my impression is that much of the "penetrance" effect of many deleterious genotypes (that is, don't get sick sometimes, do other times) have to due with epigenetic probabilities. so, my ? is how much do we really know about epigenetics in humans? are there seminal review articles? i've seen stuff on a family with a particular disease and weird penetrance patterns and different patterns of methylation, but it seems all over the place.

Epigenetic differences arise during the lifetime of monozygotic twins.

http://www.pubmedcentral.gov/ art...bmedid=16009939

check it out if you haven't seen the full text

tx. that's what i was looking for!

some others:

http://hmg.oxfordjournals.org/ cg...ink_type=PUBMED
http://hmg.oxfordjournals.org/ cg...ink_type=PUBMED

So, for the layman - could this help explain (partially) those sometimes huge "this should be environmental influence, but we can't pinpoint what it is" factors from twin studies, etc?

Fanatastic!
really enjoyed this - and learnt something new
thanks

I'd be skeptical. Worms are much smaller than humans, and much more R in their selection strategy, suggesting that much more noise is likely. Organisms that follow a K selection strategy, and which have enough cells, even in a blastocyte, to statistically reduce noise to managable levels, probably do so.
By removing noise from an organism's development, they would remove noise from its selective fitness, enabling more efficient natural selection, which could be faster, conveying a long-term selective advantage. Even if they don't do this, they probably want to minimize noise because in general random deviation from a template is harmful.

some things to note:

Worms are small - less than 1000 somatic cells; meaning the per-cell frequency of errors may be higher while the total error load may not be

Their development is tightly regulated - their cell lineage is invariant between individuals; at the level of cell division and differentiation, they are physically identical

They are short lived - 2-3 weeks, depending on conditions; yet the variability in their lifespan is nearly as great as lifespan variation in humans in the US

What really sparks my curiosity is the idea that chance variation may be structured, so that seemingly disparate kinds of errors are correlated. With enough biomarkers, it may be possible to extract one or more statistical factors that predict variation in health, longevity, etc. This, I think, was completely unexpected. Instead we would have thought that variation was just the noise of mostly unrelated stochastic events. It's also interested that these variations exist despite the tight control over development. So, I think it's possible that these correlated variations are in some way regulated; or to put it in teleological terms: a design feature rather than a flaw.

Among humans, identical twins often develop different personalities precisely because they are in constant contact with each other -- e.g., one becomes the leader and the other the follower because it's easier to get things done that way, and it's not all that exploitative a relationship because the follower would probably make similar decisions if he was the leader. Heinlein's "Time for the Stars" has an insightful portrait of identical twins.

A confounding factor with MZ twins might be how the egg splits. Did the original egg divide evenly and were the same growth factors evenly distributed. Even the axis along which the egg divides could make a difference. Did one twin arise from a single cell after the egg had already divided several times? Some difference could be due to DNA methylation while others arise due to different concentrations of regulatory factors. (Or so it seems to me from my general reading.)

I think the interesting question is what proportion of twin differences are due to a few (relatively) random events that crystalize into large scale differences versus a constant stream of stochastic events nudging them apart.

If one twin received more organelles in the "split", or more blood supply from the placenta, and grew minutely larger, stronger, and smarter in the womb--almost all the post-natal differences would logically follow.

The stronger, smarter one would be the leader and dictate the terms of their co-evolutionary environment.

what proportion of twin differences are due to a few (relatively) random events that crystalize into large scale differences versus a constant stream of stochastic events nudging them apart.

yes, quantifying the dimensionality of the underlying stochastic process.

it will be good to take a second look at these reporters transplanted into hsp mutants -- the ones which have reduced buffering of developmental noise...