International MPN News, Science & Opinion

Bare, Nake DNA

My 23andMe DNA Report

Last night, late, my Gmail inbox flashed the news: “Your 23andMe Results are Ready!”

Finally, I could see what all the fuss is about. And share it right here in the privacy of our MPNforum’s tabloid pages..

After making sure the curtains were drawn, I shooed the cat out of the room, checked the closets, looked under the desk and then closed the door securely. This may be all about MPN research, but that’s down the road a bit. What has been delivered to me for immediate attention is a thick stack of searchable data about that most intriguing of all subjects: Me. -­

My DNA has been unraveled enough to tell the story of my history, some of my traits, and my risk of acquiring one or more diseases. Could there be a more absorbing way to spend an evening or two?

Admittedly this may be less interesting to you but, if you intend to go down this path you can at least get a glimpse of what’s in store when 23andMe rings your bell and uncovers your own deep past and lifts the curtain to your possible future.

I opened the computer file and scrolled down first to check out my ancestors. Just out of respect, you know. There they were, scowling and winking back at me:

Dad: J2a1b1

Mom N1b2

Choked me right up. My haplogroup. Tomorrow, I might have a gold medallion stamped with those magical characters. And hang it on a gold chain around my neck,. Think of it. J2a1b1 and N1b2 stitched on a sampler, framed, placed in a niche with candles and incense burning before it.

Naturally I was taken a bit aback when I realized I was the product of a mixed marriage. Worse, there is an off chance that a future stormtrooper will force me to wear those symbols stitched to a piece of yellow cloth Because, for all the differences in my maternal and paternal lines, their long common history is plainly written in my genes. Officially, I am a total Jew. It says so in black and white. A Sephardic and Ashkenazi Jew mixed in one package.

That wasn’t the surprising part as my mohel let me know that right from the painful beginning. My father was born in Russia, my mother in New York but for four centuries before that both families lived within 50 versts of each other in a much contested bloody strip of land on the shifting Northwestern borders of Russia. The surprising part was my chromosome ancestry record on both sides is 99% identical. (You can CLICK to enlarge those exhibits.)

The usual assumption among many Jews is we lived happily in the Holy Land, some making sacrifices, some changing money in the Temple, until booted out in the bloody Roman wars just after the time of Jesus. How we went from the desert to the freezing forests of Poland is the source of countless fairy tales and at least one good Broadway musical.

The stark haiku of my 23andMe haplogroup report, however, fleshes out a different story, a story of two migrations. The first took Dad J3a2b2 and the northern tribes of Samaria to Nineveh after a massive defeat to Sennacherib and the Assyrians. Shortly afterward these nomadic tribes emerged as the Jewish Khazars in the Caucasus. Their comings and goings alongside the Huns camped between the Caspian and Black seas, show up in my 23andMe ancestry map..

Several centuries later, the Judean migrations, ethnic cleansing encouraged by Titus and his Roman legions, drove Mom N1b2 to New York City and Tel Aviv via North Africa and Europe. All this is written in the Book of DNA, translated by 23andMe. Having spent years in the Moffitt Library and the Russian steppes tracking this history down, I can only marvel at the record revealed so easily. All that sweat, vodka and troika miles when the whole story can now be read in a drop of spit.

Predisposition to disease

I pulled myself out of the history book of my genome and turned to read some possible future scenarios. This is the much discussed “dangerous” part of the 23andMe Report….our predispositions, risk factors for disease, based on association of certain disease states with specific genetic markers uncovered in controlled studies. This is the stuff we’re supposed to keep out of the hands of insurance agents, employers, and prospective dates for an evening of light entertainment.

Good start: High probability, no disease

To start with, I had a good feeling for the reliability of this section since the top two conditions for which I am at high risk – psoriasis and rheumatoid arthritis, neither of which I do have – share a JAK-STAT pathway with myelofibrosis, which I do have. (There’s a bit about that in the Ruxolitinib report.)

I’ll spare you the walk down the whole menu of diseases – but do e-mail me if you’re interested in anything specific, I’d be happy to reveal all. I do want to focus in on just one that interested me: Thyroid cancer.

Thyroid cancer

I have Grave’s Disease, a nasty condition that sends the thyroid into overdrive along with the circulatory system, knocks out the body’s thermostat and pops out eyes among other exciting visual effects. It was brought under control when my thyroid was iodine irradiated which I’m reasonably sure sent me down this MPN path some 22 years ago. But 23andMe knows nothing of that. I have not yet filled out a survey. They have my name, date of birth and e-mail address.

The Thyroid Cancer page in the Disease Risk section is more like a chapter than a page. You open up to a short discussion of the thyroid, complete with function, incidence of thyroid cancer cases each year in the United Sates, followed by a “Preliminary Research report on 3 markers.”

These markers are short areas of DNA, SNPS that have been found to be associated with a predisposition for thyroid cancer. Just for a refresher, SNPs (pronounced SNIPS) are single nucleotide polymorphisms. Nucleotides are one of those letters that make up DNA. (OK, they’re not letters in real life but complex molecules denoted by single letters) . Each letter represents a molecule making up one half of a base pair that encodes our genome in that famous double helix chain of Watson and Crick. A, adenine, forms a base pair with T, thymine and G, guanine forms a base pair with C, cytosine. Those four letters – plus U, Uracil in RNA – is all of it, all our traits, all the code that goes into manufacturing each of us. And why two letters? Separate contributions from Mom and Dad.

Behind three doors

The report on thyroid cancer looks at three SNPs. In each case you get your ranking – high, average, low – and the impact of the anomaly,

Thyroid Report -- CLICK to enlarge

for example a T in the wrong place. You also get a reference to the source document that uncovered the association between the SNP and disease, and the odds of developing the disease based on the variation.

Behind the first door

SNP 1: Marker rs944289. The wild card here is the T. Each T increases the odds of thyroid cancer by about 1.4 times. Here, I hit the jackpot. Two T’s, nearly three times the average risk. The source study, published in Nature Genetics involved 1006 patients or European ancestry and 38,346 healthy controls. Julius Gudmundsson, et al., published in 2009

SNP 2: Marker rs965513 Here the Black Queen is the A. Each A increases the odds of thyroid cancer by 1.8 times. I slip into average risk with an AG, but still that A gives me nearly double the risk. Julius Gudmundsson did this research as well, same publication, different patient group, 962 Europeans, same controls. .

SNP 3: Marker rs2961920 Now we’re looking at papillary thyroid cancer, 608 patients and 901 healthy controls. The poison pill in this SNP is the combined AC genotype. Carry that SNP and you have three times the odds of thyroid cancer as the lowest ranking CC and 1.5 times that of mid ranking AA. This is a new investigator, Jazdzewski K et al. (2008) publishing in the Proceedings of the Natl Acad Sci. USA . I place right in the middle, double the risk of CC and half the risk of AC.

That’s it? This is the news we’ve been fighting over?

What have I learned? I think the report shows an elevated risk for thyroid cancer. Thyroid cancer isn’t that common — about 3% of all cancers — and there’s a high survival rate for most common thyroid cancers.

I check my reactions.

Strongest reaction Rushing down to the ER, report in hand.

Medium reaction Something to be aware of but no actio.n required

Minimal reaction Whatever. Toss it.

My strongest reaction is none of the above. At best I’m mildly interested. But how is it possible not to be impressed with the quality and depth of 23andMe’s work. After reading about the dangers of providing DNA results directly to consumers and the importance of having a mediating physician to interpret results, I wonder what alternative universe other people live in.

My own physicians rarely ask me to remove my shirt. I can’t remember the last time I sat in a waiting room with one of those open paper robes on. Mostly it’s an interview and a lot of computer keyboarding after an assistant records my blood pressure temperature and weight . The 23andMe report goes beneath the skin, into the nucleus of the cell, counts the sequence of molecules in key SNPS, pulls out anomalies that indicate demonstrated or suspected health effects and presents findings in a careful, balanced, sane way. What’s there to argue about? Even N1b2 didn’t do that for me when I was kid.

Double checking

There is a chance, of course, they just make this stuff up. Slim, but considering the passionate stances taken by folks over the 23andMe MPN initiative why not put to bed any eventuality. Actually, anyone can easily do it. Just Google the SNP number.

To confirm the quality of 23andMe data, I went to sources quoted in the report and to independent large scale NIH databases, SNPedia, GenBank, then to the articles in Nature Genetics, the research studies prepared by Julius Gudmonsson and took an independent readings on thyroid cancer from the Cleveland Clinic. Try it yourself.

It all checks out.

About the only new information I got googling around was that SNP Rs2961920 is part of Gene MIR146A on Chromosome 5. Now I do feel better knowing my SNP has a permanent home address but that’s about it. I’m pretty sure 23andMe wasn’t withholding this information.

Traits

There are other aspects to the 23andMe report and service but one that most of us will turn to is an assessment of our traits based on our genes. I found this one slightly off in some cases but absolutely mind blowing in one instance.

Despite my famed much-discussed great wealth, I was concerned over a $91 water bill I received from the City…along with a reminder that “It is not necessary to flush for everything.” With that in mind, I can’t tell you how stunned I was when I turned to TRAITS and there, right up top, right hand column, it clearly said “DOESN”T FLUSH” How on earth could they know this?

Alcohol Flush Reaction Does Not Flush

Note: There is another way for you to get a realistic sense of what’s these reports actually contain so you can judge for yourself. Just go to www.23andme.com and type Demo in the search box.
Take me back.

© Zhenya Senyak and MPNforum.com, 2011. Unauthorized use and/or duplication of this material without express and written permission from this blog’s author and/or owner is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Zhenya Senyak and MPNforum.com with appropriate and specific direction to the original content.

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