Genetic testing has never been easier. At-home DNA testing services continue to grow in popularity as ways to learn more about your ancestry and inherited traits. However, sifting through all of the companies and DNA testing types to find the best DNA test can be overwhelming. Here, we give you a brief overview of the different types of DNA tests.
DNA Testing Technologies
DNA microarrays and Next Generation Sequencing (NGS) are two different technologies commonly used for genetic testing. Both can be used to read out genetic information from chromosomal and mitochondrial DNA. However, DNA microarrays and NGS technologies work very differently.
DNA Microarray-based Genotyping
DNA microarrays read out DNA at a defined set of positions that are known to vary between people. These positions are called Single Nucleotide Polymorphisms (SNPs). Most genetic testing services, such as 23andMe and AncestryDNA, use DNA microarray technology to profile (genotype) your genome at ~ 500,000 positions. This is less than 0.1% of the whole human genome. While microarray-based genotyping is very affordable, it misses a lot of important information.
Next Generation Sequencing
Next Generation Sequencing (NGS) is a technology that enables reading large amounts of genetic information very efficiently. NGS works by reading many small stretches of DNA and then piecing them together to determine a continuous sequence (Figure 1). In contrast to DNA microarrays, NGS can be used to read out entire genomes instead of just a small number of positions. However, while NGS produces much more data than microarray-based genotyping it tends to be more expensive. There exist several NGS-based DNA tests that have different price points.
Figure 1. Next Generation Sequencing (NGS). Image Courtesy of National Human Genome Research Institute.
NGS-based DNA Tests
Whole Genome Sequencing (WGS)
NGS technology can be used to read out an entire human genome. This is referred to as Whole Genome Sequencing (WGS). It enables unbiased, comprehensive discovery of genetic variants and yields deeper insight into personal genetic makeup. In addition to reading the entire genome, each position is often read many times in order to increase result accuracy. For example, WGS is typically done at 30x coverage (depth) which means that on average each position in the genome is read 30 times. This makes WGS much more expensive than microarray-based genotyping. However, NGS-based genetic testing can be made more affordable by sequencing only parts of the genome or by decreasing the number of times that each position is sequenced.
Whole Exome Sequencing (WES)
Whole Exome Sequencing (WES) reads out the ~ 1.5% of the human genome that encode proteins – molecular machines that perform most of the cellular functions. Because WES covers only a small portion of a human genome it is cheaper than WGS. However, WES misses genetic variants that are outside protein-coding regions and often have important regulatory functions. Furthermore, Whole Exome Sequencing is still quite expensive when compared to microarray-based genotyping. Thus, our answer to the question of whether to choose Whole Genome Sequencing vs Whole Exome Sequencing is to go with Whole Genome Sequencing.
An alternative to lowering the costs of NGS is to reduce the average coverage per position. Nebula Genomics offers low-coverage WGS at a cost that is comparable to genetic tests that use microarray-based genotyping. We sequence your genome at 0.4x coverage which corresponds to ~ 1.3 billion positions and results in one thousand times more data than tests that use microarray-based genotyping. This enables imputation (prediction) of unsequenced positions with an accuracy that is sufficiently high for most use cases. Furthermore, unlike DNA microarrays, low-coverage WGS can discover novel genetic variants and it produces more accurate results for individuals that don’t have European ancestry. Table 1 shows a comparison with other commercially available DNA tests. In summary, we believe that the answer to the ‘genotyping vs sequencing’ question is low-coverage Whole Genome Sequencing since it is a better test for the same price.
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Table 1. Comparison of commercially available DNA tests as of May 2019.