What type of DNA test is best for medical conditions?

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When it comes to DNA analysis technologies, Genotyping is an inferior technology for diagnosing genetic disease. Sequencing is the best way to properly understand your risk.

Sequencing and Genotyping are two methods for looking at your genetic code. Both make use of the latest technologies from companies like Affymetrix, Illumina, and Pacific Biosciences, yet there are major differences in how these technologies look at the genome.

A Quick Genetics 101

You can skip this section if you are already familiar with chromosomes, genes, exons, and mutations. What follows will be a quick “Genetics 101”.

Most of the DNA in your body is organized into 23 pairs of chromosomes. Half of this DNA comes from your mother, and the other half comes from your father.

  1. A chromosome is made up of nucleic acids (As, Ts, Cs, and Gs), which are otherwise known as nucleotides. To better understand scale, know that human chromosome 1 is made of over 249 million nucleotides!

  2. A gene is a specific segment of a chromosome that contains the instructions for how to make a specific protein in your body.

  3. An exon is a specific segment within a gene that is turned into a protein (some segments are skipped - these are called introns).

  4. A mutation is a change in one of the nucleotides within a gene that results in the production of a broken protein.

The purpose of a genetic test is to look within specific genes for mutations known to produce broken proteins. Continuing below is a discussion on Genotyping versus Sequencing, the two dominant methods for analyzing DNA.

How does Genotyping work?

Genotyping looks at Single Nucleotide Polymorphisms (SNPs), or single point mutations, throughout the genome. It is the technology used by a number of the consumer genetics companies including 23andMe, Ancestry, and many more. It is a cheaper technology than sequencing for a reason: genotyping only looks at a reduced set of specific, pre-defined mutations and is limited to that content alone.


Genes can be very long and contain many thousands of nucleotides. Mutations in many of these nucleotides might be responsible for disease. As an example, BRCA1 (which is known to cause inherited breast and ovarian cancer syndrome) is located on the 17th chromosome from position 41,196,312 to position 41,277,500. That makes the BRCA1 gene 87,188 nucleotides long.


Only a subset of the gene is responsible for forming the protein - the exons. In the BRCA1 gene, there are 24 exons spanning a total of 5,655 nucleotides. While mutations that cause disease exist outside of these exons, the vast majority of disease-causing mutations lie within the nucleotides of the exons.

The goal of a genetic test for the BRCA1 gene is to identify whether or not any nucleotides within the exons might be mutated, therefore causing disease. For a Genotyping test, targeting every nucleotide is not feasible. Therefore, the designers of a Genotyping test must select specific nucleotides to look for ahead of time.

As an example, the 23andMe test looks at only two mutations within the BRCA1 gene:

  • 185delAG (a deletion of AG located in Exon 2)

  • 5382insC (an insertion of a C located in Exon 20)

This means that out of the 5,655 nucleotides of the BRCA1 gene that help form its protein, 23andMe analyzes two.

It is fair to note that these two mutations are the most common mutations that cause inherited breast and ovarian cancer syndrome within the Ashkenazi Jewish population. That being said, while they are seen in 2% of the Ashkenazi Jewish population, testing negative for these mutations provides little to no information about disease risk for someone without that specific background.

There are many more mutations that have already been identified within the BRCA1 gene. ClinVar, the national public database used by laboratories to submit and review variations found across the genome, has seen 3,228 different reports of pathogenic mutations across the gene as of the writing of this article. Looking at only 2 mutations is truly just the tip of the iceberg.

How does Sequencing work?

Whereas Genotyping entails targeting specific nucleotides within a gene, Sequencing technology allows us to read long, continuous segments of a gene - often up to hundreds, or even thousands, of nucleotides in a row.


Within the example of the BRCA1 gene, sequencing can be used to target all of the 5,655 nucleotides within the exons of the gene (thus capturing the many mutations that have been previously reported in ClinVar).

When it comes to detecting disease, sequencing provides significantly greater coverage than genotyping ever could. The mutations that might cause BRCA1-related breast and ovarian cancer syndromes differ between ethnicities, families, and individuals. Only Sequencing has the opportunity to detect the variety of mutations that truly exists in our population.

23andMe, BRCA and Medical Genetics

The 23andMe test is a wonderful tool for learning about your ancestry and browsing certain traits about yourself. However, due to its use of Genotyping technology, the test generally only looks for a small subset of known mutations in any of the health-related conditions tested, similar to the analysis of BRCA1 in this post. After announcing the announcement of the 23andMe BRCA1 test, even the National Society of Genetic Counselors (NSGC) came out with a response, reminding anyone tested that only 3 mutations (across BRCA1 and BRCA2) are tested, and follow-up with a professional for a real, medical evaluation of risk is always needed.

Discussion in the New York Time

More recently, the editors of the New York Times published an opinion piece about Why You Should Be Careful About 23andMe’s Health Test. They discuss in detail the concepts addressed in this article and the shortcomings of a genotyping test in detecting a disease like Inherited Breast and Ovarian Cancer Syndrome.

Key Takeaways

Genomics is a really powerful tool. It can be fun, but it can also have life-changing information. When it comes to medical genetics (and the genetics of your health), make sure that the genetic test you use employs Sequencing technology.

Interested in learning more about PhosphorusONE and how your DNA can be used to prevent disease and live a healthier life?


The opinions expressed in this article are intended to bring to light recent scientific literature, technology advancements, and ongoing research as it pertains to genetic testing. They are the opinions of the author and do not necessarily represent the opinions of Phosphorus. This article is for informational purposes only, and is meant to induce conversation. To the extent that medical practitioners may provide input, or have written all or part of this article, this article is not, nor is it meant to be, a substitute for professional medical advice, diagnosis, or treatment.

Alexander Bisignano