The human genome is three billion bases (or the A/T/C/G “letters”) long. Not all genetic tests are created equal — and that’s because there’s lots of different ways to read your DNA. We’ll cover the basics of how different testing technologies work and how much DNA is analyzed by each test to give you a better understanding of what exactly you’re getting and at what price.

Orchid offers advanced genetic testing for couples who want their child to have the best shot of a healthy life. “Ask a Genetic Counselor” is where we unpack how genetics impacts our everyday lives and the latest tools to help you build a healthier family.  ‍

Overall landscape of genetic testing

When evaluating the cost of a genetic test, there are three main questions to ask:

1. What part and how much of the genome is being read? — This helps you understand how thorough and comprehensive a test is and how likely the results can provide answers to what you want to find out. 
2. How is the DNA being analyzed? — The two most common technologies used in genetic testing is genotyping and sequencing. Sequencing collects more information than genotyping, though tends to cost more. 
3. What expert consultation and support is included with the test, if any? — Access to genetic counseling and support can be invaluable to understand what your results mean to you and explore personalized next steps.

Here we’ll review types of commercially available tests using this framework of questions.

SNP genotyping array — 23andMe

What is analyzed

The DNA sequences of any two humans are 99.9% identical, but there are lots of places throughout the genome that aren’t identical between people. These places where we commonly find genetic variation are called SNPs, short for single nucleotide polymorphisms (pronounced like “snips”). SNPs are places where the DNA code, for example in some people is a “G” and for other people is a “T”. Depending on where these SNPs fall, they can cause differences in physical traits, how a person’s cells function, and even disease predisposition. As humans have evolved and spread all over the world, certain SNPs may be more or less common among different populations, making them good markers for assessing ancestry.

Services like 23andMe and Ancestry have curated lists of SNPs that they test for. These services don’t sequence the full genome, but rather test for 500,000-750,000 SNPs that are known to commonly differ in humans. That’s far less genetic data than the 3 billion data points present in every human.

Not all variation seen across humans is captured with these SNP microarrays, though. With a limited number of DNA markers to test for, the testing services need to determine ahead of time which markers to test for. That means that they can miss many important variants, like DNA markers that can lead to disease, such as thousands of BRCA1/2 breast cancer variants.

Handpicking only certain hotpots along the genome also means that services like 23andMe need to frequently update their tests to incorporate newly discovered variants that affect ancestry and health wellness traits. These are often referred to as different SNP microarrays, or “chip versions.” Therefore, a test purchased years ago that did not include those new variants may not let you benefit from new insights and redesigned tests.

How it's analyzed

A person’s DNA, usually collected from a saliva sample, is extracted from the cells in their sample. The DNA is processed on a device called a microarray, which has millions of tiny detectors that each give off a signal when they encounter a piece of DNA with the exact matching base letter that they test for.

So, SNP genotyping simply checks certain predetermined hotspots in the genome, which together only comprise less than 2% of your DNA.

Where the cost comes from

SNP-based genotyping is the least expensive type of genetic testing service currently available. This is because the genotyping array and other materials used to run the test are fairly inexpensive, and the raw test results can be delivered without the need for expert genetic interpretation or sophisticated statistical modeling. These services also don’t offer genetic counseling which some may find distressing, especially if you receive results you didn’t expect. If you want expert support, you’ll need to seek out a third-party service on your own.

This type of direct-to-consumer SNP testing typically runs $99-250, depending on the service, the number of variants tested for, and the types of variants being reported (only ancestry information or other health wellness traits included). We cover more about what 23andMe is best for and not a use case for in this article.

Whole genome sequencing — Orchid

What is analyzed

Whole genome sequencing provides information on over 99% of the genome. Instead of picking and choosing SNPs to test for, Orchid and other clinical-grade whole genome sequencing services read and get information on 3 billion DNA bases.

In addition, Orchid’s Couple Report offers whole genome sequencing for both partners, not just one person, to analyze how your combined genetics can influence your future child’s health.

Different services may provide whole genome sequencing at varying levels of coverage. Coverage refers to the number of times the DNA code is read. Multiple reads through the genome helps correct any errors introduced by the sequencer machines themselves and ensures that both copies of each chromosome are sequenced sufficiently. A higher coverage means that the sequence is read more times, allowing errors to be detected and corrected with higher confidence.

Low-coverage whole genome sequencing means every base in the genome is read several times over. With Orchid's genetic predisposition screening, certain parts of the genome are also imputed or computationally calculated based on the rest of the DNA sequence to ensure accuracy. That means if one particular DNA variant always occurs in the genomes of people with specific other variants, the one variant can be determined with even greater confidence.

Low-coverage whole genome sequencing combined with imputation has been shown to be an accurate and cost-effective way to measure genetic predispositions to common conditions.

High-coverage sequencing is when the genome is read on average 30 to over 100 times. This may be indicated for diagnostic testing (testing an individual affected by a condition) or to identify rare genetic mutations that can cause disease. However, the cost increases by severalfold compared to low-coverage sequencing.

Orchid provides both low-coverage and high-coverage whole genome sequencing depending on the test selected.

How it's analyzed

A person’s DNA, usually collected from a saliva sample, is extracted from the cells in their sample and chopped up into smaller pieces. The DNA pieces are loaded onto a sequencer machine, which reads out the full sequences of the chopped-up DNA. These “reads” are put back in the right order by computationally aligning them to a reference genome sequence. Any differences from the reference genome can be followed up for closer inspection by a statistical geneticist.

Where the cost comes from

The materials used in processing and sequencing the DNA samples are more specialized and more expensive than in genotyping. The sequencing machines are complex, expensive instruments with a limit to the number of samples that can be run simultaneously.

The cost of sequencing is usually correlated with the level of coverage. Low-coverage sequencing has much lower costs by allowing more tests to be run simultaneously on each sequencer machine, compared to high-coverage (30-100X) sequencing. The cost of each run (materials, machine cost, technician time) can be divided among more samples on low-coverage runs.

Orchid reports also come with a personalized video walking you through your results (not some sample report) from a board-certified genetic counselor. You also have the opportunity to ask questions and discuss one-on-one with a genetic counselor about your results at any time. Access to expert consultation and support is included with the report at no additional cost.

Targeted gene panels

What is analyzed

When a physician suspects a genetic cause for a rare genetic disorder based on personal or family history, or when a couple is discussing becoming pregnant, a genetic test for a panel of genes may be ordered.

These panels look at specific genes with a very high confidence to find any single gene mutations that can impact the health of an individual or their children. Different panels test different sets of genes. Examples can include gene panels for cancer susceptibility syndromes or carrier screening for rare genetic disorders like Tay Sachs.

How it's analyzed

A person’s DNA, usually collected from a blood or saliva sample, is extracted from the cells in their sample. Because a known panel of genes is being tested, only those genes are analyzed through genotyping or, more commonly nowadays, DNA sequencing.

Where the cost comes from

Gene panels are often ordered by a physician as a diagnostic test and cost of testing can be covered by some health insurance plans. Clinical testing labs such as Invitae, Natera, and Myriad offer access to speak with a genetic counselor to answer questions about test results at no additional charge. These panels can range anywhere from $250 to over $2,000.

Targeted sequencing-based tests look for mutations in only a small fraction of the whole genome. The typical cost is less than a whole genome sequencing test because much less DNA is sequenced in each test.

Some tests are also offered as proactive screening for individuals without health conditions. Orchid offers many gene panels for individuals and embryos using whole genome sequencing methods. Orchid's testing also offers access to speak with a genetic counselor at no additional charge.

Takeaways

• A variety of commercially available genetic tests are designed to return different results and answer different questions.
• When evaluating the cost of a genetic test, you should ask: what part and how much of the genome is being read? How is the DNA being analyzed? What expert consultation is included with the test, if any? 
• The right genetic test for you depends on what you want to find out — Are you and your partner planning on growing your family and want to minimize disease risks for your children? Does your family have a history of certain genetic disorders that your doctor wants to investigate? Do you want to explore your family’s ancestral roots?

Orchid offers advanced genetic testing for couples planning on building their family. We use advanced tools and smart, caring humans to help you give your future children the best shot of a healthy life. Conceive with greater confidence and peace of mind