Copy Number Variation, Epigenetics. Bio 400? No, NatGeo!

I was watching National Geograpghic HD last night. Yes, I do have a few minutes to watch TV. I always love to watch their in the womb specials. This time it was Twins.

What I love is the way they tell the story and teach the science (very lightly). I have to say, I have tried to teach doctors these subjects for a while now and most of what I get are these blank stares.

NatGeo has these wonderful graphic animations and weave a story around the animations with real clinical examples that bring the science to life.

Maybe we need to start having physicians watch NatGeo. We could scrub NCHPEG and anything EMedicine or UpToDate has to offer (which are average tools and topics).

Why? In one brief 60 minutes episode of NatGeo, they covered

1. Twins have epigenetic differences, explained epigenetics including methylation and presented Russell Silver syndrome in an Identical Twin

2. Identical Twins have different Copy Number Variation, yes they even explain what CNV is! BTW I mentioned this in the Autism studies being done up at Yale

3. They presented a MZ twin set where one boy was gay the other straight, v. interesting stuff on testosterone sensitivity.

They then took the fact that these people were identical and showed how based on these other subtle genetic differences they were at different risks for diseases.

This is probably one of the best ways to teach physicians, via case based learning and science. The big problem? Those episodes cost perhaps a million dollars to make. I don't see anyone handing over that kind of money in this economic environment. But what if they did? What if there was a channel just for physician education that produced such films? Sure the public could subscribe too.....what a great freakin' channel!

Yes, if we could have TV teach the physician we may be better off. Just an hour a night. 3 nights a week. Imagine how quick we could jumpstart the Personalized Medicine revolution. Turn off Grays Anatomy and tune into something worthwhile. But alas, most doctors are looking to escape medicine when they turn on the TV, not learn. But if you offered CMEs???? Might be something there....

The Sherpa Says: Why does it take a million dollar budget and a set of production professionals to create a palatable lecture on epigenetics? Alas, because the scientists and physicians have the Curse of Knowledge.

Ouch!! CNV with lackluster results....

All it takes is 2 seconds to step on some of my readership's toes and I feel it. Yesterday I posted on a 5% error rate for Whole Genome sequencing, I argued that even at 30x coverage it would not be ready for clinical diagnosis. I had CEOs of sequencing companies emailing me and VPs calling me. I even had pound for pound one of the best bloggers in the space say he was embarrassed for me.....Ouch!

Why do I get pushback from people, when all I am doing is throwing some cold water on the party???

Get ready, because I am about to throw some more.....Remember yesterday when I said SNPs were one of 7 or 8 factors that will differentiate each of us??? Well, CNVs are another of those 7 or 8, 2 more include histone modification and methylation, telomerase activity and size would be another factor, the rest I am saving for my own....for now. I first heard about CNV is 2006 when Mike Murray at Harvard keyed me into these guys, since then I have been following the literature and hoping we could get some results....well, we have but......

Here's the cold water, CNVs are not everything either, despite what some very learned people say.....just like genetic and genomic testing is only PART of the armamentarium for a personalized medicine specialist, CNVs are only part of the story.

True, we may find some very high Odds Ratios and some very specific diagnostics in the CNV space.....unfortunately, the American Journal of Human Genetics lays an egg with a chinese study of osteoporosis CNVs that lead to an Odds Ratio of 1.7 for osteoporotic hip fracture. I was hoping some of these CNV stories would be much more exciting than SNPs....My guess is that alot of the SNPs that we found previously with GWAS may actually just be markers for CNVs....and if that is the case, can we expect that much more from CNV than SNP?

I know some who would say yes, and I look forward to their comments. I think we may see this as the key in some areas, where amount of transcript plays a huge role, like metabolism of compounds or perhaps in cell signalling and migration events, but what about diseases that don't need that so much, structural protein diseases, ciliopathies, etc......

Most importantly, what about the diseases that sneak up on us over time like diabetes or atherosclerosis? I don't think that these will be the answer here. I have a very strong feeling that my equation Genome + Environment = Phenome + Metabolome will still hold true....

The one thing I am certain of is how to make things clinically applicable and right now, CNVs, SNPs, or Whole Genome Scans....there are only a very few limited cases where we can use this stuff......Until the sequencing companies are willing to take the liability for how their product are used, there are going to be problems trying to sell it as medicine without medical professionals......

So sorry to GC, PM, CV, JR, DM and who ever else decided to email me or call me expressing their problems with my cold shower: shake it off, look for solutions and get back to climbing the mountain.

The Sherpa Says: I just want to keep the marketers from overhyping.....Because if we don't, they will "create" our science.....Through slick words and number play published in the New York Times or Wall Street Journal.