be a long term goal that still faces significant technical hurdles; but it does gives us insight into the nature of autism, and the usefulness of the half truth ‘differently wired’ argument concerning autism treatments.

– pD

Note: Updated link to PZ.