Inuk and me

In The Spittoon, 23andme’s blog, we are given the opportunity to compare some of our SNPs with those of Inuk, the man from 4000 years ago in Greenland who today officially became the first ancient human to have his genome almost completely sequenced (you can read here the article I published today in my newspaper, PÚBLICO - and if you don't read Portuguese you can read the Spittoon's post). I went and compared. Cool!

Image: Inuk by Nuka Godfredsen/Nature

Cancer risks revisited

The Spitton, 23andme’s blog, mentions a paper in Nature Genetics by Gloria Petersen from Mayo Clinic and colleagues which pinpoints several locations in the genome which may me associated with higher risks of developing pancreatic cancer – maybe the most lethal of all cancers.

Randy Pausch (photo), the computer scientist at Carnegie-Mellon U., died of it a year and a half ago. (Remember his famous and moving “Last Lecture”?)

I went and tried to evaluate my own risk by following the instructions in that post, which consist in looking at my raw genetic data from 23andme at the following SNPs (or point mutations): rs9543325 (on chromosome 13), rs3790844 (on chromosome 1) and rs401681 (on chromosome 5).

The results are not clear-cut.

At rs9543325, my genetic make-up (CT) corresponds, according to the study in Nature Genetics, to 1.23 times higher odds to get one day this type of cancer than if it were the most common one (TT).

At rs3790844, I’m AG e that lower my odss (it multiplies the typical odds by 0.75);

And at rs401681, I’m CC, which means typical odds – lower in particular, than those of ao people who are CT ou TT at this location, and who might also have higher odds, according to previous studies, of contracting melanoma and colorectal cancer.

But even this last SNP, in spite of my genetic configuration apparently being the best possible one, is a two-sided coin, since having one or two C’s in this position has been associated, also in previous studies, to higher odds of getting other types of cancer: basal cell carcinoma (a type of "benign" skin cancer, I had one removed last year, thank you very much), as well as lung, bladder, prostate (which doesn’t concern me), cervical and endometrial (lining of the uterus) cancer.

Enough!

(Image: all rights reserved)

Genealogical stalker

Genealogical stalkers are people who find our name in the publicly available records accessed by the search engine of an online genealogical database, become convinced that they are distantly or closely related to us and absolutely want to know who we are and to get to know us better.

One of the participants in a mailing list I subscribe to has actually experienced the phenomenon personally. The other day, she wrote to the list that a genealogical stalker had found her name on a well-known genealogy website and had then gone to the extent of phoning her mother (looking for her phone number, I suppose). The mother's number, by the way, is unlisted, which only highlights the level of obsession involved in the stranger's act.

Creepy but predictable, don't you think?

Alzheimer’s false scare

Icelandic company deCODEme, currently in financial straits, decided to offer clients of rival American company 23andme a nice Christmas present, allowing them to upload their 23andme raw genetic data to their website, at deCODEme.com, in order to, a few hours later, and at no cost whatsoever, have them (re)analized through the deCODEme looking glass. What a fine idea, I thought – and took instantly advantage of their offer.

Two unpleasant things then happened. First, my mitochondrial haplogroup (maternal line) suddenly changed radically. According to 23andme, I’m H7, but at deCODEme.com I was now K. Second, I was suddenly afforded the opportunity of knowing (but only apparently, as I have since learned) my lifelong-risk of getting Alzheimer’s Disease.

Concerning the first remarkable consequence of the deCODEme invite, almost immediately I received an email informing me that there had been a mistake in the interpretation of the mitochondrial data and apologizing for the inconvenience. I should wait a few days and everything would return to normal. By the way, I looked it up again this morning, and currently my mitochondrial haplogroup is back to H (simply H, which means it’s less informative than 23andme’s H7).

Concerning the second instance, I put off looking at my Alzheimer risk for days; I confess that I was afraid to see the results (you have to opt-in to access them). But this morning I learned that my inaction had probably been the best option – and for unexpected reasons: it turns out that, based on the 23andme results, deCODEme is unable to calculate that risk.

Only that didn’t keep some of those who had the audacity to opt-in to get really scary – and false – results! (see here). In short, the estimation of the risk is based on the detection of certain alterations in a gene called APOE, but 23andme doesn’t read the whole set needed to calculate it, which in this case makes the data useless – and sometimes exaggerated.

Currently, the opt-in option for Alzheimer’s has disappeared from my list of opt-in health conditions at deCODEme.com. But up till now, the company hasn’t offered any explanation for this, nor has it apologized for possibly scaring some people to death. I find this completely irresponsible.

Concerning myself, I learned something, though: I feel truly relieved not to have these results at hand for the time being, and I think that when the hour of truth comes, I may not have the courage to know it (the truth) with respect to certain particularly devastating diseases. I recently read a novel, Still Alice, by American neuroscientist-turned-writer Lisa Genova, about a case of early-onset Alzheimer’s. I manage to endure reality up to that point (I think the book is great), but if I get closer to it, I fear I might burn my wings...

Image: Drawing of neurons by Santiago Ramón y Cajal, 1899

Worries

When new scientific research is released, 23andme updates our genetic info with so-called “clinical reports”. The latest one of these didn’t please me at all.

The reason is I was told that my genetic risk of having something called atrial fibrillation (AF) is higher than average (20.5 percent instead of 15.9 percent in the general population). The estimated hereditary component of AF is around 60 per cent, which means that genes weigh more than environmental factors.

AF in itself is no big deal, but being a type of cardiac arrhythmia – and especially when combined with certain other risk factors (like hypertension or diabetes) – it increases the risk of having a stroke. And that I certainly find worrisome.

AF symptoms: palpitations (racing heart, which I experience not unfrequently); lack of energy (who doesn’t?). All this to say that although it doesn’t mean I have AF, it makes me wonder.

One way to reduce the risk of stroke is treatment with drugs that dilute the blood, preventing potentially dangerous clotting when the arryhtmia hits. One of those drugs is warfarin – and the biggest problem with this drug is determining the right dosage for each person. Too much of it can lead to internal bleeding, to little won't serve its purpose.

Precisely where warfarin is concerned, 23andme also provided me, some time ago, a piece of relevant information about the most likely reaction I should have to it if I ever had to take it. Once again, my genes say that I am apparently more sensitive than average to this drug – which means that I might have to take smaller quantities of it to be on the safe side.

For the first time since I had my genes tested at 23andme, I feel the need to talk about this to my doctor when I next see him. Is this the empowerment they’re always "selling" us as being THE big promise of personal genomics? For the time being, I feel mostly a little unnerved.

Good news

I received the following message, posted on Family Tree DNA website, through one of the mailing lists I subscribed:

"An academic research team, including our chief mtDNA scientist Dr. Doron Behar, is collecting mtDNA haplogroup H full sequence results for a population study. The study will update the haplogroup H tree and provide information on the distribution of subclades. Every sample used will help the research team to develop and resolve the H haplogroup tree. Your mtDNA full sequence results qualify for possible inclusion in this study."

Which means that Israeli scientist Doron Behar and his team are going to start analysing the details of the mitochondrial haplogroup (matrilineal descent) that goes by the letter H, to which I belong (my sub-haplogroup, or subclade, is H7, as I have already mentioned here). Finally!

I heard about Behar’s work for the first time in 2006 (he was then at Rambam Medical Center in Haifa), when he and his colleagues published an amazing paper in the American Journal of Human Genetics. As I already wrote in a previous post, through the genetic study of mitochondrial DNA, they discovered that nearly half of Ashkenazi Jews (“German” Jews) in the world today are descended from just four “founding mothers”, most likely Hebrew women from the Middle-East, who lived in Northern Europe, in what is now Germany, one to two thousand years ago.

Apparently, Behar, who as the message says is chief mitochondrial DNA scientist at Family Tree DNA (www.familytreedna.com), has now decided he has enough data to go on, from clients there, to undertake the same kind of study on haplogroup H. And he is inviting participation.

I think this is a fantastic example of how scientists can put to good use individual genetic data (without disclosing anybody’s identity) to further our understanding of the migration routes of human populations through the ages.

The message, though, is only visible to those who have had their mitochondrial DNA fully sequenced at FTDNA - and who belong to mitochondrial haplogroup H.

Since I tested with 23andme (which does not offer full sequentiation of mitochondrial DNA), I won’t be able to participate personally. But I’m really curious about what the results will reveal about my own past.

Image: Mitochondrial haplogroup H tree - Fonte: familytreedna.com

Paternal Haplogroup: I

My brother ended up doing the Y-chromosome genetic test to determine our direct patrilinear descent (and I thank him dearly for that). The answer that came back a few days ago from GenoMed, the Lisbon-based company which carried out the test, was: haplogroup I (defined by a single mutation called M170).

The GenoMed site explains:

“The first populations belonging to group I originated in Southern Europe, immediately before the last Ice Age. Their ancestors arrived in Europe through a migration route starting in the Middle East and ending in the present-day region of the Balkans. (…) During the Ice Age (20 to 12 thousand years ago), these populations remained confined to climatic refuges predominantly situated on the shores of the Dead Sea and in the Balkans. Later, when climatic conditions improved, (…) they started reclaiming the land and spreading their offspring all over Europe.”

Then:

“Today, group I represents nearly one fifth of the European genetic pool. (…) Group I lineages predominate in Scandinavia and in the Balkans. The highest frequencies (nearly 40%) are detected in the populations of Herzegovina, Croatia, Bosnia, Sardinia and Scandinavia.”

And finally:

“The genetic group I is not usually associated to Jewish ancestrality.”

This last sentence reminded me of a memorable scene in the Woody Allen classic Annie Hall. In it, the main character, Alvy Singer, makes the following remark during a flashback to his childhood: “My grammy never gave gifts. She was too busy getting raped by Cossacks.”

I apologize to all those who might be shocked by the very bad taste of this joke, by its political incorrectness, etc., etc.. But the truth is that the idea Allen was playing with in that sentence undoubtedly corresponds to the tragic reality experienced by many Jewish families during the blood-shedding pogroms that took place in Ukraine and Poland during the nineteenth century and the beginning of the twentieth (and forced so many Jews to emigrate to the Americas).

As far as I know, luckily nothing of the sort happened to any of my grand-mothers, great-grandmothers and great-great-grandmothers – but before that, I can’t guarantee it didn’t.

My family’s genes might thus be telling a story of persecution and violence.

Image: DNA Root Tester