DNA genotyping is currently one of the major types of DNA tests available from the direct-to-consumer DNA test kits like Ancestry.com and 23andMe.  If you’re interested in the three main types of DNA testing available, take a look at our overview of the different types of commonly available at-home DNA tests.  Let’s review how DNA genotyping works and assess the strengths and weaknesses of this commonly used type of genetic testing.

What is DNA genotyping?

DNA genotyping refers to a specific type of genetic test that evaluates for small changes in your DNA called single nucleotide polymorphisms.  Your DNA code is made up of four different nucleotides (reviewed in detail here), a change of one of these nucleotides is called a single nucleotide polymorphism or SNP.  An example of a SNP is a change from A to T at one position in your genome.  DNA genotyping looks for these small differences in your DNA and uses these changes to estimate your ethnicity and make predictions about certain types of traits or behaviors you might have.  Geneticists call the collection of someone’s DNA sequence their ‘genotype’.  A person’s genotype describes the collection of different nucleotides that make up a person’s genome.  DNA genotyping is a technique designed to read parts of your genotype by checking for SNPs within your genome.  Because some SNPs are more common in different populations, DNA genotyping can be used to understand your ethnicity and ancestry along with some genetic traits.

How does DNA genotyping work?

DNA genotyping works by printing different types of small DNA changes (SNPs) onto a piece of glass.  This piece of glass with the different DNA SNPs printed on it is called a “DNA microarray”.  DNA genotyping works because DNA is a double helix – if your DNA matches the SNP printed on the DNA microarray, it will attach to the glass slide and can be detected by glowing.  By printing many different DNA SNPs onto a glass slide, the DNA genotyping test can look at the presence or absence of many different kind of SNPs in your genome.  This picture below shows what a DNA microarray looks like when a person’s DNA has been added to the glass slide and starts to glow:

A DNA microarray used for DNA testing by companies like 23andMe and Ancestry.com

A DNA microarray similar to those used by 23andMe and AncestryDNA.  Each individual ‘dot’ is a probe that can look for one DNA change.  A modern DNA microarray can hold hundreds of thousands of spots – but cannot look for all possible changes in your DNA.  Credit: Guillaume Paumier

Each circle in the image above represents one type of SNP that is being tested on the DNA microarray.  This picture is really zoomed in – a single DNA microarray can hold hundreds of thousands of different SNPs.

Does DNA genotyping look at all my DNA?

No, DNA genotyping only looks at a small number of different parts of your DNA.  The most advanced DNA genotyping tests look at a small number of SNPs relative to the millions we have identified in people.  Many companies use a type of microarray purchased from Illumina called a “Beadchip” which can hold about four million different SNPs on each chip.  This seems like quite a few SNPs, but remember that there are 3.2 billion pieces of DNA in your genome – this means that a beadchip covers much, much less than 1% of your genome. In addition, because a genotyping test looks for specific DNA changes, those four million SNPs must be divided up across all the different possible changes.  In the end, DNA genotyping looks at a very small number of the possible changes that could happen in your DNA.  Because some of the DNA changes that cause genetic diseases are very rare, DNA genotyping is not a good test to run to test for genetic conditions.

How can DNA genotyping tell me about my ancestry and ethnicity?

DNA genotyping looks at the combination of small DNA changes in your genome called SNPs.  Because some SNPs are more prevalent in a certain ethnicity or geographic region, DNA genotyping can start to understand where parts of your DNA originated from.  A DNA ancestry and ethnicity test compares your combination of SNPs against different groups and calculates the percentage of your SNPs that are associated with each ancestral group.

Can DNA genotyping tell me about genetic disease?

DNA genotyping tests only look for the genetic changes that are printed onto the DNA microarray.  This means that the test is specific to changes that are already known.  The most advanced DNA genotype tests will look at DNA changes that are present in about 1 out of 100 people.  Genetic diseases can be caused by very rare changes that are present in 1/100,000 people or even rarer.  This means that DNA genotyping is not the right test to diagnose a medical condition.

Some companies have added specific DNA changes associated with genetic diseases like cystic fibrosis and breast cancer to their DNA chips, but these tests do not look at all of the possible changes that could cause cystic fibrosis or cancer.  That means that a negative DNA genotyping test does not mean that your DNA does not have a change that can cause cystic fibrosis or breast cancer.  The pie chart below shows the coverage of the 23andMe BRCA2 test (spoiler: It’s not good!)

BRCA2 variants covered by 23andMe DNA test kit using DNA genotyping

BRCA2 variants covered by the 23andMe DNA test kit.  There are at least 3,239 known cancer causing variants in the BRCA2 gene.  As of March 2018, 23andMe tests for only one.

Pathogenic variants in the BRCA2 gene cause a genetic disease called “Hereditary Breast and Ovarian Cancer Syndrome”.  Geneticists have identified 3,239 different ways for BRCA2 to break and cause cancer.  23andMe tests for only one of these 3,239 different known variants, meaning that a negative 23andMe test is not truly negative!

Because DNA genotyping is not a comprehensive test, it is not recommended for use in medical genetics.  If you are concerned about a genetic disorder, consult your health care professional for referral to clinical genetic testing.


Previous articlePhenylketonuria: A disease of phenylalanine metabolism
Drew Michael, Ph.D.
Dr. Drew Michael is a Clinical Molecular Geneticist and Clinical Biochemical Genetics fellow. He holds a Ph.D. in Molecular Cell Biology and an M.S. in Biochemistry and Molecular Biology. Dr. Michael has an extensive background in molecular and computational genomics and runs a research program designed to understand the gene regulatory programs which control human development and disease. His diagnostic research is focused on the molecular and biochemical diagnosis of rare human diseases. Outside of science and medicine, he really likes dogs and lives in Washington, D.C. with two german shepherds.