Turns out I am genetically British and not Gallish!

On January 28th 2014, I became a British citizen (while still retaining my original French citizenship). This blog post is not about the reasons behind that decision, that I might or might not expose someday. But I just discovered that I might already be British by descent!

A year ago, I sent some spit to a US company called 23andMe. This company amplified my DNA and looked for all the sites that are variable in the human population (e.g. some people present at a given position on a chromosome the base pair G-C while other have the base pair A-T). We called those SNPs (for Single Nucleotide Polymorphisms, pronounce “snips”), and the procedure SNP genotyping. My aim was to look for increased risks for some diseases. If we have the genotype (the state of all the SNPs) of many people, patients and controls, one can determine if some SNPs are statistically more frequent in people with a disease than in the general population. I thus discovered that I had a higher risk than the general population of having Venous Thromboembolism, Alzheimer’s Disease and Exfoliation Glaucoma. Conversely I have a lower risk of Gout, Colorectal Cancer and Age-related Macular Degeneration (so less chance of becoming blind with macular degeneration but more with glaucoma, hmm). I have also a higher sensitivity to the blood thinner warfarin and a decreased sensitivity to treatments for type II diabetes and hepatitis C. This health related activity of 23andMe was recently blocked by the Food and Drug Administration, a decision that led to many interesting and heated discussions (google “23andMe” “FDA” to have an idea of the divide that decision brought to the community of biologists).

However, there is another use of SNP genotyping: genealogy. Because mutations are very rare, most SNPs tend to be conserved between parents and children. As a result, I share around 50% of my SNPs with each of my parents and my children (49.9% with my daughter who was also 23andMeed), 25% with my grand-parents etc. We have a lot of SNPs, several millions. That means we can trace genealogical relationships very far. If we know the geographical localisation of the 23andMe clients, and assume most of them did not travel away from where their ancestors lived, one can use the genotyping to follow genetic migrations.

23andMe offers tools to do just that, and surprise … I am mainly of British ancestry! One talks here of the ancient ancestry, before fast travels and genetic mixing. 23andMe provides three levels of statistical analysis, from the most conservative (less informative, but more robust) to the most speculative (more informative but less solid).

ChromosomeViewConservative

ChromosomeViewStandard

ChromosomeViewSpeculative

Whatever level of significance, what stands out is “British & Irish”. Another tool allow to visualise this DNA ancestry on a global Similarity Map.

GenotypingMap

Each square represent a genotype, i.e. a person, significantly related to me. My genotype is represented by a green “callout”. My contacts on 23andMe (people I contacted or who contacted me, because we are perhaps distant relatives) are represented by black callouts. As you can see on the maps, my contacts and I cluster better with the British cloud than the French one.

What could that mean? I can imagine three reasons, with increasing likelihood.

1) Most of British clients of 23andMe are of French ascent. Therefore the apparent result is the opposite of the truth, the cluster labelled “British” being made of French genotypes. This is not completely insane. After all, William the conqueror and his army came from France. However, him and his army were norman, i.e. viking (and since Normandy is close to Britanny, that could rather explain the 1.3% scandinavian).

2) There was a recent influx of British DNA in my ancestry lines. This is certainly possible, but more than 50%? The influx should be recent and multiple (affecting both lines of ancestry). And indeed looking at the standard and speculative mapping above, we see British ancestry on both sets of chromosomes.

3) Some theories postulate that invasions do not affect the general population, only aristocracy being replaced. They received support from genotyping. Principal component analysis of genotypes from a pan-European cohort reproduced the geographical origin of its members. In other words, the genotypic distances followed the geographical distances.

Is-it always true though? Both my parents are “bretons“, coming from Britanny. Britanny was invaded repeatedly between the 3rd and 6th century by britons fleeing picts and anglo-saxons. Some legends state that these britons killed celtic mens and fecundated the women (the same legends state that the women’s tongues were cut so that they could not teach their own dialect to their children). Could it be that in Britanny the genetic pool was genetically replaced?

I would be very interested to hear from any other breton having had their genotype done.

Advertisements

Is genome confidentiality such a big deal?

I recently sent my spit sample to 23andMe in order to be genotyped. I chose the option to share my genotypic information with 23andMe and all its clients (*). This brought me to think a bit about genome privacy, despite not being involved in genomics research myself.

Genome confidentiality seems to be a big deal. For instance the 1000 genome project went into great lengths to completely anonymise the data; and no phenotypic information is provided in order to preclude identification (which seriously limits scientific discoveries possible from the project’s data). It seems that showing your genome is more taboo than showing your winky. Once it is out, it will be used by plenty of oppressors etc. This fear is increased by movies such as, otherwise excellent, Gattaca. The most frequently voiced concern, because the more immediate maybe, is the fear that insurance companies would base their premiums on the genome.

This fear is probably real; insurance companies will try to base their premiums on the genotypes. However, I would argue that 1) much information about your genome is already out there, and insurance companies already use it, 2) use of genome information is perhaps not a completely outrageous idea, and 3) there are other ways than confidentiality to protect us.

Although the relationships between genotype and phenotype are complex, our entire modern understanding of biology is that our phenotype is the expression of our genotype in the environment. Accordingly one can infer much about your genome from your phenotype. You gender, the colour of your skin and hair, the fact that you are obese or not, send signals, more of less ambiguous, about your genome. Your blood type is generally fairly public (in France we carry a “blood ID card”, in case we have an accident). Plenty of other phenotypes can be swallowed by good machine learning algorithms that will infer part of your genotype. Insurance companies already use that. It is more apparent for, e.g., car insurances, for which women pay lower premiums. But each time you fill a form for an health insurance mentioning past illnesses or behaviours, or illnesses of your relatives, you are actually feeding information about your genotype. And insurance companies already use that to alter what they cover.

Now, is it really a problem? Why should private insurance not change premiums based on the genome? They are private companies, and their mission is 1) not go belly up, and 2) make money (whether we are talking of indecent amounts of money is another issue). The situation is very different for national insurances. In this case, everyone pay, proportionally to their income, and everyone is covered no matter what. And people must subscribe to national insurances (BTW, this is why French securite sociale, the NHS, Obamacare etc. are so important. Society cannot function properly without basic national egalitarian systems). But no-one is forced to subscribed to a private insurance. The insurance company then needs to balance between number of clients and premiums. If the premiums become too high because of their genomes, people at risk will not subscribe. And people who are not at risk will also not subscribe … because not at risk, so the company will go down. Companies would also compete, which would bring the price down. Some would also be advertising the fact that they do not take so much account of the genotype etc.

However, it is a controversial issue, and the society at large may decide that insurance companies must not base their premiums using genotyping info. But is genome confidentiality the solution to enforce that? There are laws forbidding the use of some data for discrimination. People cannot be discriminated based on their ethnic origin for instance, or their religion. As such, when they subscribe to a health insurance, they do not need to come to the meeting with a whole body suit. Why would it be different for the genome? If a law says “Insurance companies are not allowed to use genome derived information”, any insurance company caught doing so can be prosecuted and pay lots of money to the relevant customers. As far as I am concerned, I prefer to live in a world where the apples are on display and not locked away in the market, but if an apple is stolen, police try to catch the apple thief.

In the science fiction novel The Light of Other Days, tiny wormholes allow to see in the past. Effectively this allow anyone to spy on everyone … a fraction of second in the past. All privacy is gone. And then humankind reacts in two ways. Half of the humankind freaks out an start living naked in crowded entirely dark houses. The other half realizes that privacy if gone for good and adapts. They grow up.

(*) I did that despite a strong aversive reaction to the recent announcement of a patent deposited by the company covering “Polymorphisms associated with Parkinson’s disease”. The “discovery” (and not the “invention”) was made using the data provided by thousands of clients who paid for being genotyped. The company did not deposit the patent in order to protect the community from exclusive exploitation, but instead to ensure it guarantees a return on investment. The reason advanced is that treatments will only be developed if such a return on investment is sufficient, and not to stiffle innovation or hinder future research. Past history such as Myriad Genetics and the BRCA genes makes me somehow dubious. I will only believe that claim if 23AndMe launches a competitive process to select the company that is the best suited to develop treatment, and gives an exclusive license to this company. But 23AndMe itself should not earn money from that patent.