In the last 10 years, massive advances in molecular biology and genetics have unlocked the human genome.  Sequencing the first human genome cost the U.S. National Institutes of Health 2.7 billion dollars and decades of time – in 2018 it only takes a few days and 850 dollars to sequence a human genome.  Let’s take a brief look at the different technologies that can be used to understand your DNA.

What are the main types of DNA testing technologies?

There are three main types of DNA testing technologies that are used in modern genetic testing:

  1. Next Generation Sequencing (NGS): This type of test is the newest and most advanced DNA test that is currently available. Next generation sequencing can look at just one DNA change or examine all of a person’s DNA.  This price of this test can range from $200 to over $10,000.  Many of the modern clinical genetics assays use this type of genetic test.
  2. DNA genotyping: This is an older type of test that was invented in the late 1990’s. In DNA genotyping, only a small part of the genome is analyzed but many different changes can be checked at once.  This type of testing is typically used in direct-to-consumer tests run at companies like 23andMe and Ancestry.com.
  3. STR analysis: STR tests are one of the oldest types of genetic testing and are also called “DNA fingerprinting”. STR profiling looks at a small number of different sites in your DNA and is used in DNA forensics and paternity testing.

What is the difference between DNA sequencing and DNA genotyping? 

In DNA sequencing, a test is run that amplifies and then “reads” your DNA code (look here for a review of what DNA is and how the DNA code works).  This type of test can detect many different types of DNA changes, even changes that are completely new and have never been seen before.  Because there are many rare changes associated with human genetic diseases, this type of testing is very useful in clinical genetics because it reports on many of the possible DNA changes that could cause disease.

DNA genotyping is a different type of testing that only looks at certain, pre-specified changes.  This means that the test will not find new DNA variants that have never been seen before.  These tests can test about a million different variants in one step – but there are millions of changes in your genome and an almost infinite number of changes that could occur.  DNA genotyping tests will often only look at common variants or variants that are associated with disease or a trait.  Because DNA genotyping based tests do not look at all possible DNA changes, they are not a conclusive form of testing for most genetic conditions.

Why is DNA testing getting so cheap?

The shortest answer is that new technologies have been developed that analyze your DNA in many small pieces all at once.  This approach is different from earlier types of DNA testing which examined the genome one part at a time.  The change in the cost of DNA sequencing is best demonstrated in the plot below:

The impact of next generation sequencing costs on whole genome sequencing and DNA testing.

NIH/NHGRI cost of whole human genome sequencing over time. The white line shows the advancement of computer technology predicted by Moore’s law.  DNA sequencing is advancing faster than computer technology.  The cost drop in 2008 is from the development of next generation DNA sequencing. Data and plot generated by the NIH/NHGRI.

What a change! Look at the Y-axis of the plot and see that it is in a logarithmic scale that is changing by a factor of 10 for each step.  The white line labeled as Moore’s law describes the rate at which computer technology is advancing.  Amazingly, DNA testing technology is advancing even faster than computing technology.  The drop in price that occurred around 2008 is from the development of the “next generation sequencing systems.

I acquired the data and plot from the fantastic NIH/NHGRI sequencing cost page which is definitely worth a look if you want to learn more about current NGS costs.

If next generation sequencing is so great and cheap, why do companies like 23andMe and Ancestry.com use DNA genotyping instead of sequencing?

Great question – you’ll have to ask them for a definitive answer.  Generally, it comes down to legacy technology investments and economies of scale.  The direct-to-consumer (DTC) companies have been using DNA genotyping for years now and have built databases of hundreds of thousands of people who have been tested.  It is easier and cheaper for these companies to use the older genotyping based tests because they don’t have to change their laboratory workflows and can easily compare new data with old data.  Many of the newer DTC companies have switched over to using next-generation sequencing for their tests.  If you opt-in to research at 23andMe, the company may sequence your genome using next generation sequencing.  Carefully consider the privacy implications of any genetic test you decide to run.

It costs $850 dollars to sequence a genome, but a clinical DNA test can cost thousands of dollars. Why?

The main reason for this difference in price is the cost of analyzing and interpreting the DNA test.  It costs $850 to sequence your whole genome but then someone has to go through the results and figure out what all the changes mean.  In whole genome sequencing, there will be about 4,500,000 changes detected in your genome!  This is a huge amount of information to process and most labs will analyze the information using supercomputers and doctors trained in Clinical Molecular Genetics.  It can cost thousands of dollars in time and labor to analyze a genome and this adds to the price.  In the case of clinical genetics, mistakes cannot be tolerated so an additional cost is added to allow for multiple reviews by different doctors.

Conclusions:

We’ve talked a bit about the three different types of DNA testing.  For a review of DNA fundaments and how DNA functions – take a look at the post “What is DNA?”.  If you’d like to know more, consider the things you should know about clinical genetics DNA testing and direct-to-consumer test kits like 23andMe and Ancestry.com’s AncestryDNA.