Autosomal testing vs Mitochondrial testing (mtDNA) vs Y-Chromosome testing

When going over your options for a direct-to-consumer DNA test, the options can be overwhelming. Between the different companies available, testing methods used, and services provided, it can be hard to choose a company and plan with any confidence. In terms of testing methods alone, there are several approaches different companies take to analyze your genetics. In general, companies tend to analyze up to 3 different parts of your genetic code. The majority of companies test your Autosomal Chromosomes. These chromosomes represent a majority of your DNA. They account for 22 of the 23 chromosomes.

The 23 chromosome is your Sex Chromosome, and contains two forms: X and Y. Females have a pair of X chromosomes, while men have an X and a Y. Because the Y is always passed down from the father, scientists can use genetic markers on the Y chromosome to better understand a person’s ancestry on their father’s side. Because both males and females carry an X chromosome, a maternal line cannot be interpreted by studying the X chromosome alone. In fact, many companies analyze the X chromosome with the rest of the autosomal chromosomes.

Instead, laboratories turn to Mitochondrial DNA (mtDNA). This form of DNA resides within your mitochondria, tiny organelles which produce energy for your body. These organelles are only passed on through an ovum, or egg. Thus, your mtDNA testing comes only from your mother and your grandmother. Scientists can use mtDNA to study your maternal ancestry.

Which Methods are the Most Accurate?

Though this is a simple question, it is a complicated answer with several parts. In the broadest sense, all three of the above testing methods are just as valid as the next. These three “methods” simply refer to testing different parts of the DNA code. However, how that code is tested is fairly similar among all DNA testing companies.

To test large quantities of DNA quickly, a laboratory cannot “read” every single sequence in the DNA. Human DNA contains approximately 3 billion individual nucleotide base pairs. To accurately read and identify each one of these would take far too long.

Instead, laboratories commonly look for SNPs, or single nucleotide polymorphisms. While the majority of your DNA is identical to almost everyone else, small parts of some genes have developed mutations and changes over time. These changes are often only a single nucleotide pair in the code of over 3 billion. However, a gene with several unique SNPs can be positively identified as one of several alleles (or versions) of the gene. Different alleles function differently, producing slightly different proteins which can affect the functions of your cells or body as a whole.

To identify these SNPs, laboratories use SNP chips. These small devices can test large amounts of DNA for specific SNP sequences. If an SNP is found, it is bound and identified by computer scans. These chips can contain the information for hundreds of thousands of SNPs. The more SNPs a chip contains, the more SNPs per gene, and the higher the chances of a true-positive. A false positive may occur if a company does not use enough SNPs to identify a specific allele.

Below is a chart with several major genetic testing companies, the SNP chip they use, and the number of SNPs they test for. This data was compiled from the International Society of Genetic Genealogy Wiki.

At first glance, you will notice that all of the major companies use SNP chips from the same source: Illumina. Many of these companies have customized chips from Illumina, which search for different SNPs than their competitors. While it may seem like a huge variety in the amount of SNPs tested, in the context of billions of nucleotide pairs, the difference between companies is not that much.

You will also notice that some companies test only autosomal DNA. While this does not necessarily make them less accurate, much can be gleaned from mitochondrial DNA and Y-chromosome DNA. These sources of DNA change relatively slowly over time, and can be linked to large movements of the human population, known as haplogroups.

That being said, National Geographic’s Genographic Project Geno will likely be one of the most accurate and comprehensive tests provided. Not only do they test the most autosomal SNPs, they also test the most mtDNA SNPs and Y-DNA SNPs. This will likely provide the most complete view of your DNA. 23andMe would take a strong second, with Ancentry.com coming in a tight third. Remember, as companies update their chip technology and the speed of processing DNA increases, tests are likely to become much more accurate.

What Can DNA Testing Results Tell Me?

More important than how many SNPs a company tests for are the scientific validity of the results they present. For instance, being a carrier of the cystic fibrosis gene is readily testable, and is valid if the testing company uses enough SNPs to identify the gene. However, if a company suggests that you eat a certain type of cheese based on your “genetic profile”, the scientific evidence is lacking.

In fact the guidelines for so-called Nutrigenomics, or diet-advice based on your genetics, is still in its infancy. The industry is currently regulated largely by internal guidelines set within the companies themselves. Still other scientists have criticized the industry for not following rigorous enough testing practices to be meaningful. One study found at least a 40% error rate in false-positive reporting.

This means that 40% of the time companies reported patient’s having an allele which they did not. The authors of the study emphasize confirming your results with your doctor in a more clinical and rigorous environment. This is especially true in cases which may affect your health.

That being said, the FDA (Food and Drug Administration) has authorized the use of these tests for diseases like Parkinson’s, Alzheimer’s, Celiac disease, and others which may have a genetic component. While this does increase confidence in some companies testing methods, remember that the results of a Direct-to-Consumer genetic test can be highly flawed. Any actual medical genetic advice should be sought through a healthcare provider.

The CDC (Center for Disease Control) also provides an import resource for determining the validity of genetic test results. In their Public Health Genomics Knowledge Base they have ranked and sorted various genetic conditions with their scientific validity. Diseases like cystic fibrosis and ovarian cancer, which have clear and testable genetic components, are ranked Tier 1.

Tier 2 is reserved for conditions which have links to certain genes, but the evidence is not clear. Many conditions fall into this category, such as acne, an overactive bladder, and arthritis. While these disease may have been linked to some genes, there is no clear evidence linking these diseases solely to genetics. Often, companies will include these tests in a genetic evaluation regardless of their lack of scientific rigor.

Tier 3 is reserved for the least supported tests. This includes tests for things like depression, diabetes, and disease resistance to common disease. While scientists have identified some links between genetics and these areas, there is really no evidence linking these ailments to genetics. For instance, hereditary breast and ovarian cancer tests via genetic screening is in Tier 3. While your personal genetics can play a role in cancer, checking your genetics is not a safe method of screening for cancer. You should still receive regular health checks from your doctor.

So, Should I Get a Direct-to-Consumer DNA Test?

 If you want to know more about your personal genetics, and have familiarized yourself with the current limitations of genetic testing, go for it!

Just remember, not all tests are accurate or valid. Any company may present you with dire or dramatic results. Use resources like the CDC and FDA to judge the validity of the tests you are receiving. If you are concerned about your results, consult a doctor. Further, remember that your genes are only a simple blueprint. More and more, scientists are coming to understand that genetics are only one part of health. The other part is lifestyle, diet, and exercise. These components of your life play an equal, if not greater role in your overall health.

References

• Commissioner, O. of the. (n.d.). Press Announcements – FDA allows marketing of first direct-to-   consumer tests that provide genetic risk information for certain conditions [WebContent].     Retrieved December 4, 2018, from                 https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm551185.htm
• Grimaldi et al. – 2017 – Proposed guidelines to evaluate scientific validit.pdf. (n.d.). Retrieved from                 https://genesandnutrition.biomedcentral.com/track/pdf/10.1186/s12263-017-0584-0
• Grimaldi, K. A., van Ommen, B., Ordovas, J. M., Parnell, L. D., Mathers, J. C., Bendik, I., … Bouwman, J.       (2017). Proposed guidelines to evaluate scientific validity and evidence for genotype-based         dietary advice. Genes & Nutrition, 12(1). https://doi.org/10.1186/s12263-017-0584-0
• Tandy-Connor, S., Guiltinan, J., Krempely, K., LaDuca, H., Reineke, P., Gutierrez, S., … Tippin Davis, B.         (2018). False-positive results released by direct-to-consumer genetic tests highlight the             importance of clinical confirmation testing for appropriate patient care. Genetics in Medicine.            https://doi.org/10.1038/gim.2018.38
• Tier Table Database|Search|PHGKB. (n.d.). Retrieved December 4, 2018, from                 https://phgkb.cdc.gov/PHGKB/topicFinder.action?Mysubmit=init&query=all