Are they related to me? I still don't know…When last I left you, I was searching for my great-great grandmother’s DNA in my own DNA.  Remember, legend has it she was Cherokee and I wanted to confirm the legend with a genetic test from a company called 23andMe.

In my last blog post, I showed how the two most powerful ancestry tests, mitochondrial DNA (mtDNA) and Y chromosome, were useless to me in my hunt. Now I want look at the rest of my DNA.  So here we go!

The Y chromosome and mtDNA are a small fraction of my DNA—something like 0.8% of the total DNA in one of my cells.  But they are incredibly useful because they change very little from generation to generation.  The mtDNA I got from my mom is probably exactly like hers.  Same with most of the Y I got from my dad.

The other 99.2% of my DNA is a lot trickier to look at from an ancestry perspective because it has changed a lot from generation to generation over time.  For example, the chromosomes I inherited from my parents are not the same as the ones they have.  I got a mix of their chromosomes

For example, my mom had two copies of chromosome 1 (and two copies of her other 22 chromosomes too).   As you know, she passed one chromosome 1 to me (my dad gave me my other one).  But, through a process called recombination, her two copies of chromosome 1 swapped DNA so that I got a hybrid of her two copies.  I inherited a unique chromosome never before seen.

This is all well and good from a survival of the species point of view, but it is a problem for ancestry testing.  Imagine that instead of my mom, we look at my Cherokee great-great grandmother.  She has just had a child who inherited a mix of her chromosome 1’s.  This chromosome will look Native American and the child would appear half Native American.

Actually, the test isn’t perfect yet and so there isn’t yet a “Native American” set per se.  Instead, here is how 23andMe describes Native American DNA in their tests:

“…people who identify themselves as Native American exhibit fairly consistent Ancestry Painting proportions of about 75% Asian and 25% European, plus or minus 10%.”

This means the chromosomes the child got from his or her mom won’t look Native American but instead will look 75% Asian and 25% European.  (See a realted post of mine elsewhere for why it looks like this.) Now imagine that this half Native American child grows up and has my grandfather as his or her son.

My grandpa will inherit a mix of his parents’ DNA too.  In this case the Native American DNA will mix with the European DNA to create a hybrid.  On average, you would now see something along the lines of 37.5% Asian (this is a simplification but it gets us into the ballpark of the number we might expect).

Each generation would see, on average, a continued dilution of this Asian part.  My dad would have 18% Asian, I would have 9%, etc.  Here are my ancestry results (click the image to enlarge):

Not a hint of Asian.  Looks like my great-great grandma wasn't Cherokee.  Or was she?

There are lots of ways she could still be Cherokee.  First off, I don’t know how solid the 75% number is for all Native Americans.  I don’t know how many Native Americans are in their database.  I also don’t know how much variation there will be tribe to tribe.

Secondly, you may have noticed that I was very careful to always say, “on average.”  This is because the recombinations don’t have to be a 50-50 swap.  It is true that if you look at a large number of recombination events, the average will be 50%.  But individual recombination events can be biased towards one or more chromosomes.  Occasionally you’ll get mostly one chromosome and sometimes mostly the other.

Sort of like flipping a coin—do it enough and you’ll get pretty close to half heads and half tails.  But if you flip a coin twice, you might get one head and one tail.  And you might not.  Half the time you’ll get two heads or two tails.

This is less a problem than you might think with our chromosomes since the recombination is spread over 23 pairs with each pair being independent of the others.  But it can still throw a monkey wrench into the works.  23andMe actually has a nice chart that hints at this by giving the most likely range of possibilities.  Unfortunately, this chart didn’t come up with my results and I had to stumble on it while I was playing around.

Using the chart, I can see that the bottom end of my expected results in 0.24% “Native American” (if I am reading the chart correctly).  That is pretty low and it seems like a pretty minor mistaken assumption at the beginning might knock this down to zero.

So where am I after this?  Still in the dark.  This is actually how many genetic tests end up.

The positive result tells you a lot.  Had there been Native American DNA, that would have been a slam dunk.  (This isn’t always the case with genetic tests but it would be here.)  But there wasn’t.  Which means, given that I was on the edge of detection, that she may or may not have been Cherokee.

Now, this isn’t 23andMe’s fault.  The test itself couldn’t be conclusive given how far back we need to go and the DNA tests that 23andMe offers.  In fact, 23andMe does an excellent job of presenting the data.  There are pretty chromosome paintings, graphs superimposed on world maps, etc.  All very nice.

I am still worried that the explanations that go along with these images assume an awful lot of knowledge that most people might not have.  Without that knowledge, it can be hard to assess the significance of a certain result.  Next blog that’ll become even more important as I tackle health conditions.

Genetic tests often don’t give as much information as you might think.In a previous blog I talked about getting my DNA tested with 23andMe.  Well, I got the email the other day saying that my results were ready.  So I logged on and up popped this screen pictured to the left.

All sorts of goodies to try out!  I feel like a kid at Christmas.

The first thing I thought I’d do is check out my ancestry.  My grandfather’s grandmother was supposedly Native American and so I wanted to find out if I could see that in my DNA.  (This relates to my supposed relationship with the outlaw Sam Starr but that is a different story.)

23andMe has this Native American testing app in their 23andMe Labs section.  I clicked on my data and up popped this result:

Recent Native American ancestry is unlikely

Has it all been lies?  My great, great grandma wasn’t Native American?  Not so fast…

A “no” answer on a genetics test doesn’t necessarily tell you a lot.  (And sometimes, the “yes” answer isn’t so helpful either!)   Now as a geneticist, I know the drawbacks of ancestry tests like these.  What I wanted to see was if 23andMe did a good job of explaining them.

I first checked out my mitochondrial DNA (mtDNA) and my Y chromosome data.  These DNA don’t change a lot from generation to generation and so are really good at tracing ancestry many generations back.  Their downside for me is how they are passed down.

The Y chromosome passes from father to sons.  My great, great grandma didn’t have a Y to pass on so of course my Y chromosome data wouldn’t show that she was Native American.

mtDNA passes from mom to her children.  At first this sounds promising since we are talking about my great, great grandma until we realize that I am related to this woman through my grandfather.  His mtDNA died with him (except for his female relatives and their descendants) so that is lost to me as well.

Here is what 23andMe has written under interpretation of my mtDNA and Y chromosome results:

This mitochondrial DNA haplogroup is inconsistent with Native American ancestry along the maternal (mother's mother's mother's …) line.

This Y chromosome haplogroup is inconsistent with Native American ancestry along the paternal (father's father's father's …) line.

I suppose this says what I just said but I am not sure how many people would really appreciate the limitations of mtDNA and Y chromosome data from this explanation.  There wasn’t a link to a more explicit discussion of the limitations of this sort of testing and there wasn’t anything I could see from a quick glance at the ancestry part of the site either.  An explicit explanation would be good or maybe a figure like this one:

To me, this drives home the point that there is a whole lot of missing ancestry.  It might help if they had some sort of family tree app where you could indicate as much as you know about family relationships.  Once you’ve inputted the data, it would spit out what tests results would be useful to look at.

So the mtDNA and Y chromosome test results are of little use to me in this quest.  (And of little use to me in general as it confirms my pasty whiteness.)  Next blog I’ll deal with the rest of my DNA and what that can and can’t tell me about my great, great grandma.

Do you have a note from your doctor?

So much information, so little understandingOn June 9, the California Department of Public Health (CDPH) sent letters to 13 different direct-to-consumer genetic testing companies telling them that they were not in compliance with California laws and needed to stop providing testing. The two main issues appear to be:

1. The testing facilities were not licensed correctly.
2. The tests were ordered without the request or counsel of a doctor.

This seems to me to be the opening salvo in an upcoming war between the government and these companies about DNA testing. The government wants to protect the consumer from getting incorrect results and/or misinterpreting the results they get. The companies want to provide people with information about their own DNA. I have to say I am unsure where I stand on this one.

On the one hand, there are some companies out there selling snake oil. For example, anyone claiming that they can provide a set of nutritional products based on your genetic test results almost certainly should be shut down.

And I would guess that the CDPH is not going after purely recreational companies like those involved in ancestry. I can't imagine why a doctor would order that kind of test. If these letters target ancestry companies, then whatever laws are involved should be changed.

There are also companies that comply with the current California laws. One of the most prominent is DNA Direct. This company follows all of the rules of the state, only offers well validated tests that are performed in a CLIA lab, and provides genetic counseling so people can understand the results they get.

But what about the companies between DNA Direct and ancestry testing services? Although we don't know for sure, the CDPH seems to have targeted many newer companies that look at hundreds of thousands or even millions of DNA differences at once throughout a person's DNA.

The three main companies that I know about that are in this gray region are Navigenics, 23andMe, and deCODEme. Navigenics is a different sort of beast from the other two in that it only provides information on DNA differences that have a well established link to a disease and they also provide genetic counseling. The other two can really be thought more of as recreational genomics at this point.

23andMe and deCODEme give a client all of their information and then tell the client what is known about each DNA difference. They offer ancestry, trait, and disease information bundled up in a single 1000 dollar test.

These companies count on the consumer being able to digest all of that data and recognize what is a strong and/or important correlation and what is not. This is the point where a group that includes the government, doctors, and many academics differ with these companies.

Once we make sure that the testing is done well, the question really boils down to whether or not the consumer can handle all of the information*. Can consumers interpret these kinds of results and know when to seek help and when not to?

The answer is that some can and some can't. So how do we protect those who can't but still allow people access to their own DNA? Or should we protect consumers at all from their own DNA information?

*There is also the stipulation about a doctor ordering the test but frankly I don't get that one and am not sure it should be part of any consumer protection.

Copy of the letter from Wired Science