Medical Genetics
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Medical Genetics


Now after you’ve had ancestry testing or any
sort of genome wide genetic testing, you can learn some interesting information about yourself. It turns out that not all of those individual
differences that are genetic mutations, SNPs, that distinguish human populations, are neutral. That is, they only tell us about our ancestry,
they don’t do anything to us personally. Some mutations, in other words actually cause
genetic disorders or diseases. And some of those genetic mutations that distinguish
people are also related to genetic diseases. So one common example is Tay-Sachs, which
is a common mutation in a gene that’s related specifically, normally, to the Ashkenazi Jewish
population. That’s a case where there’s a mutation that’s
both common only to one group of people, or almost only one group of people, and relates
specifically to a human disease. I want to tell you briefly about one medically
relevant mutation in humans that’s also used in ancestry testing, and that is the case
of lactose intolerance, the ability to digest milk products. In most humans, in the adults, we lose our
ability (the common thing is to lose the ability) to digest milk and milk products. It’s common for babies, because of course
we’re all meant to drink milk, and milk only, as infants, but then as we age, we’re normally
going to lose the ability to tolerate milk. But there are some parts of the world, in
the Western Sahara, in Scandinavia and the British Isles, and also in Saudi Arabia that
there are small groups of people that evolved the ability to keep digesting milk products
in adulthood, and so those three groups all have mutations in or near a gene (this is
a screenshot up here from the human genome browser: a website you can go to to look at
the human genome sequence) in one of these populations. There’s a mutation called… (I can’t read it from there)… it’s called
RS182549. It’s just a code that geneticists give to
one single nucleotide polymorphism, one SNP mutation, and it’s nearby, but not in, the
gene that encodes lactase. So here, on this part of this chromosome,
chromosome two in humans, is the gene called lactase (LCT). It’s a gene that encodes a protein (an enzyme)
that is the enzyme that breaks down milk sugars; that lets us digest milk products. So, that gene is normally turned on in infants
so they can digest lactose, and then in most humans it turns off later in life, and that
leads to lactose intolerance. It turns out this single nucleotide polymorphism
has two forms. You can either have a C at this specific spot
in your genome, and that’s the common or typical form that leads to lactose intolerance. If you have a T instead of a C at this one
spot, on this one chromosome, that’s associated with (associated with: not necessarily always
causes but normally causes) lactose tolerance. And that mutation is over here in a different
gene, the gene that’s next to lactase. There’s a second gene here on chromosome two
right next to it, and this mutation is inside this gene, but its effect is on whether or
not that lactase protein gets produced into adulthood. That’s really interesting. Scientists understand the basics of why that
is, and I won’t explain it to you now, but maybe in a future video. The T form exists mostly in Western Europe,
but when scientists looked at the genetics of people from Western Africa and in Saudi
Arabia, they didn’t necessarily see that T. This raises a really important point, which
is that different mutations, like the T at RS182549, can cause lactase to be expressed
(the protein produced into adulthood), but that mutation is not the only mutation in
all of our chromosomes that could lead to the same result, production of lactase in
adulthood. Presumably, these other two populations of
humans have different mutations somewhere else in their genomes that still let them
have the same trait: the trait of lactase production in adulthood. And so I want to give reference or give a
credit to these three…four groups that…these are their citations to the primary literature,
the publications. The first publication is the identification
of lactase, the C and the T types, as being related to lactase persistence: the ability
to digest into adulthood. The Ingram et al. article is the one that
showed that there was the T mutation associated with lactose tolerance, particularly in Northern
Europe, Scandinavia, and the British Isles. The third reference here, Gerbault et al.
is the one that showed the persistence of lactase in these three separate groups, but
not looking necessarily at the genetics. Tishkoff et al., this is the last reference
down here, did actually show that in one African population there actually was a totally different
mutation in that group that does cause lactase persistence in adulthood, proving that point
that I made a minute or two ago, that different mutations in different parts of the genome
can still make the same effect, the same trait, the production of lactase into adulthood. The reason that genetic testing isn’t great
at predicting disease is because of that fact: that different mutations can produce the same
trait. So, just because you get your genome sequenced,
or genetic testing, if you found out your genotype at RS182549 and it said you were
C, typical, that is you were probably lactose intolerant, that doesn’t mean you are lactose
intolerant, because there might be some other mutations somewhere else in the genome that
causes lactase expression in adulthood and allows you to be lactose tolerant. That’s another point about genetic testing. Just because you get genetically tested doesn’t
mean you’re going to get a particular disease, because most human diseases rely on the impact
and the effects of multiple genes, sometimes spread across multiple chromosomes. So, if you just look at one site on one chromosome,
you can say maybe this is 90% predictive, but there are very, very few human medical
diseases and disorders where a single gene causes the entire trait. The last point to make about genetic testing
and medical testing is that, not related to genetics, there’s a huge impact of environment
on your phenotype: on disease risk. Genetics is not everything. It’s both nature and nurture. It has something to do with your genotypes
and your DNA sequences, but then there’s a large component that has to do with what you
eat, what air you breathe, and so forth. Related to lactase persistence then, as a
test of how accurate some genetic testing companies are, a few years ago I had my DNA
tested by two different companies, just to compare which one was better than the other. I’m not going to tell you which companies
I used, but I just wanted to show you an example of the results that I got. The first thing that I saw when these companies
sent my testing back to me was the world map shaded in with colors and your probability
that, not surprisingly for me, I’m mostly Scandinavian with some British Isles ancestry
and maybe a little bit of an otherwise continental Europe: France, Germany, maybe a little Italian. Nobody was shocked by looking at me, and I
already knew that my ancestry was mostly British and Scandinavian. But what was even more interesting to me was
when I started digging into the data you can download from these companies after you get
your genetic testing. You can actually get from them, for free,
you can download it usually from your user account, a spreadsheet or a text file that
has all of the different SNPs that they looked at and will tell you what letters were in
your genome at each spot that they looked at. So it’s not just the already-interpreted-for-you
color-coded map, you can your genetic information. And so here, this is a screenshot from the
Excel file, this spreadsheet. At this row, the 91,000th something SNP that
they looked at was RS182549, the one that predicts, to a certain extent, lactose tolerance. I will never give up eating cheese. I am totally lactose tolerant, and I love
cheese and ice cream, so I knew that I was lactase persistent; lactose tolerant. And I have the TT type. What that means is on both of my chromosomes,
there’s a T at that spot. Remember from the previous segment that the
T is associated with lactase persistence, the ability to digest lactose into adulthood. And so at this chromosome, on chromosome two
at about, oh my goodness, 136 million base pairs from nucleotide one to 136 million base
pairs in, at that chromosome, this position, I have at T on both of my chromosomes. That’s what the genetic testing company did
for me. But not just at this one nucleotide, they
did it so many times. They actually looked at 720,351 different
SNPs in my genome. So they took all of my DNA, they threw out
all of the data (or they didn’t even collect the data) that are those parts of the chromosome
that are identical pretty much no matter which human you look at, what race, what ethnicity. They are only looking at these ones that differ
between races, between ethnic groups. It happens that this mutation is one that
most genetic companies look at, partly because of what I told you previously: this mutation
is associated with where you’re from in the world. This company looked at 720,000+ SNPs, If you
think about having 23 different chromosomes in humans, that means they’re looking at about
31,000 different spots on every one of our chromosomes. It’s not quite true because the chromosomes
are different sizes, but the distribution of single nucleotide polymorphisms, mutations,
across the chromosomes is pretty much equal. In other words, looking at 23 chromosomes,
these companies have genetically tested, or determined my identity, at about 0.02% of
the entire size of my genome, which is about 3 billion nucleotides. If you look at 720,000 or so, you’ve read
about…a tiny fraction of the genome. You can do this too at RS182549. Now, I know that I’m likely to be lactose
tolerant. If you want to download your genetic testing
information, your ancestry testing information, you can start, if you know which of these
mutations, which of the RS’s are associated with certain human diseases (which you can
find out on the internet) you can get medical information about yourself from your ancestry
testing. And that raises one of the most important
points about considering whether to get your ancestry testing done. Mainly you want to think about privacy concerns. How is the company storing your information? Who do they release it to? Will they ever give it to law enforcement
if law enforcement comes knocking with a warrant or something like that? Because what if an insurance company somehow
got ahold of your genetic testing information and they started looking at all of the different
SNPs that they know are related to different susceptibilities to human diseases? That’s been a concern for a long time about
genetic testing and it’s, in my opinion personally a bit overblown, but it is always possible
that that sort of scenario could happen someday. If somebody gets your genetic information,
they can find out certain things about you, and if that did happen to wind up in the hands
of some nefarious actor, it doesn’t have to be specifically an insurance company of course,
that could cause you problems later in life. So a few things to think about in terms of
genetic testing, and I hope you learned a lot and enjoyed this video. I’ll see you in the next one.

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