Ancestry Testing

Ancestry Testing


In this video, I want to explain to you how
genetic testing works, and specifically ancestry testing. I’ll go through, briefly, what genetics is,
in humans, and how genetic testing works, and then at the end, I want to close talking
about a few cautions that you might want to think about if you’re considering genetic
testing for yourself, or for your family or friends. To understand how genetic testing works, it’s
first necessary to understand humans, and their migration through the world, and why
different human populations are genetically different, and how that can be tested. To start, we start in Africa, where the ancestor
of all modern humans lived. There’s a population that was the ancestral
population, so think of this as the start of the human family tree. Everybody came from this part of the world,
and then they migrated. Some populations migrated south to Southern
Africa, where there are people like the San people, one population of humans that are
in Africa. From that ancestral population, there were
also migrations this direction to Australia, where we have, now, the aboriginal population. Also from that same ancestral group, there
was a migration across Siberia and the land bridge to Alaska, where now we have a bunch
of indigenous groups, like the Inuit. For today’s presentation, I’m just going to
be talking about these three groups as examples of how human migration has shaped the sequences
of our chromosomes, and how these three groups are genetically distinct. To move on then, we should think about what
the ancestor’s chromosome looked like, and how it changed to become the modern San, aboriginal,
and Inuit chromosomes. What I’m about to tell you is entirely made
up. They are example DNA sequences that I’ve created,
so they don’t actually reflect the real DNA sequences of these groups. For the ancestor, let’s talk about two different
chromosomes. We can talk about chromosome one, and we can
talk about chromosome two, let’s say, just two different chromosomes, for example. On chromosome one, the ancestor’s DNA sequence
might have been, in part of this chromosome, CTCTAGGAC, short example, and on chromosome
two, a different chromosome, a different piece of DNA, they could be CGCTCA. Okay, so thousands of generations ago, when
humans, all humans (Homo sapiens), lived in Africa, this might have been the sequence
of those parts of the chromosome. Then we can look at, as that chromosome in
part of Africa, as those populations grew, generation after generation, as they moved
across the world, shown here, every generation, random DNA sequence changes (mutations) occur. In the group moving south, that are not the
modern day San population, we might have, on the same chromosomes, in the same regions,
CTCTAGGAT, so it’s almost identical, but there’s one change, right there. There was a C in the ancestral population
in that part of the chromosome. Now there’s a T. And we can also look at chromosome
two and what might have happened to it, and we could say that that’s CGCTCT, let’s say,
so again, one change, one difference between generations ago and the modern population,
just one sequence change out of the six that we’re looking at currently. Let’s look at another couple of populations. We can see what the Inuit chromosome might
look like. It could have a difference there and a difference
there, so again, most of these positions, if you were a human, and if you were trying
to figure out where in the world you’re from, most of these nucleotides, the letters in
the DNA alphabet, don’t tell you anything about where in the world you’re from, but
a few do. So there’s a difference that distinguishes
Inuits from the ancestral population and the modern day San population. And we’ve got this position, that has changed
in both the San and the Inuit populations, from the ancestral condition. So a C became a T as those populations migrated
south, and that same C in the ancestral population changed to a different nucleotide (letter),
a G, as that population migrated across modern day Russia into Alaska. And again, on chromosome two, we can see similar
sorts of effects. So we have different nucleotides that have
individually changed compared to the ancestral population, and that’s the point here, is
that this is how genetic testing can distinguish ancestry. Some of these mutations tell human geneticists
where you’re from, because you inherited them from your ancestors that lived in one of those
particular populations. Then finally, we can look at the aboriginal
population, and look at one of their chromosomes, just again for example. Yet more distinct nucleotide changes that
will distinguish that population, in this case two nucleotides next to each other, from
the other populations. And on chromosome two, yet another set of
nucleotide changes. So you’ll notice, again, important points
are that some of these nucleotides are the same in all the populations, so they give
us no information about where you’re from. Geneticists then tend to ignore those letters
in your alphabet, in the genome, so we can ignore the C that tells us nothing about where
you’re from, if we were looking at this part of your chromosome, we can ignore the T, but
we might be interested in studying these sites on the chromosome where different populations
are genetically different. That’s one of the important background pieces
of information to have when you start thinking about how genetic testing works. With this information in hand, then it may
be easy to see how genetic testing works. First, we ignore the common, or shared, nucleotide
sites, the Cs, the Ts…, because who wants to sequence your DNA if it’s not telling you
something about who you’re related to? What we’re going to do, then, is the testing
companies where you send your cheek swab or saliva sample to, they only read the DNA at
certain parts of your chromosomes, the ones we already know can distinguish different
groups of people. So let’s say we’ve got your DNA sequence. We’re only going to look at, again, because
this is how the genetic testing works, I’m only going to show you the parts of your DNA
sequence that get returned from the testing company. When you get your testing back, they don’t
give you, directly, the individual letters at each position on every chromosome in your
entire genome, but you can get that information, and I’ll talk about that, perhaps on another
video. Let’s say you’ve got ATA there, and they look
at these last two sites on this chromosome, and you have an A and a T. Hopefully, you’re
already starting to try to figure out how this information tells you something about
which of these groups you might be related to. Then on this next chromosome, we’ve got multiple
sites that were informative, but you were an A at that second site, and a G at the fourth
site, and a T at this sixth letter. So we ignore all of the common letters, that
are common to all humans. That’s why we’re all humans. We’re all 99.9% genetically identical. And another important point about these nucleotide
changes. These are called single nucleotide polymorphisms. That means single letter changes, and we abbreviate
this SNP, S-N-P, single nucleotide polymorphism. These are the single letter changes that distinguish
individual humans. Important things to know about these are that
they’re random, that the change from one group to another is arbitrary. You become C to T, C to A, C to G. Any letter can change into any other letter
of the four letter DNA alphabet, and they’re randomly distributed across chromosomes. So although I’m showing pictures of just short
pieces, 10 nucleotides or six nucleotides of a chromosome…sorry, nine nucleotides,
six nucleotides. They’re not usually this close together, these
single nucleotide polymorphisms. This is just for ease of drawing on the lightboard,
so I’ve only got limited space, so I look at a limited number of nucleotides. Okay, so how does this tell us anything about
your ancestry? The analysis of your genetic testing comes
in when the geneticists at these companies that do the testing compare your letters to
the letters of all of the known human populations, not just these three. We don’t have ancestral DNA, so we can’t look
at the ancestral sequence, but these genetic testing companies have samples of people from
the San, the Inuit, the aboriginals, and so many other human ethnic groups and populations. So if we look at, for ATA, we see that the
Inuit has that same sequence, so you might say that that part of your chromosome looks
Inuit. This is one of the fallacies, or at least
a problem, with genetic testing, is that there are some of these spots, like this TA, is
shared. Because it’s ancestral, it was inherited by
the folks that moved south to become the San, and it’s also ancestral (also inherited) by
the Inuit. It only changed… That T only changed to a G in that aboriginal
population, so while a genetic testing company might say this ATA makes it look like you’re
probably part Inuit, they can’t rule out the possibility that that A came from an aboriginal
chromosome in your past, and that the TA came from somebody who was of San ancestry. So there’s never a clear answer to genetic
testing. It’s not fact, when you get your genetic testing
report back. It’s best guess. It’s probability and statistics, most often. So here, at the end of this segment of chromosome
one, we can look for an AT, and again, we see that the A is common to two different
populations, the San and the Inuit, but the T is found only in the San population, so
that might lead geneticists to suggest that you have part of this chromosome looks like
Inuit, part looks like it came from somebody of San ancestry. And likewise, over here with the AGT, it’s
hard to distinguish, then, for the A and the G, whether or not you might be Inuit or aboriginal. We’ll just say that that looks aboriginal,
just for the sake of argument. Then, that T also could be San or aboriginal. So at this point, there is some confusion
then, there’s never a clear conclusion, about what the ancestry of this person might be,
but there are some hints, and that’s one of the reasons that when you get an ancestry
test back, they don’t tell you specifically, “You are certainly 25% this population and
40% that population,” because there is some uncertainty as to how you assign these DNA
sequence differences based on what all of the human populations look like at the DNA
sequence level. One of the questions that hopefully you’re
wondering about is, “How do I have a chromosome,” like this example, chromosome one, “that’s
part Inuit, part San?” This is where it’s important to understand
a little bit both about how human reproduction works and also about how chromosomes evolve
over time, as a part of that reproductive process. The reason that we have chromosomes that can
look part one ethnic group and part the other, in terms of the nucleotide or letter composition
of the chromosomes, is that when sperm and eggs are being produced by humans, the chromosomes
are meant to, and actually break and switch parts with each other. This is a great use of… it’s evolutionary
biology. It’s a great use of molecular biology to generate
diversity in humans, because it scrambles (a little bit) the genetic code from one parent
to their offspring. This, for example, is why no two siblings,
even identical twins, are not exactly genetically similar, but especially non-twin siblings. They’re both from the same mom and dad, usually,
and yet they never look exactly the same. That’s because in your father, in his gametes,
in the sperm, the chromosomes that he inherited from his two grandparents are recombining. They’re breaking and swapping parts with each
other, generating new combinations of your genes and your genetics, so when a sperm and
an egg fertilize from two parents, that produces a genetically unique individual, one offspring,
and when the same process happens in the sperm and the egg that make the sibling, that sibling
inherits different combinations of Mom and Dad’s genes. This breaking process is what can break up
an entire chromosome over time. Generation after generation, more and more
of this, every generation, a chromosome rearranges itself (recombination) means that the bits
of ancestry, the whole chromosomes that were inherited from you by these ancestral populations
start to break apart, and those blocks of letters that tell you where your chromosomes
came from, Inuit, San, aboriginal, get smaller and smaller every generation. This is the information that genetic testing
companies can use to determine ancestry in terms of when they say, “You have a 75% chance
of being a third cousin of this other person who’s registered with our website,” this is
what they’re looking at, is if you’re a sibling, you probably only have one recombination break
point in each chromosome compared to a sibling. If you are a first cousin, then you might
have two break points on your chromosome, or more. All of this, again, is probability, that the
human geneticists at these companies work out, to try to guess (infer) how closely or
distantly related you are to somebody. It’s not just how similar the chromosomes
are, but it’s also the size and the structure of these groups of letters, that each show
different patterns of inheritance from ancestral populations. Now, there are a couple of flaws, major flaws,
with genetic testing. These are not necessarily common, but they’re
things you should keep in mind when you look at ancestry testing or genetic testing results. One of this is that the basis for knowing
whether or not your chromosome looks like somebody that is San, or Inuit, or Aboriginal,
or a Native American, or Norwegian, for example, depends entirely on whose DNA these companies
are using as the reference, the standard genome sequence, for people of each of these populations. Now, the geneticists that have worked on these
genomes of these people are pretty confident that they have what you might call, colloquially,
a pure aboriginal DNA sequence, or pure Inuit. But there’s always some probability that people
have mixed ancestry, but still claim that they’re in one of these groups. So there has to be a little bit of caution
given to comparing and interpreting your DNA versus people of other groups. There’s no perfect certain individual from
any of these groups that’s truly representative of the entire group. The other thing to keep in mind about genetic
testing is that mutations happen all the time. They happen at random places, on random chromosomes,
changing random nucleotides into other ones, Cs to Gs, Cs to As, and so forth. So for example, here in the San population,
we have a T, and you also have a T there. But that doesn’t necessarily mean that that
T derived, you inherited it, from somebody of San ancestry. It could be, however unlikely, that your actual
DNA sequence was… Again, just looking at the SNPs, ignoring
the common nucleotides, ATAAA, for example. So let’s say your parents had that sequence,
but when you were born, when the chromosomes that made you were being generated, there
was a mutation of what your parents’ A was to a T. Now all of a sudden, you might look
like San, AT, or you might have Inuit ancestry, AG, somewhere in your past. These random mutations that can happen… Again, they’re very rare. The probability of you having a single mutation
in one of the random spots that the genetic testing companies use to look for your ancestry
is really, exceedingly rare, but there’s a very slight chance that that could happen. So again, another thing to consider when you
interpret genetic testing results: that random mutations occur. That’s how we got diversity among people in
the first place, and it could happen individually in you, and that could slightly skew your
genetic testing and ancestry testing results.

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