"Mysteries of DNA" image courtesy Mark H. Adams. Full-size version.

As anyone who follows this blog knows, I recently took a 23andMe genetic test and have been blogging about it ever since. Today I thought I would focus on one of the fun parts of the service: traits.

Lots of our traits are at least partly dependent on our genes. So a genetic test should be able to tell me a bit about what I’ll look and even be like in the future. It may even tell me what I can expect for my kids.

Here is what is available on the 23andMe test (click on the image for a larger version):

As you can see, some of this is pretty obvious…I know my eye color for example. It is kind of cool to see my blue eyes written in my DNA but not necessarily that helpful. When I click on eye color, I find out that people with this particular bit of DNA have a 72% chance for blue eyes, a 27% chance for green and a 1% for brown. (Incidentally, this 1% brown is probably a big reason why blue-eyed parents can have a brown-eyed child.)

What would have made this report more interesting for me is what it meant for my kids’ eye color. Does it mean I’ll have blue-eyed kids? This of course depends on my wife’s genes but it would be cool to have the option of including my wife’s data to find out.

Other less obvious traits were very interesting to me. The results say that like most mammals, I should be lactose intolerant. Which I am not—I’m fine drinking milk. So did 23andMe get it wrong?

Probably not. The science is pretty good on this topic. People with a certain difference in their lactase gene almost always lose the ability to make lactase as adults. No lactase means lactose intolerance.

When I dug deeper on the website I got some hand waving about other genetic influences or the environment. A better explanation is that I will probably become lactose intolerant at some point in my adult life—it just hasn’t happened yet.

Losing the ability to make lactase is a gradual thing. It happens to some people early in adulthood and others later on. I am probably one of the “later ons.” Something to look forward to…

One trait that I’ve always been a bit interested in is HIV resistance. Some people are more resistant to infection by HIV (the virus that causes AIDS). If these people do become infected, they tend to develop AIDS symptoms much more slowly as well.

In Europeans at least, this resistance has been tied to a DNA difference called CCR5-delta32. The people who are resistant to infection and who develop AIDS more gradually tend to have two copies of this DNA difference.

This DNA difference has been proposed to have become common in Europeans because it also makes people resistant to either the plague or smallpox. If true, my ancestors must have died like flies from the plague or smallpox because I don’t have the DNA difference.

I also now know about what my DNA tells me about my earwax, how I respond to a certain bitter chemical, and whether I flush from alcohol. These are sort of interesting but not very.

This part of the 23andMe experience is kind of fun though. I really enjoy it when genetic theory matches up with what I can see about me. It sort of validates genetics…

What can genetic testing tell you?

A while back I took a 23andMe genetic test that looks at over 600,000 different spots on my DNA. The last few blogs I have been going over my genetic test results with an eye on how useful they are. And how well the results are explained.

Last blog I wrote about how current genetic tests aren’t that great at predicting your risk for common, complicated diseases like diabetes or Alzheimer’s. This time I thought I’d focus on what today’s genetic tests can be very good at and whether or not 23andMe does a good job with these.

Current genetic tests are very good at predicting your risk for rare, simple genetic diseases like cystic fibrosis (CF) or Huntington’s disease (HD). And at predicting the chances that your kids will get these diseases too.

Genetic tests for these diseases work because most of them are caused by a single gene gone awry. Testing for a single gene is relatively easy.

For example, most cases of CF happen because of known differences in the CFTR gene. A genetic test can look for these differences and tell you if you and/or your spouse have any of them. If you both do, they can also give you a pretty good idea about the chances that your kids will get them too.

Of course, we don’t know all of the differences in the CFTR gene that can cause CF. And some differences only cause CF some of the time. And there are people with everyday, run-of-the-mill CFTR genes who get CF because of differences in different genes.

Still, as genetic tests go, these are pretty good. If a test comes up with a known CFTR difference that causes CF, then you have a pretty good idea of what your chances for developing CF are. If your spouse gets tested too, then your kids’ chances can be determined as well.

So how does 23andMe do? OK, I guess…

First off, they look at eight of these sorts of diseases under a category called Carrier Status. The diseases they look at are shown in this image:

For me, the first big result is that I am a carrier for a variant that can lead to hemochromatosis. This isn’t surprising since 1 in 8-12 people of Northern European descent in the U.S. are too, but it is definitely something to watch out for. It may be important for my wife to be checked too so we can make sure none of our kids got two copies. (Luckily hemochromatosis is easily treated by giving blood on a regular basis.)

Some of the other results are less illuminating. For example, I do not carry the CF difference they test for (delta F508). This is of course great news. Unfortunately, this variant only accounts for about half of the CF cases out there. Which means I could be a carrier for CF, just not a carrier of the most common variant that they happen to test for.

The same thing goes for most if not all of the other carrier status diseases (sickle cell anemia is an exception). Some like BRCA (breast cancer) are as poorly covered as CF while others like Bloom’s disease cover a larger percentage of cases.

23andMe is pretty upfront about the limitations of their testing once you dig a bit into the results. But still, if they’re going to look at 600,000 different parts of my DNA, you’d think they could add a few more to give me a stronger answer about whether or not I am a CF carrier.

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.

You've probably heard about some of the breakthroughs in personal genome sequencing, where companies take a look at your DNA and send back your risk profile. That can be confusing information to have (check out this post from Quest blogger Dr. Barry Starr for his take on it). But there's a flip side to all this genetic research that doesn't have to do with risk: personalized medicine. That's where doctors can customize medical treatments to fit your genetic profile.

Right now, there are only a handful of drugs that are labeled with genetic information, so doctors can take it into consideration. (Here's an article from the New York Times that gives an overview).  But that doesn't mean existing medications are left out.  I spent some time with Deanna Kroetz in this story, who studies pharmacogenomics at UC San Francisco.  She explained that differences in our DNA can cause some of us to process drugs at different rates. We all metabolize drugs with enzymes in the liver, but based on expression of our DNA, we may have different levels of enzymes or our enzymes may not function as well.

There are plenty of other things that affect how we process drugs, like our diet or other drugs we're taking. But these genetic differences mean some people metabolize drugs quickly and others metabolize them slowly. One example that many people are familiar with is codeine.  Codeine is converted into morphine by our bodies and it's the morphine that actually has an effect — but that conversion depends on a particular enzyme. Some people have very low levels of the enzyme that's needed, so codeine doesn't do much for them.

They're also studying another drug response mechanism at UCSF and it has to do with our cells. Many drugs have to go inside our cells in order to have an effect, but if you think back to high school biology, you might remember that cells are protected by membranes.  It takes transporters – those special gatekeepers sitting on the cell membranes — to allow things in.  They also can spit things out of cells.

I spent some time in the lab with Rachel LaFond, a graduate student at UCSF.  She was running experiments on one particular transporter known as ABCG2. This transporter is particularly good at spitting things out of cells. Normally its job is to kick toxins out, but some cancers have been able to hijack this machinery.  Cancer cells with an over expression of this transporter can spit out chemotherapy drugs, which means they aren't helping the patient.  LaFond is working to understand this variation better, so they could one day develop a genetic test for it.

Listen to the Personalized Medicine radio report online.

Hopefully this DNA analysis data will be better at telling my future than tea leaves or goat entrails.Well, I have finally decided to do it.  I have ponied up the money and signed up for 23andMe's DNA test.

This is a test that will look at over 500,000 different spots on my DNA.  From the results I'll be able to learn about my future health and my past ancestry.  Well, as much as I can learn given the current state of genetic knowledge.

And there's the rub.  I have held off on doing this for quite awhile because I am just not sure how useful it will be.

Most of the DNA studies on the big diseases like schizophrenia, autism, diabetes, heart disease, etc. have not been that conclusive.  They tend to find bits of DNA that have a very small effect on risk.

Undoubtedly as more studies are done, we'll find lots of bits of DNA like this and we'll be able to figure out our risk more accurately by adding them all up.  But we're not there yet.  In fact we're probably years away from being able to do this.

I have also been a bit squeamish about sending my DNA to a company.  Yes, I know they'll be careful but still…it's my DNA.  You can't get any more personal than that!  I would hate for someone to get that information and use it against me (think insurance agent).

So why did I finally decide to go through with it?  One reason is that I get a lot of questions from people at the Ask a Geneticist site about how useful or good the test is.  Right now I have to tell them I don't know.  I'd like to be more helpful than that.

I also think that it will be fascinating to see all of my bits of DNA.  This is the stuff that is a big part of making me who I am.  It will be so cool to look into that crystal ball even if the future I see is a bit murky.

Of course as a big old science geek I'll be interested in that stuff…it's my bread and butter!  What I also want to do is try to imagine what the test is like for someone who doesn't go all gaga for genetics.  How is it for people who aren't necessarily mesmerized by the beauty of DNA and instead are mostly interested in diseases, traits, and ancestry?

I guess I'll find out soon.  I sent my spit in last week.  I'll keep you updated in future posts.

In a truly awful decision reminiscent of Gore vs. Bush, the Supreme Court has decided that there should be no federal mandate for genetic testing after someone has been convicted. Even though DNA evidence can free innocent people who were wrongfully accused. How absurd is this?

It is especially hard to understand when there is ample evidence that there are plenty of innocents in prison. And when a DNA test can prove so conclusive in showing their innocence.

A case I use in a high school activity (and which will be highlighted in the new Technology Benefiting Humanity exhibition at The Tech) involves Marvin Anderson. He is an African American who was convicted of rape by an all white jury in the South.

Court TV produced a great documentary that details all of the mistakes that sent Marvin to prison. And how the Virginia state government, much like our current Supreme Court, fought the simple DNA test that eventually proved his innocence.

Marvin was a suspect because he had a white girlfriend and the rapist had said that he had a white girlfriend during the attack. In a photo line up, Marvin’s was the only picture in color. Then, in the real line up, Marvin was the only man who had been shown in the photo line up.

Marvin’s lawyer represented the man who had really committed the crime. The trial lasted one day and as I said, Marvin was sent to jail by an all white jury. And while Marvin languished in prison, the real rapist confessed but the judge threw out the confession.

This is when the Innocence Project took up the case. The Innocence Project uses genetic testing to free innocent men and women. After hearing the details of Marvin’s case, they decided to help him clear his name. And it was not easy!

First off, they had to find the evidence from the case. This is often hard to do because evidence gets thrown away after a certain amount of time.

But, by a miraculous fluke, the Virginia government found the evidence from the rape kit… it had been saved in a lab notebook. So all that needed to be done was to see if the DNA from the crime scene matched Marvin's. If it didn’t, then Marvin most likely was innocent.

But the Virginia government would not allow the evidence to be tested. Apparently, just like the Supreme Court, procedure mattered more than innocence to the bureaucrats involved.

How many people like Marvin Anderson are waiting for the justice system to do the right thing?
Finally, in 2001, after Marvin had been in jail for 15 years and spent four years on parole, Virginia passed an Innocence Project backed statute that allowed DNA evidence to be tested in some cases. Marvin’s was the first evidence tested under the new statute. He was found to be innocent and the police were able to use the evidence to catch the real rapist.

If the Virginia government had not done the right thing, the real rapist would be free to continue committing crimes. And everyone would still see Marvin as a rapist.

There are undoubtedly Marvins rotting in jail in the three states that don’t allow for genetic testing after a conviction (Alaska, Oklahoma, and Massachusetts). And other Marvins are probably in those other states that only allow genetic testing in certain situations.

The Supreme Court could have given all of these innocent people the chance that Marvin finally got after 19 years. But five justices decided against doing that.

Now I suppose there is probably some legalese reason why the Supreme Court ruled that innocent people should stay locked up. But I am not lawyer enough to understand it. And neither are the Marvins still out there, waiting for justice.

It will probably take more than a human FOXP2 gene to reach this future.Scientists have started to look at DNA to try to figure out why we can speak and other animals can't.  One gene that has caught their attention is called FOXP2.

People with a certain version of this gene have trouble forming words and speaking but are otherwise OK.  This is exactly what you would expect if a gene were primarily involved in speech.

One way to test this idea would be to put the human version of the gene into an animal and see what happens to that animal's speech.  A natural candidate would be the chimpanzee.  Humans and chimps are around 98.8% similar at the DNA level* and their FOXP2 gene has only two differences.

Unfortunately (or fortunately…), we can't yet do this experiment because we aren't very good at changing a chimp's genes.  But what we are good at is changing a mouse's gene.  And this is exactly what scientists did in a new study.

The scientists changed a mouse's FOXP2 gene into a human's.  Now no one expected that we'd have a Mickey Mouse on our hands.  Mice just don't have all the equipment for speech and it is really unlikely that the only difference between mice and people in terms of speech is this gene.

But by putting a human FOXP2 gene in mice, we can learn some things about how the gene influences human speech.  Does it change the vocalization part of the brain?  Does it change something with mouth anatomy?  Something with breathing?

The results with these mice were interesting.  They weren't suddenly chatty but changing the gene definitely caused the mice to emit different squeaks than their natural cousins.  The vocalization part of the mouse's brain also changed.

These results suggest that FOXP2 affects human speech at least partly through changes in the brain.  And that if you give a mouse a human Foxp2 gene, you change the way it communicates.

The next steps are a little harder to figure out.  We do know that Neanderthals had the same FOXP2 gene that we do.  Perhaps by comparing human, chimp and Neanderthal DNA we'll be able to find other genes involved in speech too.  We'll have to wait a few months for this kind of analysis as the Neanderthal genome isn't quite done yet.

*When we include extra copies of some DNA and missing DNA, the similarity goes down to 96%.

Here is a video discussing the results of the study.

The swine flu virus. Credit: C. S. Goldsmith and A. Balish, CDC.

As this story is being produced, the reports on swine flu are changing hourly. Cases are popping up closer and closer to home, and the CDC is updating several times a day on the spread of the virus, and plans to fight it.

The $64,000 question is how worried we should be.

Swine flu is largely untreatable: The two effective antiviral drugs, Tamiflu and Relenza, must be taken within 48 hours of infection to stop the spread of the virus.

That leaves a vaccine. Vaccines are relatively straightforward to create, but they take time. If swine flu becomes a deadly pandemic (meaning it's not only widespread — a pandemic – but more lethal than it appears to be so far) the demand for vaccines would likely far outpace supply. According to Art Reingold, at UC Berkeley's School of Public Health, it could take years for doses to reach everyone in the world who's vulnerable to the disease. Here in the US, we have very few vaccine producing facilities, which means we'd be competing with other countries' priorities to treat their own citizens.

Our story focuses on what could, one day, be the answer to pandemics like this one: a universal vaccine. Scientists like Harvard Medical School's Wayne Marasco believe that, in just a few years, we might be able to inoculate ourselves against nearly all influenza viruses – like a tetanus shot, against the flu. Universal vaccines will come too late for our current swine flu pandemic. But they may well be our response to pandemics of the future.

Listen to the Swine Flu and You radio report online.

Shows like CSI can increase the public's awareness of geneticsOne of the most fun parts about my job is answering people's genetics questions at our Understanding Genetics website.  We get around 200 questions each month from all over the world and they definitely keep me on my toes.

They also give me a feel for what is going on with science in popular culture.  I can tell this by looking at Google Analytics data and seeing which of our previous answers has had an upsurge in visits.  (We post around one new answer online per week.)

For example, whenever PBS airs a show on how a mutation called CCR5-delta 32 may have made people resistant to the plague, I get an uptick in the hits on the answer that deals with that topic.  When House (a show on Fox) had a character say that of course someone was adopted because he had a cleft chin and his parents didn't, I got an uptick on the Chimeras start out as fraternal twins that fuse together at a very early stage.  What this means is that chimeras have two sets of DNA.  Some of their cells have the DNA from one twin and the rest of their cells have DNA from the other twin.

As you can imagine, these folks can wreak havoc with a police investigation!  What happened in the CSI episode was that the DNA from the crime scene did not match the DNA from the most likely suspect.  In the end we find out that the suspect is a chimera and that the evidence left behind at the crime scene had one set of DNA and that the blood they tested had a different set of DNA.  From the same person!

It is great that there is so much science starting to seep into popular culture.  If the science is accurate, it is a great way to get people involved in science.  I just wish it was accurate more often.