Tests of DNA ancestry – and its many caveats – explained



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Identical twins have virtually identical DNA. You think that if a group of twins sent a DNA sample for genetic ancestry tests, they would get exactly the same results, right?

Not necessarily, according to a recent research by the Canadian Broadcasting Corporation. In fact, journalists have shown that twins often do not get the same results from a single company. And across the industry, estimates of where an individual's ancestors lived may differ significantly from company to company.

In one example, the 23andMe consumer genetics company told a twin that it was 13% "broadly European". The other twin's test, meanwhile, showed that she was only 3% of European descent. In addition, when the twins had their DNA tested by five different companies, each gave them different results.

A computer biologist told CBC that the differences in results were "mystifying."

So, what explains these differences? Overall, discrepancies in ancestral tests do not mean that genetic science is a fraud and that companies are just making up those numbers. They have more to do with the limitations of science and some key assumptions that companies make when they analyze DNA for ancestry.

Companies that provide proof of ancestry, such as Ancestry.com and 23andMe, provide accurate ancestral DNA analysis of their clients. They can say, for example, that someone's ancestry is 25% Italian, 74% from East Asia and 0.1% from Sardinia. They also market your product in a way that suggests that your test reveals something deeply meaningful about you.

In his accounts of ancestry, 23andMe says that "your DNA tells the story of who you are and how you are connected to populations around the world." MyHeritage, another company that provides ancestry analysis, writes "Our DNA testing offers the powerful experience of finding out what makes you unique and learning where you really come from. "

What is not always obvious in these reports is how they are based on estimates that may vary from company to company and have internal error sources. Companies have Web pages that explain these limitations, but you have to dig a little to find them. You could very easily buy one of these kits without going through it.

The genetic test of consumption is growing explosively. The global industry has already evaluated the genomes of at least 10 million people. By 2021, according to some experts, that figure may be closer to 100 million people. These genetic tests usually cost $ 60 to $ 100 – or more, if they contain health information. As the market grows, consumers need to be aware of what exactly these tests are telling them (and even more when it comes to health and wellness information).

So what does this really mean when a company tells you that you are 40% Greek? To answer this question, it is helpful to understand exactly what these tests are looking for and the assumptions they need to make to guess their ancestry.

"What is important to understand is that genetics can guide the answers" about ancestry, says Joe Pickrell, geneticist and CEO of Gencove, a company that sells genetic testing software and hardware to other companies. "There is no time machine, nor crystal ball."

While genetic ancestry tests provide accurate percentages of our heritage, reports are best thought based on imperfect data.

Step by step, let's walk through why.

First step: spit in a tube

There are about 3 billion base pairs – the individual letter instructions of our genetic code – that make up the human genome. When you spat in a tube and sent it to a company like 23andMe, Ancestry.com or MyHeritage, they did not bother looking at each letter.

That would be an exaggeration.

All humans have about 99.9 percent of their DNA in common. So instead, to speed up the process, the tests look for locations in the genome where people commonly vary from one another.

These are points where you can have the nucleotide (ie, the molecule that forms half a pair of bases) adenine, and I have thymine. That's it. All in all, these small changes in unique letters in our DNA can help explain why one person is taller than the other or why one has brown eyes and another has green.

In science jargon, these variations are called single nucleotide polymorphisms, or SNPs (pronounced "snip"). And companies can analyze half a million or more of them in an ancestry test.

When a genetic testing firm receives a tube of saliva in the mail, it first needs to extract the DNA from it. "You remove cellular debris, proteins, all things that are not DNA," explains Yaniv Erlich, scientific director of the genetic ancestry company MyHeritage. They make copies of your DNA and then divide those bleachers into smaller pieces.

The pieces are then fed into a machine called genotyping matrix. These matrices – and this is an absolute simplification – function as a coin sorter, but for SNPs. They will tell companies which versions of SNPs you have inherited and in which genome location.

Many SNPs are insignificant when it comes to our health. But they can be useful starting points for tracing ancestry. That's because, like everything else in our genome, SNPs are passed down through the generations. The more SNPs we share in common with another person, the more likely we are to share a similar and more recent ancestor. Their ancestry is estimated by comparing their SNP results with a genetic database of people with known ancestors (more on this in the next section).

This is the first source of possible discrepancies in ancestry testing: although these genotyping arrays are extremely accurate, they tend to make small errors.

"We're talking about 99.9% accuracy for these arrays," says Erlich. But even with this high level of accuracy, when you process 1 million places in the genome, you can get 1,000 errors. Only these small mistakes can help explain why one twin can have slightly different results from another. (And this source of error is also the reason why the health outcomes you get from genetic testing companies may also show discrepancies.)

Step Two: Your DNA is compared to the DNA of other people with known ancestors

Leaving aside errors, the genotyping we get from each of the consumer testing companies should be virtually identical to the other (ie, if companies are looking at the same set and number of SNPs). But how companies analyze that raw data varies. And that is why the results of ancestry of one company may seem a little different from the results of another.

See how it works.

Companies like 23andMe, Ancestry.com and MyHeritage compare their set of SNPs to known reference groups (SNPs that tend to be found in people of Greek origin, say). The tests are looking for evidence that you have common ancestors with people in the referral group.

But the reference group that each company uses may be different.

Another limitation: these reference groups are largely based on people who are reporting their ancestors. These people can be sure that they know where their families come from, but it is not a perfect measure.

Ancestral DNA companies can track European DNA in specific countries. But if you are a minority, your report may be more vague. Before this past summer, 23andMe could only equate people to just three major regions of sub-Saharan Africa, which is a huge area with a lot of geographic and ethnic diversity. This is because there are not so many African people in the reference datasets of these companies.

"Imagine you're from a small town in Spain," Pickrell says. "What if [the testing companies] have a lot of people from that small town, they can combine it with them very effectively. "But if they do not have people from that specific small town, they may determine that you are broadly Spanish or European.

Step 3: A computer program has a better hunch on your ancestral makeup

A final step remains: these companies do not just match their ancestors but attribute very specific percentages. Thus, an ancestral DNA test may reveal that you are 23% European, 24% Chinese, and so on.

This is where computer programs come in. "The algorithm says," Let's try to join the ancestors in different combinations, to get a similar variation [of SNPs] that you have, "says Erlich.

You're looking for a better fit, not a perfect match.

And it is imperfect, especially in the differentiation between ancestors that look very similar genetically.

"There is very little [genetic] variation in Europe, "says Erlich, as an example. The people of England, for example, do not look so genetically different from the people of Ireland, he says. So the computer is more likely to make the mistake that a person's ancestors were English (not Irish) than to make the mistake that a person is English (not Taiwanese).

In addition, the programs have to make some assumptions about how far in the past their ancestors lived in a certain place. This is also imperfect, with a range of errors.

Computer programs are also sensitive to the small errors embedded in the genotyping process. And again, the production of the program depends on the reference DNA that the company has in its database.

Remember: DNA ancestry is not the same as inheritance.

Here's another important thing to remember: Ancestral DNA tests do not tell you where each member of your family tree lived. Instead, they tell you how much of the DNA you inherited.

That's why siblings can get different reports of DNA ancestry services (even if they share exactly the same relatives). "It's possible your brother inherited a piece of DNA from one of your ancestors that you did not inherit," Pickrell says.

Remember that you inherit half of your DNA from your mother and half your DNA from your father. But your father may not pass on to you all the genes he inherited, for example the Sardinian side of his family.

As you move back and forth in time in your family tree, "there is some possibility that you have not inherited DNA from one of your ancestors," Pickrell says. Does that mean you're not related to that person? No. Does that mean you are barred from making pierogies with the time-worn recipe? Of course not. They are still part of your family tree and are part of your heritage.

DNA is not the same as inheritance. DNA ancestry tests classify your DNA by the geographical regions from which you probably inherited it. But not everything about our family histories is geographic.

These tests do not tell us about the languages ​​our ancestors spoke about the food they ate or about whether they were celebrated or persecuted. They do not say much about how our ancestors lived or traveled. For example "Ashkenazi [a.k.a. Eastern European] The Jewish populations, which were very migratory, tended to marry within the group, "says Pickrell. 23andMe could combine you with an Ashkenazi heritage, but perhaps not with a specific geographic location.

Human history is a messy, migratory affair, too complicated to trace simply by using our DNA. And the exact percentages of where our DNA comes from may not matter either. If your brother inherits a little more Scandinavian DNA than you, does that make them more Scandinavian? Do not.

For these reasons, many are uncomfortable with the idea of ​​inheritance as something that needs to be corroborated with evidence of DNA – or that people belong to a particular ethnic group based on a trivial amount of ancestry. The ancestry of DNA opens a small door to our past. We can learn things like the fact that many tens of thousands of years ago, humans and Neanderthals mated, though we can only speculate (and in fascinating ways) why.

But it's just a little door, an imperfect guide.

"It's valuable information, but it will never be final," Pickrell says.

Further Reading: What the New Science of Genetics Really Tells Us About

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