A Look Behind the Scenes of Your DNA Testing Kit

Walk down the health care aisles of your local Target (or Walgreens, Walmart, CVS Pharmacy, or Best Buy) and look through the shelves. You might come across a small white glossy box. It’ll have some rainbow-colored stripes at the bottom, a beckoning message written on the center, and a logo on the top corner: 23andMe.

23andMe is a genetic testing company that now reports having over 10 million customers. Their rising popularity can be credited in large part to their accessible direct-to-consumer services. Customers, instead of going through their doctors or professional health care providers to request a genetic test to learn more about their ancestry and health, can purchase their own tests online or in a store. The standard process currently takes about $200 and a few weeks wait.

The information the service puts together is pulled from your DNA. DNA, known as one of the most stable data storage systems on earth, is made up of strands of four types of molecules known as nucleotides – adenine, guanine, cytosine, thymine – that we refer to as A’s, T’s, G’s, C’s. The nucleotides are connected one after another in a purposeful order referred to as the DNA’s sequence. Two of these strands then come together and pair up, nucleotide by nucleotide, chemically bonding in specific pairs: A’s pair with T’s, and C’s pair with T’s.

Similar to how a computer’s binary code of 0s and 1s provides processing instructions, or how the alphabet’s letters form words and sentences in manuals, DNA’s quaternary code of four nucleotides string together to provide instructions for cells. Some of these instructions are for assembling proteins, the tiny biological machinery running the factory that is every cell. Other parts of DNA tell processes in the cell when to turn on or shut off. Each instruction is known as a gene, and is responsible for coding personal qualities visible on the surface – earlobes, eye color, hairline shape – and many things that aren’t visible either, like the amount of sleep someone needs every night, their skin’s ability to protect them from sun damage, or their chances of having certain cancers or Huntington’s Disease.

Ultimately, this means that DNA is the blueprint that makes you, you. If DNA can explain the nuts and bolts behind what you see in the mirror or, something even heavier to consider, the hidden diseases you could one day encounter, wouldn’t you want to be able to know and understand your DNA also?

How Do You “Read” DNA?

Just two decades ago, the Human Genome Project took researchers across the world 2.7 billion dollars and 13 years to sequence the 3.2 billion nucleotides of the human DNA sequence, known as the human genome. The scientists at the time had no reference sequence to guide them. They also had to break the genome apart into manageable fragments, figure out each fragment’s sequence, then piece everything back together at the end.

Since then, scientists have developed faster and more accurate ways to read, or sequence, DNA. This next generation of DNA sequencing technology is known as high throughput or massively parallel sequencing, meaning scientists can process many samples at the same time, or “in parallel.” For DNA, the term “many” can mean sequencing millions to billions of DNA sequence fragments all at once. 

Illumina, a San Diego-based biotechnology company, spearheaded this advancement by developing innovative sequencing machines and techniques that harness natural processes already occurring in biology. In every living cell, DNA must replicate itself to pass on genetic information to new cells. To synthesize new DNA, the two strands of DNA split into one. Then, a protein comes in and attaches to the DNA. The protein moves along the DNA, nucleotide by nucleotide, identifying each nucleotide so that it can attach the proper matching nucleotide to the new strand being built (A’s pair with T’s, C’s pair with T’s). The process is similar to adding beads along a string while following an instruction manual. In this case, the cellular machinery stringing nucleotides together knows exactly how to read the manual, rapidly and accurately.

Illumina repurposed this process into a method called sequencing by synthesis to read DNA. This method involves a small flat chip, varying in size depending on the scale of the machine, that catches single stranded DNA of unknown sequences when it flows over. The DNA is replicated, similar to the process described above that occurs in a living cell. However, instead of using normal nucleotides, scientists spike in nucleotides that fluorescently light up. As each nucleotide is matched and added in a process that resembles DNA synthesis and replication, the nucleotide will shine a fluorescent signal specific to its identity. The sequencing machine sees each fluorescent nucleotide light up and records the corresponding nucleotide identity. At the end, it spits out millions of DNA sequences in the form of A’s, T’s, C’s, and G’s.

23andMe uses a version of this technology to analyze the DNA samples customers send in through a method called genotyping. Instead of trying to sequence every customer’s entire genome, genotyping will focus on just a tiny fraction of the genome. The estimated difference of your DNA from one person to the next is less than 1%. As part of this 1%, in some specific locations, there are just single nucleotide differences known as single nucleotide polymorphisms (SNPs). Scientists previously discovered that SNPs could be associated with certain traits. Genotyping looks at those known locations, compares the SNPs, and pieces together information ranging from possible ancestry to health (some of which was previously covered).

Besides 23andMe, there are companies that can sequence an individual’s whole genome as well. The cost to sequence an entire human genome has dropped down to about $1000 per genome in recent years. One of the most well-known companies, Massachusetts-based Veritas Genetics, was the first to offer the whole genome sequencing price of $1000 along with a 12 to 16 week wait. Since then, they offer whole-genome sequencing services for an even lower price of $600. Their sequencing methods also rely on Illumina technology. In comparison to 23andMe and similar companies, Veritas Genetics looks for more information and provides the 99% of the human genome that 23andMe genotyping misses.

How do you understand DNA?

Whether genotyping or whole genome sequencing, or looking at 1% or 100% of the entire sequence, what can someone do with the information? Scientists continue to research how genes affect human traits and diseases in dedicated fields of genetics and genomics. As research develops, more details also emerge on how microbiomes, epigenetics, and environmental factors can play a factor in affecting our traits, personalities, and health.

Advances in DNA sequencing technology have made the growing popularity and accessibility of genetic testing possible. The success of these companies can be a positive reflection of the growing number of individuals who are aware of the connection between DNA, genetics, and the physical traits they manifest as. More people are taking action to understand their own biology, and these direct-to-consumer services often appear the closest achievable way. However, DNA sequencing technology is also growing faster than our ability to understand it, regulate it, and decide who else has access to it.

What do we do with genetic information? Who does it belong to? How do we responsibly act on this knowledge? We’ll be tackling these concepts in a part 2 of this series, so look out for more.

Luyi Cheng is a PhD candidate studying biology at Northwestern University.