Genetic Testing

I have no information about the genetic background of my father as he was adopted and does not know how to obtain his birth records because the hospital where he was born at no longer exists. I have two questions - one, can I get a full genetic profile of myself without my father's genetic history, and two, if so, where do I get this done? I want to find out my health risks and each individual gene I possess, so how can I do this?

-A high school student from California

December 2, 2009

You can certainly get a readout of your DNA from many different companies. And you don't need to know your dad's family history to get this.

But this isn't really the genetic profile you're looking for. What you want is for someone to look at your DNA and tell you your chances for getting sick. This is a more challenging job.

DNA profiles can be pretty good at figuring out your chances of getting certain diseases. For example, some companies are really good at finding DNA differences that can lead to diseases like cystic fibrosis or Huntington's disease.

Other companies aren't as good. They can only give you part of the story.

And no company can use your DNA alone to tell you much about your risks for a heart attack. Or common forms of cancers or Alzheimer's. Scientists just don't have a good grasp on what parts of our DNA are involved in these diseases yet.

To really figure out the odds of getting these diseases, you need a good family history to go with the DNA results. So genetic tests won't be as useful to you without your dad's information.

Still, DNA tests can definitely tell you a lot. They just won't be able to tell you everything.

What I thought I'd do for the rest of the answer is talk a bit about how DNA differences can lead to disease. I think you'll see why going from DNA to disease can be so tricky.

Then I'll go over the different companies that do testing and the different ways they look at your DNA. I'll try to bring up the plusses and minuses of each approach. And why genetic profiles aren't terrific yet for the more common diseases. 

DNA and Disease

Let's start with DNA. Your DNA has many of the instructions for making you. It has information on how you look, how your body works, how you act, and even how likely you are to get certain illnesses. Your DNA isn't the whole story, but a lot of who you are can be found there.

Like the instructions you're used to, DNA has its own alphabet. For something as complicated as a person, our DNA alphabet is incredibly simple. It has only 4 letters -- A, C, G, and T.

But the instructions themselves are very long. The human instruction book consists of 6 billion letters all in a certain order.

Most humans have a lot of this DNA in common. After all, we all need two arms, two legs, a big brain, etc. What makes each of us unique is that one out of every 1000 letters or so is different.

This translates to around 6 million differences. Scientists call these single nucleotide polymorphisms, or SNPs.

It is these differences that are responsible for my having blue eyes and you having brown. Or for why my kids might get cystic fibrosis and yours won't. As the last example shows, scientists can look at these SNPs and start to make predictions about how likely you or your children are to get a disease.

SNPs can't predict everything because, well, we don't know everything yet. And for lots of diseases like diabetes or cancer, DNA is only part of the story. Your lifestyle and the environment can play big roles too.

But still, a look at your SNPs can tell you something. We just have to be careful to understand what the various tests can and can't tell you. 

Genotyping: Looking at Some of Your DNA Differences

Genotyping is a way of reading DNA to determine a person's genetic traits. Basically scientists pick and choose from parts of human DNA that tend to be different. By looking at these selected SNPs, they can tell us something about our disease risk, ancestry, traits, etc.

Several companies use this method to look at over half a million of these small DNA differences all at once. The companies that use this method include: 23andMeNavigenics, and deCODEMe.

Half a million sounds like a lot but it really isn't -- it's only a small fraction of your total DNA. So you're really only getting a peek.

And just peeking at your DNA has consequences. You tend to get a pretty incomplete look at your DNA because there's a lot of information in our DNA that the companies aren't exploring. This can cause you to jump to the wrong conclusion based on your test results. Let's take cystic fibrosis (CF) as an example.

23andMe has a DNA test that looks for a certain SNP known to cause CF. If the test comes back negative, that means you don't have the SNP. So are you off the hook, right? No.

The SNP the company tests for is responsible for only around 70% of CF cases. The test result you got back says nothing about whether or not you have the any of other SNPs that cause the other 30% of CF cases. All you can conclude is that you don't have the most common SNP associated with CF.

This sort of thing happens with other diseases too. And is especially a problem for many common diseases that have many different SNPs all contributing to the risks for the same disease.

For example, the risks for developing type 2 diabetes are due to multiple SNPs spread out across our DNA. Since we don't know what all of these SNPs are, these genotyping companies undoubtedly miss some of them.

So any result you get about these types of illnesses will be incomplete. You may not have the SNPs they look for but still be at a high risk for type 2 diabetes.

For genotyping companies, a positive result can give you some information about a health risk. A negative result often tells you very little.

A better way to do a genetic test would be to get a full readout of all your DNA. Then you wouldn't leave anything out. But you might suffer from information overload. 

Sequencing: Looking at All of Your DNA

DNA sequencing is a way to read most of the letters in your DNA in the order that they appear. If your DNA (or genome) is a book, then DNA sequencing is like reading a book from cover to cover.

This is a very powerful method, since all of your DNA (and all of the small differences) can be read. The technology that does this is still very new, so it takes a lot of time and costs a lot of money.

A couple of companies will sequence your genome and give you a chance to talk to a geneticist about the results. These companies are called Knome and Illumina, Inc. This service is impressive, but very expensive (from $25,000 to $100,000!).

Knowing about all of your DNA obviously solves some of the problems with genotyping. But it introduces new ones too.

Let's use CF as an example again. Sequencing will allow us to catch all of the known SNPs that cause CF. But it will also find differences that scientists haven't seen before. Will that difference lead to CF? No one knows (at least not yet).

There are also SNPs that only cause CF some of the time. When you get a result back with that SNP you don't know what the result means. But if you're anything like me, you will definitely worry about it. A lot.

So even though we can get the entire DNA sequence, we still don't know what a lot of it means. In other words, our DNA book (our genetic code) is written in an ancient language.

Scientists in the past and present are working hard to crack the code but they're not there yet. Right now, most of our DNA is gibberish. 

Genetic profiles today What this all means is that even if we have all of the letters of our DNA, we still may not be able to accurately predict our chances for getting sick. This is especially true of the more common, complicated diseases.

For these diseases, genes aren't the whole story. How you live your life plays a big role as does how and where you were raised.

The bottom line is that for right now, genetic profiles can give us some information about our risk for developing certain diseases. But they can't yet tell us the whole story. And they may never be able to.

By Karen Colbert, Stanford University

A good family history is important for predicting the risk of getting many common diseases.

Our DNA is made up of four letters-A, C, G, and T.









Scientists use DNA chips to genotype DNA.













Scientists can't quite understand what human DNA says yet.