whole exome sequencing

There have been great advances in genetic technology over the past few decades. These advances began with identifying chromosomes, the packages that contain all of our genetic instructions that are inside every cell of our bodies, to now identifying and reading through our DNA, the smallest structure of our genetics inside those chromosomes. Having the ability to read through the coding of our DNA in every chromosome has led us to identify so many specific genetic causes of diseases and conditions and has even led us to better treatment options. One new tool that is now available because of these advances is whole exome sequencing.


The Human Genome Project

All of our DNA coding in our bodies, or all the genetic instructions that make up our bodies, is called the human genome. Beginning on October 1, 1990, the human genome was first completely analyzed by the Human Genome Project in 2003. Through a technology called sequencing, the human genome project was able to read through the DNA coding of a human. In doing so they discovered that there are approximately 20,000 genes, or segments of DNA that provide instructions for our bodies. It is important to note that this project did not just sequence the DNA coding of only one human genome, but rather multiple human genomes. 

As genetic testing has advanced, and research has continued to identify genes that cause certain diseases, our ability and ease to perform genetic testing on more and more people has improved. However, there are still many circumstances when genetic testing is performed on someone who has a condition and no cause is identified. Often health care providers will start with basic genetic testing, such as a karyotype or microarray, which analyzes the chromosomes of an individual, and then will proceed to a genetic testing panel. A genetic testing panel is more than one gene (and can range up to 500+ genes) that are associated with a particular health condition that the health care provider thinks is causing the symptoms in an individual. If a genetic testing panel is negative, or no genetic cause is identified to explain an individual’s symptoms, then more and more often health care providers are considering whole exome sequencing. Likewise, if healthcare providers are not completely sure what is causing the health problems in an individual, or if the diagnosis could be many different conditions, then whole exome sequencing can be considered. 


Whole Exome Sequencing (WES)

As discussed earlier, a gene is a segment of our DNA coding that provides instructions, or proteins, for our bodies. Our genes are made up of two different parts of DNA, exons and introns. Exons are the DNA coding portion of the gene that provides the instructions to make proteins for our bodies. Introns are typically interspersed with exons throughout the gene and do not provide coding or instructions for proteins. However, introns are important for our bodies as they help with regulation of our genes, or when our genes are used to make those proteins. Whole exome sequencing (WES) is when all of the exons, or protein-coding regions of our genes, are analyzed and searched for mistakes or mutations that could cause disease. 

Several studies have shown that WES can identify a disease-causing mutation or change in an individual’s genes in approximately 25-30% of cases, and more if there is a family history of the disease. On the other hand, that also means that up to 70% of individuals do not find a genetic cause to their health problems after pursuing WES. While we are capable of performing WES, we still don’t always understand all connections between our genes and disease and may not be able to identify a specific cause to a disease at this time. 

When considering WES, there are a number of points to consider. An individual may find out something about their genetics that has nothing to do with their specific health problem that led them to pursue WES in the first place. For example, some people may discover that they have a change in a gene that can increase their risk of cancer, or another disease. In addition, while WES results can indicate a positive result (a change in a gene was found that causes disease) or negative result (no change in your genes was found), it can also indicate a result called variants of unknown significance. These changes in our genes called variants of unknown significance means that we found a change but do not know enough about that change to classify it as positive or negative. Those types of results are typically re-analyzed over the years and can be reclassified when enough data is gathered. 

Another difficulty of WES is insurance coverage. While many labs are making WES an affordable test, it can still be expensive for many individuals, especially if insurance does not cover the cost. It is important to look into if your insurance covers the cost of WES, and if they do not, discuss with the genetic testing lab that is planning on performing your WES to determine if they can offer an affordable price. 


Genetic Counseling & Whole Exome Sequencing

If you are interested in WES or have a family history of a disease that has not been identified previously, or have exhausted all other genetic testing options, please contact AT-GC to meet with a genetic counselor to learn more about WES. 


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