We have no clue what it really means....Merry Christmas

The scene, a roundtable of geneticists reviewing a case.

Geneticist 1: Well, some one (Non geneticist) astutely ordered genetic testing for condition X before we saw them. When we saw them we ordered a Chromosomal Micro Array (CMA) and a karyotype....

Geneticist 2: Well, did you ate least think of condition X?

Geneticist 1: Not really, it was pretty atypical for condition X so we thought we might find something with a CMA.

Geneticist 3: You'll certainly find things with a CMA. Now what the hell you will do with those rare deletions and duplication is another topic.

Geneticist 4 and Training Geneticist 5: "Chuckle, Chuckle"

Geneticist 1: Well, while we were waiting for the CMA, we were notified by the patient's family, they have condition X....

Geneticist 2: Wow, I would have thought it was Condition Y based on your presentation which would have been picked up on CMA.....

Geneticist 1: Well, we did pick up something on CMA...

Geneticist 5: Let me guess, a rare unknown duplication

Geneticist 1: Correct, how did you know???

Training Geneticist 5: 50-50 shot.

Geneticist 2: So now what will you do.

Geneticist 1: Same thing we always do. Test mother and father, if they're "normal" we will say it is a benign event......

Training Geneticist: Too bad we can't say "We have no clue what it really means....Merry Christmas"

Close scene....

Today this is happening at an alarming rate in clinical genetics services in academic centers everywhere.....

Here's the catch.....It will only get worse before it gets better, and it will take a very long time or 10 million people to make it better.

We really have no idea what is in store when we start looking at all these genomes....My guess is that even the smartest geneticist will be rendered a bumbling idiot at least 10 times in the next decade.....

The Sherpa Says: A smart entrepreneur finds solutions to this and many other problems that wil stem from this crazy genomic data......and when Francis becomes NIH director, the US will turn into DeCode/Iceland, it is the only way to figure this stuff out.....too bad the public isn't ready for it.....Franics is no Kari and the US is no Iceland....Merry Christmas!

Restless Legs and deCODE

In the New England Journal of Medicine next week there will be an article on yet another study done at deCODE. Their model may be that of the next wave of pharma companies. Personally, not a bad model, but imagine Pfizer sending press releases on all of their Phase one data. It would result in a lot of "white noise" that may or may not have some future health news. That seems to be what is going on in Reykjavik. At least they are getting their money's worth for the Icelandic genome.

In this study the research team conducted genome-wide scans of nearly 1,000 Icelanders and 188 Americans. A new chip technology was applied along with genome wide association methods. This approach allowed Drs. Rye and Stefansson to probe more than 300,000 small regions (single nucleotides) distributed across the entire genome for differences more common to RLS sufferers as compared to population-based controls.

The expedition was to find a gene linked to Restless Leg Syndrome. Sleep is often interrupted in these patients and can lead to a terrible lifestyle. There is a high prevalence of this disease in North America and Europe. Seemingly a Caucasian disease it was natural to look for this linkage in the Icelanders.

Here's what my Head Genomic Counselor had to say:
"They found an intronic SNP in the BTBD9 gene that has an OR of 1.7 for PLM (heterozygotes) and an OR of 2 – 4 for homozygotes for the A allele (vs. the wild type G allele).
The interesting thing is that it seems to be associated with PLM alone and RLS with PLM, rather than RLS without PLM.
They replicated the association in three independent patient groups – two in Iceland and one in the US. Seems like a good study from a design perspective."

What does that mean? Let me translate. The searched the genome of these Icelanders for genes linked with restless leg syndrome versus periodic leg movement disorder in sleep. RLS is a common neurologic disorder which involves both sensory and movement components. Identification of the genetic under pinnings in RLS has been difficult because of several confounding variables including other medical conditions. Periodic limb movements in sleep are a component of RLS. These movements can also be absent in the presentation of RLS.

The group found and replicated a non-coding change in a gene called BTBD9. This gene was also correlated with depleted iron stores. RLS has been long linked to iron deficiency and this makes this whole study "seem" to be correct.

The Sherpa Says: All this is fine and Dandy, but what clinical use will this finding hold. Personally, I feel that this is a confusing issue. The predisposition test would let us know something that we currently cannot prevent. Testing for this???? I wouldn't recommend it. But I am certain they will market this test just like the risk for atrial fibrillation. Not a bad model over there......too bad it could lead to misguided healthcare in the wrong hands. Why? Because who would tell you to take a blood thinner, just because you have a predisposition to atrial fibrillation? Only those doctors looking to get sued........