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

Should we fully share our genetic data?

I subscribed to a genetics mailing list and through it, I was asked on several occasions by other participants to send my raw genetic data for this or that chromosome (that is, the sequence of letters that resulted from my genetic testing).

A lot of people are interested in this kind of information, since certain comparisons between individuals can only be carried out using ad hoc software. There are many amateur geneticists out there – and some of them have developed little computer programs, more or less easy to use, to extract information from the raw DNA data – and which are of particular interest for the search of common ancestors when the people involved didn’t have their genes read by the same company.

I must confess that I have ignored these invitations/requests. I confess that the idea that my genome, even a mere part of it (or to be precise, of the 500 thousand letters of my DNA that were read by 23andme when I got tested) could be circulating in cyberspace, without my knowing exactly where, gives me the creeps.

A few days ago, however, I attached all of my raw data (to which I have access) to an email in order to participate in a scientific project that I find very interesting. But when, just for an moment, I thought I had sent it to the wrong email address (in fact, to the public mailing list I just mentioned), I became really nervous. Luckily, it was only a false alarm…

A few months ago, in an article in the New York Times, well-known scientist Steven Pinker asked himself what could be the consequences of publishing one’s genome (and in his case, his whole genome, since he is participating in a full-sequencing project).

His answer boiled down to this: if an insurance company ou any other entity wanted to to read secrets from our genes to infer our individual characteristics, the effort would be doomed from the start. Genes offer essentially statistical information, which apply to groups of people. And, apart from a few exceptions, their contribution to every disease and physical or psychological trait is almost inextricable.

“Many of the dystopian fears raised by personal genomics”, Pinker wrote, “are simply out of touch with the complex and probabilistic nature of genes. Forget about the hyperparents who want to implant math genes in their unborn children, the “Gattaca” corporations that scan people’s DNA to assign them to castes, the employers or suitors who hack into your genome to find out what kind of worker or spouse you’d make. Let them try; they’d be wasting their time.”

This is true in most cases. But what about those serious genetic diseases that depend on only one gene – and owing to which and insurance company, for example, could rapidly determine our individual propensity and deny us an insurance policy – or a potential employer refuse to give us a job? Even in that tiny bit of DNA contained in our mitochondria, which is used to determine our matrilineal ancestry, there are some disease genes – some of which haven’t yet been identified.

When I had my DNA tested and wrote about it, I knew I could be unveiling things that could one day “be used against me” in a worst-case scenario. After all, the exploitation of genetic data by third parties is virtually devoid of regulation. But I decided to take that risk because my curiosity was greater than my fear of the hypothetical risks involved – and because I thought it was important to write on the subject.

As to the scientific project I said I’m involved in – which is being done by scientists at Harvard I know that they will use it, together with that of many other people, to search for clues to the ancestrality of a community of people as a whole (I’ll say more about it one of these days). But they will not reveal any of my individual traits or results to anyone other than myself. To ensure this was clear on both sides, I had to sign several consent forms where they, on their side, specify extensively what they are and aren’t allowed to do with my genetic data.

But sending out my genetic “letter soup” in more informal terms is altogether a different matter: we know information can spread like a virus in the Internet and end up in the wrong hands. I’m utterly sure that the people who are asking me to send them parts of my raw data are well-intentioned – there’s absolutely no question in my mind about it. But I feel that accepting to do it means that I will cease to have control over that data. And for the time being, in spite of the remoteness of the risks this entails (in this I agree with Pinker), is a step I’m not ready for just yet.

Photo credit: Dollar Bin/Flickr

An interesting little sofware

EURO-DNA-CALC is a piece of software that allows anyone who’s been gene-tested by 23andme or its rival company, deCODEme in Iceland, to calculate the mix of Northwestern European, Southeastern European and Ashkenazi Jew any person of European descent carries in his or her genes.

I didn’t immediately understand how this worked. To download the program, you have to go to its inventor’s Dienekes Pontikos’ Anthropology Blog – more precisely here.

Calculations are based on data from a study by Alkes Price, of Harvard U. and colleages, published in 2008 in PLoS Genetics under the title: Discerning the ancestry of European Americans in genetic association studies.

In that study, the authors define Northwestern Europeans as people who originally came from Sweden, the UK or Poland, Southeastern Europeans as coming from Greece, Italy or (stretching the Compass Rose a bit) Spain, and Ashkenazi Jew as coming from the general region of modern-day Germany.

When you read the software’s README.txt file, you learn that you need to fetch another software, which is the one which will actually do the statistics and calculate the estimated contributions of each of those three ancestral populations to your genome. That’s the part that took me some time to figure out… But I eventually did; it’s all there, you just need to read it carefully.

Then you download your raw data file from one of the above mentioned company sites (both offer that functionality), and apply the software to the data exactly as specified in the instructions.

In my case, it came up with this pie chart:

And this caption:
> EuroDNACalc("23andme")
[1] "NORTHWEST EURO: Maximum Likelihood Estimate=17% Interval=[0, 34]"
[1] "SOUTHEAST EURO: Maximum Likelihood Estimate=0% Interval=[0, 36]"
[1] "ASHKENAZI JEWISH: Maximum Likelihood Estimate=83% Interval=[61, 100]"

I have no idea of the scientific validity of such a result – and I don’t even think it’s much use either, but there it is.

And the seven finalists are...

… seven other blogs.

I wasn’t selected for the final of the 3QD Science Prize 2009, despite my post being the second most voted by the public.

Many thanks to all those who voted for me!

Books from a lost world

A few days ago, I ordered two books which mention the town of Derazhnia, in Ukraine, where my paternal grand-mother, Mania Rosenblatt, was born in 1895.

The Nazis slaughtered the whole Jewish population in that town – around 4,000 people. Today, a few typical Jewish houses from that lost word are all that remains – together with a sort of stone pyramid that marks the site, in the nearby woods, of the massacre and of the mass grave where women, men and children were thrown, one on top of the other, after they were shot, some of them still breathing.

One of those books, The Road from Letichev - The history and culture of a forgotten Jewish community in Eastern Europe, by David A. Chapin and Ben Weinstock, is a detailed account, in two volumes, almost individual family by individual family, of the Jewish inhabitants of that area.

I also ordered a book of short stories by Yiddish author Sholem Aleichem (in English, Tevye's Daughters: Collected Stories of Sholom Aleichem) one of which, under the title “The German” that takes place in Derazhnia (which had a very important train station)

Last but not least, but on a different subject, Maurice Rosenblatt and the Fall of Joseph McCarthy, a book by journalist Shelby Scates from the Seattle Post Intelligencer. One of these day I will explain here what Maurice Rosenblatt – a famous lobbyist who was a central character in the fall of mccarthyism in America – and I have in common.

Photo credit: Alexandra Laignel-Lavastine

Journey to my Genes second most voted

Twenty science blog posts have been selected for the semi-finals of the 3QD 2009 Prize in Science.

As you can see here, My Genes and Me: Journey to My Genes, was the second blog post most voted by the public.

To all those who voted for it, my sincerest thanks.

On June 11, seven finalists will be announced – among which scientist Steven Pinker will then have to choose three winners by June 21.

Wish me luck!

Those never-ending lists

I’ve been trying for days (I should rather say nights) to find my father’s and his family’s names in the Hamburg ship lines passenger lists that sailed for Buenos Aires in the year 1925 (in this picture of the Nansen passport which allowed them to leave Poland, he’s the baby, on his mother’s lap, with his older brother on one side and an aunt on the other). The only clue I have for their emigration date is that my father was around six months old at the time – so they must have left at the end of that year.

The Ancestry.com website has all that stuff in a database – or rather, almost all of it, since for the period I’m looking at, they only have scanned images of the ledgers containing those records. They’ve been digitized with the best possible quality – which sometimes means no quality at all. Imagine thin, ancient pages, frequently glued together and full of ink blots. Some you can easily read, others are a mix of words written in both directions (the ink having passed through the paper or from one page to next), and they are basically unreadable. This last week-end, I browsed through a thousand or so pages, hand-written or typed, large, small, sometimes wrinkled (you can judge for yourself from the images below!). I haven’t found anything yet, but I’m planning to keep on reading. I’ve become somewhat knowledgeable at detecting potentially relevant data in this sea of paperwork.

Overturning the Mosaic Law through genetics

The rabbinical law of Israel, or Mosaic Law, considers as Jewish (even if he or she practices another religion, even if he or she doesn’t have a clue) anyone whose mother was Jewish, and who in turn had a Jewish mother, and so on and so forth, straight back to Adam and Eve (or rather, just Eve).

David Goldstein, from Duke University (whom I already mentioned), specializes in the analysis of mitochondrial DNA – that little bit of our genetic heritage that comes down to us exclusively from our mothers, and to them from their own mothers, etc. – that is, by direct matrilineal descent. And ironically, through genetic studies, Goldstein is questioning the traditional matrilineal view of Judaism.

Genetics revealed that there are currently a few scores of haplogroups (genetic lines) of mitochondrial DNA in the world, each one derived from a “founding mother” who lived thousands of years ago (and each one of these mothers being, in turn, a daughter of the “Mother of all Mothers”, the so-called mitochondrial Eve, who lived in Africa some 200 thousand years ago).

Through a genetic analysis of mitochondrial DNA, Goldstein discovered, in 2002, that the mitochondrial DNA of Jewish people appears to be derived from that of local populations living in Europe thousands of years ago – and not from any hypothetical Jewish “ancestral mothers.”

I can illustrate this with my own example: I’m Jewish, and the analysis of my genes shows that I belong to mitochondrial haplogroup H7, a subgroup of haplogroup H, itself the most common haplogroup of people of European ancestry living today, be they Jewish or not.

Meanwhile, the situation is completely different when one considers the Y chromosome, which is inherited exclusively by men, and exclusively from their fathers (women don’t have a Y chromosome, as this is the defining chromosome for males).

Well, in 2000, Michael Hammer, at the University of Arizona, showed that the Y chromosome of Jewish men seems to have come down from a very small number of middle-eastern “founding fathers”, different from those of other populations.

Golsdtein’s theory actually explains the double genetic state of affairs configured by the unspecific characterisctics of mitochondrial DNA and the very specific ones of the Y chromosome.

His theory, as an article in The New York Times explained a few months back, is that European Jewish communities were in fact founded by Jewish men who migrated to Europe from the Middle-East and then married local women. These women weren’t Jewish to begin with: they converted to Judaism as they got married.

The Mosaic Law has thus been overturned by the laws of genetics.

P.S.:
However, in 2006, a team led by Doron Behar, of Rambam Medical Center in Haifa, Israel, discovered – once again, through the genetic study of mitochondrial DNA – 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. For those Jews, maybe the Mosaic Law still makes some sense.

Anyway, the bottom line is that part of the fist Jews who migrated to the European continent moved from the Middle-East to Europe with their whole family, while others travelled alone and founded a family in loco. Which, far from being unusual, is after all very much your garden-variety immigrant story.

Image: Study for The Great Jewish Bride (credit: Endless Forms Most Beautiful/Flickr)

I've been nominated, now you can vote for me!

It is with great pleasure that I can announce that my post , Journey to my genes, has been nominated for the 3 Quarks Daily 2009 Science Prize. Thanks to all those who made this possible!

Now it’s time to vote, which you can do here. Just select My Genes and Me: Journey to My Genes from the list and then click Vote at the bottom of the list.

Final results will be announced on the 3quarksdaily.com website on June 8th. The winners, on June 21st.

Vote for your favorite science blog (this one!)

3quarksdaily.com, a website whose editors “present interesting items from around the web on a daily basis, in the areas of science, design, literature, current affairs, art, and anything else [they] deem inherently fascinating”, has launched its first of four annual best blog prizes. This maiden edition of the award, The 3QD Prize in Science 2009, purports in fact to elect the best entry in a science blog.

Nominations will remain open until June 1st. If you wish to nominate a blog entry, all you have to do is go to the bottom of this page and post a comment containing (in the body of the comment) the URL of your favourite blog entry, with or without some brief accompanying remarks about what motivated your choice.

After the end of the nomination period, everyone will have the opportunity to vote on their favorite.

Timeline:
- June 1st, 2009: The nominating process will end at midnight (NYC time) of this date (so there are very few days left to participate in this phase of the process!). At some point on this day, the public voting will be opened.
- June 8th, 2009: Public voting ends at midnight (NYC time).
- June 21st, 2009: The winners are announced.

Other practical infos, gleaned from the 3QD website:
- Anything written between May 24th 2008 and now is eligible for nomination.
- Between June 8th and June 21st, Stephen Pinker will select the winning entry from six finalists.

And now the most important part: if you like this blog, YOU can nominate one my posts....

Here's the post I personally recommend

Passage to Brazil

I've always been told, by my mother’s side of the family, that before going to Argentina, her father had emigrated as a child from Russia to Brazil, right at the beginning of the twentieth century, where his own father had “founded” the city of Nova Odessa, in the state of São Paulo. And also that afterwards, due to problems my great-grand-father had had with other immigrants there (the place was then known as the Colonial Nucleus of Nova Odessa), the family had quickly decided to leave Brazil and gone to Argentina, where they finally settled in the village of Basavilbaso, north of Buenos Aires, in the Argentinean province of Entre Rios.

Well, it looks as if that story is actually true, or at least almost true! I just found out, in a book published in 2008 under the title Judeus no Brasil: Estudos e Notas (“Jews of Brazil: Studies and Notes”), by Nachman Falbel, professor at the University of São Paulo, a passage about my great-grand-father himself! I must say I was flabbergasted - and couldn’t help laughing out loud thinking that after all, my family’s oral tradition, which I had never fully beleived (the idea of one of my ancestor being a “founder” of cities in the New World had always seemed a little too much) wasn’t that far from reality.

I don’t know if my great-grand-father was or not “thrown out” of the place by other colons – who, according to the family’s version of events were furious with him because he had promised them idyllic life conditions in Brazil which obviously didn’t come true. But the thing is that the historical account, as told by Nachman Falbel in his book, while clearly more realistic, isn’t that different from the one I was told in my youth.

For one thing, as Nachman Falbel remarks, the first Jewish colons to arrive from Russia to Santos, Brazil, starting in 1905 – and among them seven members of my family – weren’t all farmers: that’s what they had stated as their profession before embarking on the voyage, simply because they wanted to flee their native country and its pogroms.

But they didn’t like being farmers, they knew little about farming – and the hot and damp Brazilian climate didn’t help. Maybe my great-grand-father had actually convinced others to leave Russia with him, telling them they would be able to work at what they knew best – they were typographers, tailors, etc. –, and maybe they really became infuriated, and were preparing to ride him out of town with tar and feathers. I don’t know.

Nachman Falbel describes, in page 218 of his book, the very serious complaint my great-grand-father, Shaia Hassik, presented to the local authorities concerning the fact that his baggage was taking too long to be delivered to him. And the footnote on that same page adds some more salt and pepper to clearly show my great-grand-father’s negative state-of-mind at the time with regard to his new life in Brazil.

Based on information provided by the book about passenger lists of the ships arriving from Southampton, in 1905, I was also able to find online (through findmypast.com), the original embarkation document of the vessel Magdalena – and the exact date of their departure from England: April 21st.

This confirms that my family was in fact part of the very first group of Russian Jewish immigrants to arrive, at the beginning of May, at the Nova Odessa colony, which had officially just been founded by the Brazilian authorities – precisely on that month of April. So, even though my great-grand-father wasn’t “the founder” of Nova Odessa, he was after all one of its true founders…

Image credit: The National Archives, UK

Spittle

Today, for the first time in more than two weeks, I have some time to spend on this page. These last few days, I’ve dedicated myself full-time to writing and publishing news stories in PÚBLICO about other genes – namely, those the new flu virus.

It’s amazing how such a tiny genome as that, made of just a few genes, can be so hard to dissect and comprehend. But in fact, it’s fairly easy to understand why: the virus changes from one person to another – and to find out, for instance, where it came from, you have to construct its genetic evolution tree taking into account an ever-growing number of infected people. It’s is a different kind of “personal genomics” - but one which becomes extremely important in pre-pandemic circumstances such as those we are experiencing right now.

Let’s go back to my genes. The Spittoon, 23andme’s blog, which I have already mentioned, includes in its SNPWatch section very up-to-date reports on studies involving (reduced or increased) genetic risks links to disease as they are published in the major scientific journals around the world. Here is some of the more momentous “spittle” of the last weeks – which I have of course been comparing to the raw data from my own DNA.

These potential relationships between a given point mutation (or SNP) and a given disease haven’t been confirmed – and for the most part, they only represent slight deviations from the normal risk level for the general population. Nevertheless, they can give you an idea of the feeling you get when it’s not just some anonymous person’s SNPs you’re looking at – but your very own. Some excerpts from SNPWatch:

1 – New England Journal of Medicine (April 15)
Combined analysis of data from Caucasian study participants from the United States and the Netherlands revealed that the A version of [the SNP bearing the code name] rs12425791 is associated with a 1.29 times increased risk of ischemic stroke.

At the end of the article there’s a direct link to the pair of DNA “letters”, or bases (one inherited from my mother and the other from my father) that make up my own rs12425791 SNP. I click on the link, and go directly to my data at that position. They turn out to be: AG.

2– Nature (SNPWatch, April 28)
[The team] found several SNPs associated with autism. All were located in a region of DNA between two genes, CDH9 and CDH10, which encode proteins called cadherins. “These molecules are expressed on the cell surfaces of neurons, and they are involved with shaping both the physical structure of the developing brain and the functional connections among different brain regions. Although a particular gene variant may contribute a small risk for an ASD [Autism Spectrum Disorders] in a particular individual, we estimate that the variants we discovered may contribute to as many as 15 percent of ASD cases in a population,” said [one of the team members] in a statement. The strongest signal came from rs4307059 — compared to two copies of a C, each copy of the more common T version increased the odds of autism by 1.19 times.

My own rs4307059: CT. (For those who are wondering what I might conclude from this: I decided that any “autistic spectrum” personality traits I might have in real life I will only share with my image in the mirror.)

3 – Archives of Ophthalmology (April 14)
The researchers found that one SNP in the TGF-β1 gene in particular was associated with high myopia [-8.00 diopters or worse]. Each A at rs4803455 decreased the odds of developing the condition by 0.67 times.

My own rs4803455: AA (Doubly reduced risk? You don’t say! It seems that I don’t qualify for what they consider “high myopia” in the study, since I don’t quite make it to minus 8 diopters, but I’m pretty close to it. So I don’t give much credence to this result.)


4 – Journal of the American Society of Nephrology (May 1)Researchers studied 260 people who had had bypass surgery and found that those who carried an A at both copies of rs4680 went into shock more often compared to those with other genotypes (69% vs. 57% in AG people and 46.6% in GG people). (...) Prolonged shock, lasting more than 48 hours, was also more frequent in people with two As (25% vs. 13% for AG and 6.8% for GG). (...) people with two As at rs4680 also had greater frequency of acute kidney injury. The median hospital stay after bypass surgery was longer for people with two As at rs4680: nine days vs. eight days for AG and seven days for GG.

My own rs4680: AG (Right in the mid-range; could spell trouble, I suppose.)


(Main image credit: net_efekt/Flickr)

Surname

“Ça c’est un nom bien de chez nous!” – That’s a typical Alsatian name! This was the answer given to me some years ago by an Alsatian gentleman, to whom I was speaking on the phone, when I offered to spell “Gerschenfeld”. I was stupefied: for the first time in my life, someone was telling me my surname sounded typical to him.

On the contrary, I’d gotten used – then in France and now also in Portugal – to remarks such as “ouch, what a complicated name!”, or “that’s a foreign name, isn’t it?”. Or even worse, to phonetic deformations of my patronym that go beyond what one might reasonably expect (“Mme Chantapel? I’m calling you about…” – that was the beginning of another unforgettable phone call, also in French).

For those who have always known their surnames were “typical” of some place, wherever that might be, my reaction may seem strange. But believe me: I was utterly surprised and delighted by that (immediately) nice Alsatian man’s reaction. My name, I realized, might be from somewhere after all…

Five years after his death in Paris, my father’s memoirs have just been published by Libros del Zorzal Editions, under the title Autobombo (which means something like “showing off”), in Argentina, where he had emigrated from Poland with his family when he was only six months old. And as I reread the book, I discovered a historical explanation for the spontaneous familiarity that gentleman from Alsatia had expressed with regard to surnames like mine.

My paternal and maternal surnames [Gerschenfeld and Rosenblatt], my father writes, make me think that my family came from Alsatia or Rhenany, were Jews had settled in the fourteenth century, after their exclusion from France and England. A further series of expulsions forced them to move eastward, to other regions of Germany, and in the fifteenth and sixteenth centuries, they finally settled in what was then the Kingdom of Poland (which also included parts of Ukraine).
At that time, Jews were not allowed to reside in the Empire of the Tsars, but after several partitions of the Kingdom of Poland, between 1772 and 1795, more than 70 percent of that kingdom’s territories had been annexed by the Russian Empire. In this way, and since Catherine the Great imposed on them to remain in the so-called “reserved zone” (in Russian, Cherta Osedlosti), those Jews automatically became the discriminated subjects of that empire, which spanned territories that are today part of Poland, Lithuania, Ukraine, Romania, and Belarus.
Pages of the book, written in Spanish, containing this excerpt

So this explains that… And it also explains why, when I looked more closely at the genetic similarity map 23andme had constructed based on the results of my DNA test (which I have already written about in this blog), I realized that, although the “Ukrainians” are, as I already mentioned, the population whose genetic makeup is closest to mine, that map places me, in fact, at the confluence of people from all over Europe – and in particular of Northern Europe, which includes the French and the Germans.

On the other hand, I’m also very close to the Austrians – and, from Southern Europe, to the Italians –, which suggests that my ancestor’s trail, maybe before the end of the Middle Ages, may have been even more tortuous.

Credit for the photograph appearing on the book's cover: Mario Muchnik

Uncertainties

Is knowing the genetic mutations that lurk at certain locations of our DNA really useful in terms of assessing our risks with respect to diseases like diabetes or stroke?

Some specialists have lately voiced their doubts about this, countering the idea – which has been dogma these last years – that each common disease is the product of a few common genetic variants. This assumption has motivated dozens of so-called “genome-wide studies”, where geneticists set out to hunt down disease-causing genes through the detection of sets of point mutations – the famous SNPs – that would be frequently present in sick people but not in healthy people.

The problem with this approach is that such a simple situation is actually the exception, says David Goldstein, a geneticist at Duke University, who a few days ago commented on the subject in the New England Journal of Medicine. On the contrary, according to him, the most likely is that in their great majority, common diseases are caused by a myriad of rare mutations that, in a given person combine, as in a genetic lottery, to produce a specific disease.

If that is correct, getting a personal genetic test done by firms such as 23andme – which I did myself – or others is practically useless in terms of finding out our disease risks. The tests those businesses offer are merely a reading of half a million (sometimes a bit more) locations in the DNA molecule near which it has been inferred, from genome-wide studies, that one of those common disease-causing mutations may lie. This means that, in most cases, the results will never let us see the big picture. Better, then, to trust our family history of disease to tell us what to expect – the good, old “clinical history”, so dear to physicians a century ago.

According to Steve Jones, a well-known geneticist at University College London, writing today in the Daily Telegraph, those who order commercial genetic tests are simply throwing their money out the window. Goldstein, for his part, also argues that, if we really want to dig out the true and complex roots of human disease, rather than decoding many little bits of DNA from many people it might be better, from the point of view of medical research, to read the whole DNA sequences – the whole two times three billion letters – of a smaller number of individuals.

But not all the news is bad: up to now, nobody has questioned commercial personal genetic tests from the perspective of genealogy – and by the way, Goldstein is a big experts in that field. In fact, as I see it, that part is much more fun and exciting; I never doubted it and I intend to keep digging.

Allergies

I clearly belong, on my father’s side, to a family of allergic people. Happily for me, I haven’t suffered much from it (I’m allergic to drugs such as penicillin and little else, as far as I’m aware, notwithstanding the occasional itchy skin for reasons unknown). But the men in my family tell a whole different story. I remember, as a child, seeing my father’s hands full of eczema plaques (atopic dermatitis) between his fingers, which he was often scratching. This was due, he explained to us, to the fact that the reagents he used in his lab (he was a biologist), triggered allergic reactions. My brother and his sons have had more serious cases of it all through their lives. The most famous victim of this ailment appears to have been the French painter Paul Gauguin.
This morning, I received confirmation that this disposition for eczema is in fact in our genes. The Spittoon, 23andme’s blog, refers to an article published earlier this month in Nature Genetics which suggests that, although having a clear environmental component, eczema is also genetic. The study concludes that 13 percent of Europeans have a letter T at position 75978964 of their DNA sequence of both their 11th chromosomes (each inherited from one of their parents) – and that this multiplies by 1.46 their odds of getting eczema compared to the general population. I looked up my DNA bases at that precise location and found out I’m… TT. Bingo!
This may not be a very big risk – and maybe that’s why I didn’t get it myself. But another article mentioned in that same Spittoon post mentions that the very same configuration, at the same position in the same chromosome, also raises the risk for contracting Crohn’s disease, an chronic auto-immune inflammation of the bowel. For which I discovered, when I had my genes tested, that my risks are three times higher than average. It seems as though the pieces of the puzzle are starting to click into place.

Sharing

One of the most thrilling things you can do with your genetic test results from 23andme is sharing the information with others, in search of unknown relatives. This is how it’s done: when we find someone, for example through a website forum, that we are curious about comparing our genes with, we simply send that person an invitation and wait for an answer.

Almost everybody is willing to share at the “basic” level, that is, as long as no specific DNA details are revealed, namely in terms of disease risks. Even so, it took some effort on my part to start sharing with people I don’t know, but once I understood that my privacy was not at stake, I quickly became addicted. Currently, I already have 17 “friends” in this genetic social network, each and every one of them an absolute stranger, that I invited or who invited me to share.

Once the sharing principle is accepted by both parts, it becomes possible to compare genomes through a functionality called “family inheritance”, that allows both persons to see if there are coinciding pieces of DNA in their respective chromosomes.

In fact, this option is supposed to be used to compare genes among family members, who know from the start that they share big chunks of DNA. And, from what I’ve read, it’s pretty unlikely to find this type of genetic coincidence, by chance, in people we’ve never heard of before.

So imagine my amazement when I found out that 4 out of my 17 “friends” are probably distant relatives, distant “cousins” of mine! It’s hard to believe, but that’s how it is: when I compared my genome-wide genetic data with the data from those 4 people, I discovered that whole segments of certain chromosomes suddenly turned blue on the diagram. In one case, the coincidence spans a sequence of 20 million DNA “letters”, or bases, on chromosome 5. In another, as the image shows, the coincidence involves a 10 million-base sequence on chromosome 4 (I’ve hidden the person’s name for obvious privacy reasons).


What does this mean? It means that, according to the partial genetic results we both received, we both inherited, from one of our parents (either our mother or our father), an identical chunk of some chromosome. In other words, we our DNA present a so-called “half-identical” match (i.e., contributed by only one of our parents). Which, in turn, means that our mother and the other person’s father (or whichever combination is responsible for the coincidence) shared (still share) half-identical chunks of their own DNA too. That is, they also were (are) distant (though slightly less distant) “cousins”. And so on, right back to a common ancestor who probably lived a few centuries ago.

Here is the answer I got from another one of my “cousins”, with whom I share a half-identical DNA sequence 10 million-bases-long on chromosome 9, when I voiced my doubts about such a conclusion: “Yes, it means that we definitely share a common ancestor. The precise point in time may be 300-400 years ago, depending on the rate of recombination in that region. It is unlikely that the common ancestor would be further back than 300-400 years, because recombination would have eliminated it from our common ancestry.” Seems reasonable enough to me.

I also asked a scientist I know who specializes in genetic ancestry and she confirmed.

Apparently, such a state of affairs is not that uncommon in those human communities, namely religious, where people didn’t marry much outside of their group – and which, at some point, became part of a Diaspora, spreading worldwide because of political and religious contingencies that arose in their home-countries.

A4793G

This is the codename of the point-mutation, in my mitochondrial DNA, which signals that I belong to the maternal haplogroup (or matrilineal line) known as H7. It means that, at the 4793rd position in my mitochondrial DNA (hightlighted in purple on the image below), instead of having a letter A (the DNA base, or building block, called adenine), my sequence contains another base, namely a guanine (or G). But that’s not the only ancestry-defining point-mutation which is present in my mitochondrial DNA, for it obviously also contains the series of mutations that accumulated, generation after generation, in my maternal ancestors’ genes since the so-called mitochondrial Eve (the mother of all modern human beings, who, experts agree, lived in Africa around 200,000 years ago) walked on this planet.



At 23andme, they tell me that the sequence of the point-mutations which, starting with A4793G (4793 for short) and travelling back in time, go from haplogroup H7 back to mitochondrial Eve, is as follows: 4793, 2706, 7028, 11719, 12705, 10398, 10873, 15301, 8701, 9540, 1018, 769, 13650, 16278, 3594, 4104, 7256, 7521, 10810, 15301, 16129, 16187, 16189, 825, 8655, 2758, 2885, 7146, 8468, 16230, 11914, 10589, 6185, 4312. (A soupful of numbers indeed!) Mutations at positions 2706 and 7028, for instance, define haplogroup H, of which H7 is a direct sub-haplogroup. Thus, going down the tree from the branches to the trunk, one goes through a series of increasingly ancient haplogroups: HV, R, N, L3, L2, L1, and on back to that single, primordial mother.

I want more!

I would really like to have the whole of my mitochondrial DNA sequenced (this is the part of our genome that tells us about our direct matrilineal descent). The best website for this seems to be Family Tree DNA. But out of the three sequencing options they offer – mtDNA, mtDNAPlus, and mtFullSequence –, the only one I’m interested in, because it would give me more information than what I’ve already got from 23andme, is the third one – and currently, that costs 495 dollars. I’m still pondering.

Both the other options would give me much less information than what I already have, and, accordingly, a lower resolution on my maternal “haplogroup” (genetic family). The first option (129 dollars) only reads 22 SNPs (point mutations) in the so-called Hipervariable Region 1 (HVR1), which is like looking at the mtDNA with a simple magnifying glass; the second one (189 dollars), adds to that a series of SNPs from Hipervariable Region 2 (HVR2), which gives a somewhat higher resolution. But compare this to the data from 23andme, which reads some 3,000 SNPs not only from HVR1 and 2, but also along the rest of the whole mtDNA molecule. I rest my case. The advantage of FTDNA, though, is that it’s been around longer and has many more clients than 23andme, which means many more people with whom to compare our results in search of similarities.

Chromosome painting

Here is a view of my chromosomes 1 through 22 (actually, each bar represents the two copies of each of my chromosome, one inherited from my father and the other from my mother). There are two more chromosomes (the 23rd pair), which are not drawn here, and which determine the person’s sex. In my case, since I’m a woman, I got an X chromosome from each of my parents and I am XX.

This functionality of the 23andme website, called “ancestry painting”, allows me to see the origin of my chromosomes in terms of large geographical regions.




In my case, the image shows that 99 percent of my chromosomes 1 through 22 are of European origin (they are painted black). The rest of my genome, less than 1 percent, is painted orange and is of Asiatic origin. This encompasses a small fragment on chromosome 8 (inherited from just one of my parents, as seen from the fact that only the lower half of that fragment is painted orange); and a slightly larger fragment on chromosome 18, that seems to have derived from the same geographic origin in both my parents, as it is completely painted orange. Chromosome painting has another very interesting application, which I will explain on some other occasion.

Origins

For the sake of consistency in calculating the estimates of our risk for this or that disease, one of the things we need to define at the 23andme website is our “ethnicity” – which simply means, actually, that we have to specify the geographical origins of those of our ancestors whom we know of. But when I tried to do this for the first time, I didn’t find what I considered to be my appropriate ethnicity, namely Eastern Europe.

My grand-parents all came from the Ukraine, near Odessa, which is clearly Eastern Europe, but I only had the choice between checking a box for Northern Europe or one for Southern Europe. Where was Eastern Europe? Did I have to choose between those two? The closest choice, I seemed to me, was Southern Europe, but that didn’t seem specific enough – not the least because the stories of the Iberian Jews (Sephardic) and the Jews from Central and Eastern Europe (Ashkenazi) are pretty different. The short reply to yet another email to 23andme was: “You can use Southern Europe as the option”. OK; so that’s what I did.

I must say that I was pleased to learn afterwards that my genes also confirmed my own, unlisted, first choice. Using a functionality called “global similarity – advanced view”, I was able to see that the group I was closest to in terms of genetic similarity were the “Ukrainians” – and that they were placed, adequately, between Southern… and Eastern Europe (I’m the larger green plot on the maps below).

Things evolve very quickly!

While I was waiting for my results, I had the opportunity to take a look at the kind of results I would be getting. The 23andme website allows you to create a user account right away and to explore the genes of a fictitious family, the Mendels (the name is obviously a discreet homage to Gregor Mendel, considered to be the father of genetics).

One of several questions I asked myself at the time concerned the fact that, apparently, they weren’t going to test for mutations in the BRCA1 and BRCA2 genes. But it so happens that mutations in those genes mean a high risk for breast cancer. I sent them an email asking about it and this was the answer I got: “In the future we hope to include additional analyses that will identify some of the most common breast cancer-associated BRCA mutations.”

The future was actually right there and then, except I didn’t know it until a few weeks later, when I got my results, which included the analysis of three possible mutations in those (in)famous genes. But I didn’t realize that right away. I opened the webpage which contained my results on those genes and only then did I start to grasp the significance of what I was looking at. It was really scary because I was confident – since the future is supposed to lay in the future, not in the present – that those were not the genes I had asked 23andme about. They were. Happily, I don’t carry any of those three mutations.





But the mere fact of not being a carrier doesn’t mean that I don’t carry any other of the countless mutations that can affect these genes. As they had also explained in that reply email, what I got isn’t a diagnostic test of my real risk for hereditary breast cancer. For that, I would have to get the full sequence of those genes, which means they would have to read all the letters in it, and identify every possible mutation. 23andme doesn’t perform this kind of sequencing.

Journey to my genes

(click on the title to read the whole text)
View PDF of the print story (in Portuguese)


The ideia of learning about the secrets of my DNA has fascinated me for years. Not so much because I want to know about my predisposition to this or that disease, but for what my genes could tell me about my deep ancestors’ origins. Recently, the price of these genetic tests became affordable enough for anyone to have access to them (for a few hundred euros) and I struck the following bargain with my editors at my newspaper: if they paid for the tests, I would write about what they revealed – the good things, the bad things and the so-so things. Here they are. Welcome to me!



The instructions tell me to spit into the little plastic tube. It’s 10 a.m. on a December morning. In the bathroom, I open the test tube and start spitting into it. I haven’t eaten or drunk anything over the last half-hour, I haven’t brushed my teeth either (more instructions). I can’t get this wrong, it has to work without a glitch.

Contrary to what one might expect, it’s not easy to fill with more than an inch of spit a small tube about a half-inch in diameter, while “trying not to make bubbles”, as the instructions go. To facilitate the process, they tell us to wag our tongue against the inside wall of our cheeks. This ensures that together with our saliva, cells from the lining of our mouth will also fall into the test tube. These are the cells that contain the DNA that is going to be analyzed.

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I do this over and over again. It seems my mouth is getting drier and drier, but it’s just a feeling: the spit slowly fills the tube until it reaches a mark for the desired amount. I’m not really spitting, it’s more like drooling in a very controlled fashion. I look at my watch: I’ve been at it for almost 15 minutes.

I close the tube with a large cap, a special cap that leaks a buffer solution into the saliva sample when you screw it on, to preserve it. I shake the whole thing vigourously, unscrew the large cap and screw on another one, a smaller, normal, final cap. Done. I slip the test tube into a padded envelope, addressed to somewhere in California, that I will dispatch by special mail later in the day.

I ordered this genetic test kit online, in the beginning of December, at the 23andme.com site. A few days later, I received, by special mail, a glossy little green box with my name and surname clearly written on it in capital letters, along with a code number (claim code) that would give me access to my results when they were ready. It was inside the box that I found the test tube, the two caps and the list of instructions.


Genes with a name and a surname

23and me is one of several businesses that currently offer to analize their individual DNA to the public at large. It’s one of the best-known and also one of the most serious. Equally attractive is the fact that they drastically cut their prices at the end of last year. For just 399 dollars, they provide not only a guided tour of our chromosomes, in search of the hidden secrets of our DNA – mostly disease risks (brrrr!) –, but also a description of a series of physical and psychological attributes and even a glimpse of our ancestors. For the first time, it's become possible to obtain information on our own DNA, a DNA with our name and surname, and not just the DNA of an anonymous representative of the Homo sapiens sapiens species.

It doesn’t mean they read our genome’s full sequence – that is still out of monetary reach of the great majority of us. Instead, they only read a (tiny) part of the six billion letters or bases that make up our DNA (half of them inherited from our mother and the other half from our father, joining in pairs on our chromosomes).

This more modest alternative consists in detecting bits which are only one DNA-letter-long, so-called SNPs (single nucleotide polymorphims, pronounced snips), and which may harbor point mutations. When a snip is located in the middle of a gene, it alters its function; but even when that snip doesn’t affect any gene, the fact that is is mutated can suggest that, close by, there is a significant mutation (significant in terms of our health, for instance) on some yet-to-be identified gene. In this latter case, the snip acts as a marker, as a signpost and can contribute to the identification of important genetic mutations. “The SNP is then useful as a landmark, similar to how people describe locations”, explains 23andme on their site. “You may not know where the local hardware store is, but if you know it’s within a block of the pharmacy you went to the other day, you will be able to find it.” It is estimated that the human genome contains about 10 million SNP, and at 23andme they read 550 thousand of those from our cells, wisely distributed along all the chromosomes.

The main aim, says 23andme, is to inform people about their health risks, because that information – which could lead to life-style changes on our part and even make us more alert with respect to certain disease symptoms – is a new form of empowerment, of control we have over our own life.

My motivation, though, was somewhat different: the idea of knowing my DNA, of looking at my A, T, G; C sequences had fascinated me for years. I imagined it would reveal fascinating things about my ancestors. I was never very interested in my recent genealogy, but genetic genealogy, the possibility to discover my roots at the scale of thousands of years, that seemed to me to be worth the trouble. And if in so doing I also managed to link that genetic information to historical data about my more recente ancestors, so much the better.

So that is why, when the opportunity presented itself to become a guinea-pig in these experiments in “personal genomics” (that’s how they call this new field), I couldn’t resist it. Of course, I pondered the risk of discovering terrible things about myself in the way of inheritable diseases, biological deficiencies or the like, against which I would be powerless. Would it be better to know or not to know my risk for breast cancer? But curiosity had the better of me. And that’s how I ended up spitting into that little tube.


Moment of truth

I received my results almost two months later in the form of an email: “Congratulations! Data for the person listed above are now available on the 23andMe website.” And then, a reminder of my login name and a link, and another link for the Getting Started Guide…

I entered my user and my password, ready to face the results without hesitating. But I must confess that I felt somewhat like I had when, some years earlier, I had gotten the results of an HIV test my bank had required for a loan to buy a house: pretty scared, even though I knew the odds of getting a bad verdict were very slim. And so, just as I had done on that occasion, I also asked my husband to stay at my side and hold my hand…

"Welcome to you" was the first thing I read when I accessed my personal page. Underneath that sentence, several sections: My Health and Traits, a survey section, and another one titled “global similarity”. Where were my results? Where were my genes? My list of diseases? My ancestral origins? At first sight, it was all pretty confusing. I started by looking at my “raw data” – that is, at the sequences of my DNA letters that had been decoded –, and I soon discovered that they made, to say the least, for indigestive reading. There were lists and lists of thousands of numbers, letters, gene names, links to incomprehensible genetic databases, comparisons with “reference sequences” (whatever those were) I had never heard about before.

I went back to the initial page and, determined to deal first with the issue of disease, I clicked on the My Health and Traits link. One of the first things I had to do there was to decide if I wanted to see (opt-in) the results concerning a type of a hereditary breast cancer. I was a little nervous with the whole situation, imagining what terrifying, unavoidable things I was about to find out, so I made a hasty decision when I should have pondered more carefully: I happily clicked on the opt-in button, confirming that yes, I wanted to see the results. I quickly scanned the new page to the bottom – and only then did I realize what it was all about.

It so happens that these results concern mutations that can affect to sadly famous genes, called BCRA1 and BCRA2. These genes, although they are responsible for only 2 percent of breast cancers, dramatically increase, in their carriers, the probability to develop breast (and ovary) cancer – to about 50 to 80 percent. At this level of risk, it is difficult to tell it apart from absolute certainty. Moreover, as I read on that same page, in Ashkenazi Jews (a group to which I belong), those mutations are responsible for 80 to 90 percent of hereditary breast and ovary cancers. Luckily, I don’t carry any of the three mutations that 23andme test for. But after the fact, I got cold sweats: what would I have felt if the verdict had been different? How do you live with a thing like that hanging over your head?


Diseases by the dozen

I also found out that I have increased risks (but not certainties, here things are not so harsh) for two other diseases: three times more (1.4 percent) than average to get Crohn Disease (an autoimmune, chronic inflammation of the bowel) and almost twice the risk (2,3 percent) of getting type 1 diabetes (caused by the destruction of insulin-producing cells in the pancreas). The first disease has a hereditary component of 50 to 60 percent; the second one, of 72 to 88 percent. Curiously, as far as I know, I don’t have a family history for either of them. But from now on, I’ll have to be on the lookout for symptoms – and talk to my doctor to see if there’s anything I can do in terms of prevention.

My report contains 102 items – for diseases, serious mutations, physical traits and others. In some cases, the relevance of the SNPs which were analyzed has been largely confirmed by research, but the impact of the mutations is not so strong. In other cases, there is still no scientific consensus on the relevance of the corresponding SNPs. A lot of the information they give us is based on preliminary results. But even so, the results are dully presented and submitted to our consideration. There are links to the most recent scientific papers on each subject – which are not always enlightening, since their conclusions are frequently in contradiction with each other. But there’s no doubt about the fact that it’s all neatly done.

A quick overview: I have more than average risks for a series of cancers, average risks for others, and less than average risks for others. Who doesn’t? Luckily, I don’t seem to be a candidate for multiple sclerosis, a disease for which the genetic component is rather strong (24 to 86 percent).

My risk for having a heart attack (which may have a hereditary component of up to 52 percent) is average. Needless to say, having an “average risk” can be pretty uncomfortable all the same, if that average risk is high… And, for heart attacks, it’s around 20 percent. Even worse is the fact that for obesity, where my risk is also average, that risk is… 60 percent (in the American population). To sum up: everything is relative. But it is also clear that my risks are also affected by my life-style, my diet, etc. – and the good side is that I have ways at my disposal to minimize those risks.


Brown eyes

Concerning my physical traits, I learned that I “probably have brown eyes”. In fact, they’re green. My father had brown eyes, but not me, I’m sure of that. Nevertheless, green appears, in my report, as third choice for eye color, following brown and blue. When I saw the result, I said to myself: “If they don’t get it right for eye color, should I trust the rest?” But the fact is, as they explain on that same page, that in spite of being almost totally inherited, eye color is controlled by a whole bunch of genes. That means that the genetics of eye color is very complex and most of the genes involved are still unknown. Another surprise was discovering that my genes dictate that it is likely that I don’t have many freckles or moles. I couldn’t help laughing – I have a lot of freckles and moles. But the fact is that skin complexion and eye color are related, so it’s not surprising they also got that wrong.

Anyway, my genes and I agree on other things: they tell me I’m lactose-intolerant (and it’s true that drinking milk makes me nauseous); that I’m susceptible to viral gastroenteritis (as I know by experience); that my earwax is wet (right!); that I don’t flush when I drink alcohol (right!). On the other hand, they also inform me that I shouldn’t like the bitter taste of broccoli or of unsugared coffee – but I do; that I’m not immune to HIV or malaria (I hope never to have the opportunity to confirm this); that I have sprinter’s muscles (maybe I should take up jogging… but I probably won’t). One last result – and here I trust genetics: I don’t carry the mutation for cystic fibrosis, a very serious genetic disease. This information is important, because carriers, even if they don’t have the disease themselves, can transmit it to their offspring.

There is still room, in this long list, for a series of cognitive attributes, such as “measures of intelligence” (it seems I’m smart!); memory (it seems I have a good memory!). They also tell me I am capable of learning from experience. But here, we are obviously treading a very unsteady terrain.


Genetic roots

As I already explained, my main motivation, when I ordered the kit, was to find out something about my ancestors – or rather, about my maternal descent. Being a woman, I didn’t inherit my father’s Y chromosome and so my DNA cannot give me unequivocal information about my paternal descent. To achieve that, I would have to have my brother or one of his sons test their own DNA – or at least their Y – but that’s another story.

In order to determine my "matrilineal inheritance”, at 23andme they analized my “mitochondrial DNA”, a part of my genetic makeup that isn’t found inside cell nuclei like the rest, but rather inside cellular organelles called mitochondria, which are the cells’ batteries. These are transmitted, unaltered, by mothers to their sons and daughters, inside the egg’s “white”. Contrary to what happens with the rest of the genome – where half the information comes from the father through the spermatozoid and the other half from the mother through the egg "yolk" – the mitochondria and their set of genes come exclusively from the mother.

Mitochondrial DNA, which contains around 16,000 base pairs, was given to our mother by her mother, and to her mother by her grand-mother, and so on. As time and generations pass, that little bit of DNA mutates with a frequency that is more or less known. That’s why it's been used by geneticists as a “molecular clock”, to go back in time (and space) to the so-called “mitochondrial Eve”, the mother of all modern human beings. Thanks to the study of mitochondrial DNA, it is today widely accepted that that primordial woman lived in Africa some 200,000 years ago.

Every time a new mutation arises in a woman’s mitochondrial DNA, and that “founding mother” passes it on to her children, that gives rise, in theory, to a new motherline. But not all those lines survive: only some of those genetic families – or “haplogroups”, as experts call them – survived to the present day in the genes of the different peoples of the world. And by comparing the different mitochondrial DNA lineages which exist in current populations, it is possible for scientists to go back in time and space to approximately determine the temporal and geographical origin of different haplogroups and reconstruct the path of human migrations through the millennia.

At 23andme, they read some 3,000 SNPs distributed along the whole sequence of the mitochondrial DNA to determine a person’s haplogroup – his or her family by matrilineal descent. Sometimes, the haplogroup assignment can be combined with historical data to provide information about the possible whereabouts of someone’s ancestors a mere one or two thousand years ago.


Genealogical disappointment

However, as it turned out, my haplogroup, called H7, seems to be very rare (which simply means, I suppose, that not enough people belonging to that haplogroup have had their mitochondrial DNA tested yet). Because of this, the geographical origin and the age of my haplogroup are still pretty vague.

I must confess I felt pretty disappointed. I had imagined that I would find out how and where and when that early founding mother of which I am a direct descendant might have lived. But it wasn’t to be so. Pity.

Meanwhile, during the last few weeks, I have consulted a series of online community discussions at 23andme, I’ve performed Google searches, I’ve written emails to several people. I discovered that there were ways to compare my mitochondrial genes to those of others, but I haven’t been able to actually do that yet. I joined a Yahoo! mailing list of people who are also H7, but some of the information I got through that channel seems to contradict other informations I gleaned from other websites.

What I know, for the time being, is that haplogroup H7 is an offshoot of another haplogroup, H, which is today the most common haplogroup in Europe and which, according to 23andme, originated in the Middle East around 35,000 years ago. Then, 25,000 years ago, it spread across Europe. Several thousand years later, at the peak of the last glaciation, or Last Glacial Maximum, those men and women were forced to take refuge in the more temperate regions of the continent – the Iberian Peninsula, Italy, the Caucasus. What happened next is suggested by several studies – one of them by António Amorim and his team at IPATIMUP (Institute of Molecular Pathology and Immunology), at the University of Porto, Portugal: when the ice started regressing, about 15,000 years ago, the members of haplogroup H may have started to reconquer Europe, giving rise, after several later tribulations, to different sub-haplogroups, among which H7.


A soupful of letters?

Another thing I found out about my genes’ “geography” (and not only the mitochondrial set) is that, although more that 99 percent of my chromosomes denote a European origin, a small portion, less than 1 percent, comes from Asia. I'm really curious about the specific geographical origin of that tiny bit of DNA from another continent…

I was also able to confirm, thanks to a very interesting functionality at the 23andme website – the so-called “global similarity” announced in the welcome page – that on a global level, the population my chromosomes seem to be closest to is centered on the Ukraine. This doesn’t surprise me, as it is precisely from the Ukraine that both sides of my family, both maternal and paternal, come.

However, one could object that, overall, I don’t know now much more than I already knew. After all, just by looking at the life story of my parents, grand-parents and so on, I manage to get a pretty good idea of the inheritable pathologies that might threaten me in the course of my own life; I don’t need a genetic profile for that. And neither do I need to know my genes to know that it’s better to lead a healthy, active life and all that. Regarding my origins, they remain as obscure – or as clear – as they were before. Ultimately, the data I obtained is merely a gigantic soupful of letters.

But that’s not exactly the way things are; this state of affairs is not fixed. As new, credible information comes along about other SNPs among the 550 million that were analized, 23andme will quickly update my profile to include them. The service we pay for includes updates of the interpretation of our data in the light of the most recent scientific results. What I can ask, instead, is what I’ll do when they offer to let their clients know, as they’ve already announced they would, about their risk for Alzheimer’s disease. I still don’t know what I’ll do. What I do know is that, in spite of the obvious limitations of this new science, I’m still as fascinated by what I imagine my genetic data might tell me in the future. And that’s like embarking on a new adventure each day.