23andMe's DNA testing was always fun. Now it is more useful as well.

As anyone who follows this blog knows, I had my DNA tested awhile back by a company called 23andMe.  I wrote about what I learned and didn’t learn from their testing in a bunch of blog entries.

In my mind 23andMe has always been a sort of recreational genetics testing company.  You can find out about your earwax, whether you are likely to have blue eyes or be lactose intolerant and lots of other minor sorts of traits.  This is stuff you probably already know but for geeks it is pretty cool to see them written out in their DNA.

The company always offered some health data too but it wasn’t that strong.  For example, they could tell you if you carried the most common DNA difference that could lead to cystic fibrosis (CF) but not about the less common ones.  In fact, I gave them an incomplete for their carrier testing a few months back.

Since then, the company has gone away from being a place where you get your DNA tested for coolness’ sake to one with a focus on health and/or ancestry.  With this change has come a much-improved product for people interested in what their DNA tells them about their carrier status for a variety of genetic diseases.

Carrier status is important if you are considering having a child.  If you and your partner both carry the broken versions of a gene that could lead to a disease, then your child would be at an increased risk for getting that disease.  For example, if both you and your partner have a nonworking copy of the CFTR gene, then, depending on the exact DNA you each have, your child could have up to a 25% chance of ending up with CF.

This is why the first iteration of 23andMe carrier testing wasn’t as useful as I would have liked.  They tested only one of the 100’s of different DNA variants in the CFTR gene that can lead to CF. Since this DNA variant only accounts for about half the cases of CF, there was a good chance that something would get missed.  This is no longer true.

As part of the refocusing, 23andMe looks for 31 different variants in the CFTR gene that are known to cause CF. Now this isn’t hundreds but is more than the 23 recommended by the American College of Medical Genetics.  And in fact 23andMe includes these 23 in the 31 it tests.

Of course the testing still isn’t perfect but no testing is.  Some of the tests are only useful for certain ethnic groups.  And there is no upfront genetic counseling to help you decide whether or not genetic testing would be useful in your situation anyway.

But the bottom line is that 23andMe’s testing for genetic diseases that you might be carrying is much stronger than it was before.  So much so that it can even give you some piece of mind for many of these diseases.

In some ways I’ll miss the more whimsical look at DNA that 23andMe used to represent.  But this obviously wasn’t a good business model for anyone except those enamored of DNA.  And 23andMe does need to make a profit…

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…

Human and chimpanzee chromosomes are very similar.
Note that human chromosome 2 is very similar to a
fusion of two chimpanzee chromosomes.

For the last few weeks I have been corresponding with someone about intelligent design (ID). More specifically, we have been chatting about why humans have 46 chromosomes and most of the great apes have 48.

To me, this is great evidence for evolution. Why? Because if you look at the chromosomes closely, you can see that human chromosome 2 is really just a fusion of two great ape chromosomes.

The idea is that a few million years ago, a common human-chimpanzee ancestor of ours had two of his or her chromosomes fused together. This sort of thing happens all the time even today. Around 1 in 1000 live births has one of these kinds of fusions.

Then, probably through chance,this ancestor with the fused chromosomes went on to found the human race. Now people have 46 chromosomes and chimpanzees have 48.

An alternative explanation is that the designers fused the two chromosomes together when they created humans. The idea would be that the designer wouldn't create every plant, animal, bacteria, and virus from scratch–why reinvent the wheel every time? Instead the designers would mix and match parts that worked.

So as part of the process of designing a human, the designer fused two ape chromosomes together. This would presumably be simpler than creating a human chromosome 2 the way the other chromosomes were made.

The difficulty with this idea is that there is no obvious advantage to having 46 chromosomes instead of 48. What matters is our DNA, not how it happens to be packaged.

It is possible that there was some advantage to fusing the chromosomes together. For example, maybe a new gene was created at the fusion point. Or maybe genes that were shut off before were now turned on in the new fused chromosomes.

There isn't any evidence of these kinds of things. And even if there were, a designer who can easily put in the 60 million or so differences between humans and chimpanzees should be able to accomplish whatever results a chromosome fusion gives more elegantly than sticking two ape chromosomes together.

Also, when you look at the fusion point, you can see that the DNA isn't exactly what you would expect if a fusion happened in the last 10,000 or even 100,000 years. The results look more like an event that happened millions of years ago.

The ends of a chromosome have a defined sequence of DNA repeats called a telomere. The DNA at the fusion point looks very similar to a string of telomeres (as we would expect from a fusion) but it isn't perfect. This is just what you would expect if the fusion happened millions of years ago. Because our DNA gets changed a little all of the time.

The environment or even our own cells can cause the wrong letter to end up in our DNA. Our cells are pretty good at fixing these mistakes but they don't catch them all. What this means is that our DNA builds up mutations over time.

When an unfixed change happens in a sperm or egg, then it is passed down to the next generation. If the changes that aren't fixed happen somewhere important, then they are selected for or against. But if they're neutral, then they just build up over time. Scientists can even use these sorts of errors to predict how long ago something happened. Or to trace human migration patterns.

These DNA changes at the fusion point do not fit with ID if they don't serve a purpose. Otherwise, why put them there? It will be interesting to see the results of experiments that might show if these sequences matter or not.

Dr. Barry Starr is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA.