Missing two chromosomes but doing fine. A partial karyotype of a man with 44 chromosomes.

A doctor from China contacted me through this blog with some exciting news. He had found a patient with 44 chromosomes instead of the usual 46. And the patient was perfectly normal as far as anyone could tell.

The doctor contacted me because the story of how this patient ended up with 44 chromosomes mirrored my story of how humans may have gone from 48 to 46 chromosomes a million or so years ago. The idea that human chromosome reduction could happen this way was theoretical when I wrote about it. Now we have living proof that it can and does happen.

Sticking Two Chromosomes Together

At first it might seem weird that losing a couple of chromosomes had no real effect on the patient since losing even one is usually fatal. But his case is different because he didn’t really lose two chromosomes (and all of their essential genes). Instead the chromosomes ended up stuck to two other chromosomes. So he has the same genes…they are just packaged differently.

When this happens with a single chromosome, it is called a balanced translocation. These are more common that you might think with about 1 in 1000 people having one.

The way to end up with 44 chromosomes like our patient requires that both parents have the same balanced translocation. The only way this is at all probable is if the parents are closely related. In this case, they are cousins.

I won’t go into the details (click here to learn more) but these parents had a 1 in 36 chance of having a child with a double balanced translocation. And this is our patient.

From 48 to 46 to 44?

As I said before, a big reason why this is all so interesting is because it provides confirmation of one way that humans may have gone from 48 to 46 chromosomes so many years ago. The first step might have been similar to what happened to our patient. Two closely related parents with the same translocation have a child together that has fewer chromosomes.

Back then, chromosomes 12 and 13 fused together to create what we now call human chromosome 2. The fused chromosome then slowly spread through the community. And then, for some reason, the group of humans with 46 chromosomes eventually supplanted the group with 48.

We can’t know for sure, but this may have happened through some random event where the 48 chromosome humans were mostly wiped out and the humans with 46 chromosomes were spared.  Humanity has nearly been wiped our before with the most recent case being a volcanic eruption 75,000 years ago.

If something similar happens in the future, I wonder if people will be questioning our close relationship to chimpanzees. “How could chimpanzees be our closest relatives,” these future folks might ask, “when we have four fewer chromosomes than they do?”  This assumes, of course, that the number of chromosomes has not changed in chimpanzees by then…

Current DNA tests could not have predicted that George W. Bush would be our 43rd President of the United States.

Time recently had a great article on helicopter parents. These are the parents who hover around their kids, protecting them from any harm. They are undoubtedly doing this to ensure their kids’ success in life.

I don’t want to get into the plusses and minuses of this parenting style…to each his own. What I do want to do is to warn them away from a new genetic testing company that seems designed to target them.

This testing company, called My Gene Profile, claims to be able to use genetics to help parents figure out where their child’s inborn talents lie. The idea, then, is for parents to point their children towards interests or careers that match up with what the genetic test says.

The talents the company is looking at are not simple ones like tongue rolling or bending your thumb back (neither of which we can yet determine genetically). They claim to be able to tell you if your child will be smart, creative, good at sports, and near as I can tell, five other similarly broad traits.

This is impossible given our current knowledge of genetics. And frankly, I am not sure we’ll ever be able to figure any of this out with a simple genetic test. Most of these traits are more than just the DNA we inherit.

Let’s take IQ as an example. Most of the studies I have seen point to about half of someone’s IQ coming from genes and the other half from the environment. Any test done right now won’t look at how the environment affected a child’s DNA. And they certainly won’t look at how the environment influenced the growth and development of the brain or how it affected synapse connections or about a million other things to do with intelligence and the brain.

Still, 50% from genes is a lot. If we could get a complete readout of how our genes influence our IQ that might be at the very least interesting. But we can’t.

Scientists believe there are at least 100 genes that contribute to IQ. So far they’ve only identified a handful and none of them have been shown to have reproducibly significant effects on IQ.

For example, scientists have found that having certain versions of the CHRM2 gene affects your ability to organize things in a logical way. The effects aren’t huge though. 23andMe (a company that I have tested with) reports that the variations that they look at in this gene can lead to a 6 point swing in IQ. Woopty doo.

If you drill down a bit farther, some scientists claim that you can get much larger differences. For example, at the furthest extremes, people with one set of variations in this gene averaged an IQ of 85 while people with a second set averaged an IQ of 103. Sounds impressive.

Except that a larger follow up study was not able to see the same effect. In this study, scientists weren’t able to find any connection between variations in the CHRM2 gene and IQ. And CHRM2 is by far the best characterized IQ gene.

Most likely the way that genetics contributes to IQ is that each of the 100 or so genes tweaks IQ a bit higher or lower. So to get a complete readout on IQ you’d need to look at all of these genes. This is difficult to do right now since we only know about a few of them.

And to make things even more complicated, the genetic contribution to IQ probably isn’t a simple summing up of these different variations. They don’t exist in a vacuum—these gene variations all interact with each other too.

What this means is that we may never be able to get an accurate prediction about genetic IQ from our genes. There are lots of possible combinations all with different outcomes. In other words, everyone’s IQ genetics may be unique which would make predictions impossible.

The bottom line is that there is not nearly enough data out there to figure out someone’s IQ or intellectual potential. And this goes for athletic ability, creativity and any other similarly complicated trait. We can’t even predict eye color yet very well from our DNA!

So consumers be aware of what a genetic test can and can’t deliver based on what scientists know. Testing for cystic fibrosis, pretty good. Testing for intelligence, not so much.

A final example. Imagine that Einstein’s parents had tested his genes for IQ with a company that looked at four or five IQ genes. And let’s say that he happened to have versions of these genes that lead to a lower IQ. Of course, since it is Einstein his other 95 or 96 or so IQ genes swamp out the effects of these few genes. But the testing company misses this and recommends that he not take an academic career. A little knowledge is a dangerous thing.

*This is common with genetic studies. There is a promising result with a small group that disappears when scientists look at a larger group.

"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…

David experimenting with EEGLoyal KQED blog followers have been reading of Dr. Barry Starr’s experience getting his genes tested by 23andMe. He has tested his native American ancestry and evaluated his risk for diabetes. What if Barry took even more tests, from blood toxins to more genetic tests – would that result in a clearer picture of his health? That’s exactly the premise behind David Ewing Duncan’s new book: “The Experimental Man”.

David takes “guinea pig” journalism to super size me heights. He was tested by numerous genetic sequencing companies, had dozens of brain scans, gave gallons of blood for toxicity tests, even had a virtual colonoscopy to understand what “personalized” medicine means for him. His experimentation was divided into 4 categories: genetics, environment, brain, and body.

My favorite experiment was a memory test in which David and I both participated. The study was on how normal aging changes the neural mechanisms of memory and attention; a study run by Dr. Adam Gazzaley of UCSF. His lab uses a combination of techniques including fMRI (functional magnetic resonance imaging -measures blood flow using a big magnet), EEG (electroencephalography – measures electrical signals in the brain), and TMS (transcranial magnetic stimulation – using a magnet to “scramble” regions of the brain).

In this experiment, I was getting an EEG, designed to measure electrical signals of the brain, in this case studying regions controlling memory and attention. I was fitted with a stylish red cap, my head was covered with a conductive gel, and I was seated a few feet from a computer screen. After some careful measurements of my head, I was ready to go.

I was shown either a face or nature scene for a split second, then the screen went blank, then I was shown another face or nature scene. My task was to decide whether the two pictures were the same. Sounds exceedingly simple, but it was far from it. I left absolutely exhausted after just a few hours!

However, my results were excellent. I averaged about 95% correct over 3 hours. According to the researchers, that’s slightly better than the average 18-35 year old. David’s results were about the same, but he is more enthusiastic considering he’s closer to 50. Take a simpler version of a brain age test online.

The Experimental Man with David Ewing Duncan

Where: Atlas Cafe, 3049 20th St @ Alabama St.

When: Monday, October 19th 7-9 PM

Cost: FREE

Details: David Ewing Duncan discusses his new book “The Experimental Man”, his book exploring what cutting-edge technologies in personalized medicine can tell us about individual health and life — past, present and future: genes, environment, brain and body.

Could a genetic test have told me I was at a higher risk for developing type 2 diabetes? Image source: aldenchadwickThis sounds contrived but it isn't.  A couple of weeks ago I was diagnosed with metabolic syndrome.  Right when I am in the middle of talking about genetic testing!

Metabolic syndrome isn’t quite as scary as it sounds.  Basically I am on my way to type 2 diabetes.  But if I eat better and get off the couch, I should stave off the disease and get better.

My question, naturally, is whether or not a genetic test could have told me I was at a higher risk for developing type 2 diabetes.  And whether I would have done anything with that result.

As you know if you’ve been following my blog, I took a 23andMe genetic test and have been writing about it since.  The image below shows what the front page of my clinical report looks like (click to enlarge):

According to the DNA checked in this test, I am in the average risk range for type 2 diabetes.  This doesn’t really seem to line up with my reality.  But I might not expect it to since these genetic tests are so limited right now.

This kind of test can be informative with the yes answer—yes I carry a certain version of a gene that might lead to a disease.  But the no answer isn’t that useful.  It doesn’t mean that they've looked at all the possible genetic differences that can lead to a disease and I don’t have any of them.  Basically it means that they didn’t find the specific genetic difference they were looking for.

Now I wouldn’t necessarily have predicted that any genetic test available right now could tell me a lot more than that.  Type 2 diabetes is too complicated for that and a whole lot more research will need to be done to get a genetic test useful to lots of people.

But still, this is probably what people are looking for with these sorts of genetic tests.  Will I get cancer, type 2 diabetes, Alzheimer’s, Parkinson’s, etc.?  For most of these cases, the tests can tell you a lot about rare forms of these diseases but little about the more common forms.

So the no answer didn’t really help me much.  Here I am on my way to being a diabetic and the test said I was at average risk.  Of course, I suppose I didn’t even need to take a test… all four of my grandparents came down with type 2 diabetes.  Like lots of these complex diseases, family history is the best predictor.

The second part of my question is a hypothetical one.  Let’s say they had a perfect genetic test that said that I was at an increased risk for type 2 diabetes.  Would it have changed my behavior?  I’m not sure but probably not.

I certainly wouldn’t have changed any of my behaviors when I was young.  I was invincible, remember?

Now that I’m a bit older, such a test might have influenced my behavior a bit.  I already knew about my risk because of my grandparents but my thought has always been that maybe I got lucky and didn’t inherit their tendencies towards diabetes.  But if they were tested and we shared the same genetic differences that led to type 2 diabetes, then I might be worried enough to change what I was doing.

Most likely though, my behavior modification wouldn’t be perfect.  What I’d probably do is keep watching TV and eating Twinkies but get my blood sugar tested more often.  Once I was headed for diabetes, then I’d modify my behavior and keep it at bay.  (I’m sure doctors scream into their pillows at night because of patients like me.)

This is different than some people’s reactions to other genetic tests.  For example, some women who find out they have the version of BRCA1 that greatly increases their chances of breast and ovarian cancer have a double mastectomy and/or a hysterectomy before there are any signs of cancer.

I might react much more strongly with a valid cancer genetic test.  Cancer is scary, nasty and not really reversible.  Type 2 diabetes is different.  You can start down the road, modify your behavior and then nip it in the bud.  Carpe diem and then pay the piper.

Is corn ethanol a poor fit for future U.S. liquid fuel needs? Biofuels have received a tremendous amount of publicity lately as an alternative to gasoline and diesel. An ethanol economy based on sugarcane has helped to boost Brazil into the limelight, raising standards of living and perhaps even contributing to the country’s recent successful bid at the 2016 Olympic games. In the U.S. prospects of corn-based ethanol have piqued the interest of agriculture and oil companies alike. Such unbridled excitement has also revealed dramatic downsides. Brazilian affluence comes at the price of biodiversity as swaths of rainforest are sacrificed to plant new crop fields. Increased American deand for corn was a measurable contributing factor to the recent world food crisis.

The timing, then, was quite appropriate for a panel discussion last week organized by the Friends of Berkeley Lab at the Berkeley Repertory Theatre. Titled “Hope or Hype: What’s Next For Biofuels?” the event, hosted by KTVU’s John Fowler, featured a panel with Jay Keasling, Susanna Green Tringe, and Jim Bristow, three scientists exploring the role that synthetic biology might play in fabricating a better fuel for tomorrow’s autos. The evening consisted mainly of two themes: the relative limits of both crude oil and corn-based ethanol, and an outline of research being pursued to make new ideas practical.

Fossil fuels are unsustainable, a point that saturates public rhetoric each election cycle to the point of ad nauseum. It might be slightly more surprising to learn, however, that fuel based on ethanol (the alcohol found in all common beers, wines, and liquors) may be as bad for global warming as gasoline, perhaps even be worse. When extracted from corn, considerable energy is lost on fertilizers. If that energy was generated using a coal plant, global warming is still a problem. Additionally, ethanol is an unwieldy fuel. It is corrosive, for example, and therefore must be trucked, rather than piped, from one location to another. “I like to say that ethanol is for drinking, not for driving,” Keasling joked as he explained these faults.

The push in the American science community, then, tends to be away from corn-based ethanol and toward something called cellulosic biomass (Editor's Note: see our QUEST video "Beyond Biofuels" for more information). The idea is to make fuels not from corn, but rather from corn stover—plant leftovers after the crop has already been harvested. Alternatively, almost any other organic material ranging from wheat stover to sorghum to garbage could be used if the proper techniques are developed.

There are considerable scientific challenges. Much of the material we might like to use as fuel is tough and woody. Scientists have yet to figure out a satisfactory method for breaking this down, and a great deal of gene-sequencing effort is currently underway with the aim figuring this out. There are also challenges in terms of deciding what product will be generated from these woody materials. At least one idea is to genetically engineer an organism that can transform organic matter not into ethanol, but rather into something more amenable to transport and carbon neutrality.

What should we make of these new efforts? My own feelings are mixed. I enjoy my car, and I love road trips. As Bristow said during the panel, “The reality in the U.S. is that people are going to drive cars. We need liquid fuel.” The current push in biofuels research is tremendously important. The vast majority of energy sources are simply inadequate for powering cars to the extent that the public is accustomed to. The maximum power one could ever expect to obtain from a solar-powered car, for example, is less than 10 horsepower. Even the Geo Metro gets 55 horsepower. The new Volkswagen Beetle gets over 100 horsepower. Electric cars might hold some promise, but at this point it is impossible to tell whether batteries or biofuels will ultimately make a better alternative. These two fronts are also not necessarily exclusive, as the hybrid explosion of recent years has shown.

And yet, for all the excitement, selling the American public on biofuels feels a little like feeding methadone to a heroin addict. We believe that a shift to biofuels will assuage the continued seeping of carbon into the atmosphere. But there are a lot of side effects. The controlled production of biomass requires land, and with that allocation comes a host of ecological concerns. When it comes down to it, there will never be a substitute for good old fashioned belt-tightening.

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.