Impact of Genomics on Insurers – Part 2
The Different Strains of Genetic Testing
Curious to learn about your prehistorical ancestor from a drop of saliva? Or find out which combination of genetic variations leads to hereditary heart defects? Both scenarios are now possible thanks to genetic testing. Behind the umbrella term «genetic testing» are a surprising number of different techniques and procedures, which in turn produce very different data. In the second article of our series highlighting the growing field of genomics, we delineate various types of genetic tests.
In our previous article, we described how genetic testing is becoming a household term. This is partly due to the rise of direct-to-consumer testing companies, which offer genetic screening at very affordable rates. Most of these companies are accessible worldwide and are built with a strong online presence. However, it must be noted that while the data collected by these services do provide some information to customers, the in-depth insight is still far less comprehensive than the data that genetic tests produce within clinical research and academia.
In the following, we provide an overview of the different testing methodspresently available , as well as their current and potential use within the healthcare sector.
Single-Gene Testing and Gene Panels
Single gene testing requires less time and resources than other testing. As the name implies, only a specific gene or a part of a gene is sequenced (see fig. 1A). This technique is useful when a researcher is looking for a specific mutation in a specific gene. A well-known application of single-gene testing is its use to detect breast cancer inducing mutations in the BRCA1 gene. This gene gained worldwide attention when a well-known actress published her results. Likewise, most inherited mono-genetic disorders can be detected with this technique, but many interactions between genetic sequences that are not near to each other may still signal diseases and other important observations, but remain hardly detectable with this method.
An extension of the targeted single-gene technique consists in sequencing a panel of genes simultaneously (between 2 and 200, see Fig. 1B). Gene-panels are mostly used for primary as well as confirmatory diagnostics which allow the diagnoses of genetic illnesses or risk dispositions caused by variations in multiple genes.
Single-nucleotide polymorphisms (SNPs, pronounced as «snipps», see fig. 1C) are used to determine more general traits, such as lineage. A large number of very short sequences (between 10’000 and a million) which are tied specifically to known genetic variations in the human population are sequenced simultaneously. This type of test, called SNP genotyping, can be used to confirm paternity or, by extension, ancestry. This is typically the service provided by online direct-to-consumer (DTC) testing companies. While the results of these DTC services can be used to confirm diagnoses, or give general insights on the subject’s hereditary background, they are generally not used to perform genetic diagnosis or in-depth clinical studies.
Sequencing Large Amounts of Genomic Information
All the methods described above cover only very small parts of the human genetic material. To obtain a more exhaustive picture of an individual human’s genome, one must resort to considerably more complicated and expensive procedures that sequence large amounts of genomic DNA without limit to specific targets (see fig. 1D-E).
These approaches are not yet fully automated or standardized, but are generating a very large amount of data. Consequently, significant computational power and scientific expertise is needed to process the sequence information. Analysis can take several months or even years for initial questions to be answered. Therefore, there are limited examples of clinical studies based on these approaches available today. However, this type of data is extremely useful when one tries to identify new genetic causes for a disease. Some cases of diagnoses can be established from this data like determining the hereditary causes of rare cardiac problems.
As fig. 2 illustrates, the cost for sequencing large amounts of genomic information has decreased tenfold over the last couple of years, due in part to technical advancements collectively called «next generation sequencing» (NGS). We can expect that progress will further continue making genome sequencing both cheaper and easier to perform.
Two approaches for obtaining large scale genomic information of an individual are described hereafter.
Whole Exome Sequencing (WES)
Whole exome sequencing refers to sequencing only DNA coding for proteins, which comprises about 1% of the total human genome (see fig. 1D), taking less time and effort to analyze than the whole genome. This reduces costs significantly compared to whole-genome sequencing and allows insights into causes of many diseases as well as other observable traits. However, non-coding regions of the DNA that are not expressed into proteins still influence many diseases, a connection that is missed with this approach.
Whole Genome Sequencing (WGS)
In the case of whole genome sequencing, the genome of an individual is sequenced in its entirety (see fig. 1E). Therefore, it also captures variations and mutations in non-coding regions of the genome, many of which very much still impacting our phenotype.
With equipment required for WGS becoming faster and cheaper over the last couple of years, the number of sequenced human genomes has been growing exponentially (see fig. 3). Hence, an age in which everybody in a developed country will have their full genome sequenced is coming closer.
In summary, genetic testing results are diverse and can give very different types of information. Thus they are used in different circumstances and with different purposes. Our next article will take a closer look at the use of genetic information in the clinical field.