An Overview of Whole Exome Sequencing (WES)

In This Article

Whole exome sequencing (WES) is a molecular genetic process that can be used to identify alternations in genes. This method is relatively new, and as the technology advances rapidly, further research and the discovery of more practical clinical purposes are expected to emerge.

Genetic testing is becoming very popular—you can purchase products that use your hair or saliva samples to pinpoint certain genetic traits and to learn which ethnic backgrounds are part of your ancestry.

WES is a bit different from this type of genetic testing because it is used to identify abnormalities in all of your genes, even if these abnormalities have not been previously associated with any disease. For example, it is not the right test to look for a specific gene abnormality, like the genes identified in relation to breast cancer.

How Genes Work

WES can be used to look for patterns to find the genetic cause of a medical disease. Your chromosomes are molecules that contain your genetic code. (You have 23 pairs of chromosomes—these are also called DNA molecules.) They are composed of long strands of nucleotide molecules. Your body reads the sequence of the nucleotides on your chromosomes to produce proteins. 

Alterations of the nucleotide sequence in DNA molecules account for the variations in traits among all of us.

Alterations that cause disease are often referred to as mutations.

It helps to understand some basics about genetics if you are thinking about using WES.

Genes and Genomes

All of your body’s traits are formed through protein production. Genes are nucleotide sequences that code for the proteins that end up producing your traits. All of the genetic coding of all of your 46 chromosomes is referred to as your genome. 

Exons

The nucleotide sections of a DNA molecule that code for genes are called exons. They are interspersed with introns, which are nucleotide sequences that do not code for traits. A single gene may be composed of several exons that code for multiple proteins. Exons account for only 1 to 2 percent of your total DNA.

Each exon actually begins with a nucleotide sequence that prompts protein production to start, and ends with a nucleotide sequence that prompts the termination of protein production.

Exome

All of the exons in your whole entire set of chromosomes are referred to as the exome. Whole exome genome sequencing looks at your whole exome to identify abnormalities that could be responsible for a disease or a health problem.

Limitations 

WES is quite extensive, and it examines all of the genes in your body. However, it does not examine introns at all. It is believed that introns may have some effect on your body, although that effect is not fully understood and is not currently thought to be as influential as the influence of exons.

Process

WES uses a blood sample to analyze your genomes. Every cell in your body contains a full copy of all 46 of your chromosomes, so blood cells are adequate for this type of test. 

WES testing uses a molecular technique called hybridization, which compares the nucleotide sequence of the sampled DNA with a standard or “normal” DNA sequence. 

WES can pick up on mutations that are already known to cause disease, and it can also detect alterations in the genetic code that have not already been associated with a disease.

Where to Get Tested

There are many laboratories that run whole exome sequencing. If your doctor wants you to have whole exome sequencing, you might have your blood drawn at your doctor’s office and the sample can be sent to a specialized lab for interpretation.

If you are getting the test without a doctor’s order, you can contact a specialized lab that does WES testing directly and ask them for their instructions.

Cost

It is important that you check the cost of testing, and also check whether your health insurance will cover the cost of the test. WES is a relatively new type of technology and your insurance company may or may not cover the cost, depending on their policies.

If you are planning on paying for the test yourself, the cost can range between $400 and $1,500.

Considerations

If you or your child is going to have a whole genomic sequencing, you need to be aware of the implications. There are a variety of things to consider before undergoing WES.

Privacy

Your genetic results can become a part of your medical record, especially if a doctor orders your test and if your health insurance is paying for it. Your health insurance company, the company that runs the test, and potentially any of their vendors (or anyone who hacks into their computer systems) could learn whether you carry the genes for any known genetic trait.

Given that these are genetic tests, there are implications that could affect people who are related to you as well. While there are laws to protect your privacy and regulations that prevent pre-existing conditions from affecting your health coverage, this level of information is unprecedented. There may be unanticipated personal and professional outcomes in terms of privacy.

Awareness of Disease Susceptibility

Many have the concern that genomic testing will reveal more about their health than they initially bargained for. Except in extremely rare cases—such as Huntington's disease—genetic testing does not reveal a person's medical future.

It has the potential to reveal, in the majority of cases, that a person has an increased risk for various medical disorders. Since a person is so thoroughly tested, there may be a few abnormalities that are discovered. However, many will never lead to a specific disease or condition.

At this phase of discovery, it is likely that no one would even be able to discern what the exact medical implications are for a person's future, or which "abnormalities" will lead to a certain disease or condition, for instance.

Deciding on a Test

There are several similar genetic tests that evaluate your chromosomes differently than WES, and there are advantages and disadvantages to each different type of tests.

Chromosomal Analysis

Chromosomal analysis is also described karyotyping. This test can analyze all of your chromosomes to see if there are changes, such as an extra copy of a chromosome or a missing chromosome.

Chromosomal testing can also detect substantial changes in chromosome structure, such as elongated or short chromosomes.

Karyotyping can identify conditions such as Down syndrome, in which there is an extra copy of chromosome 21. It cannot, however, detect small mutations in a gene.

Whole Genomic Sequence

A whole genomic sequence is similar to whole exome sequencing except that it is more extensive. It looks at the whole entire genome, including the intron sequences. Whole genomic sequencing is more costly than whole exome sequencing as well.

Molecular Genetic Tests

Also described as microarray genetic testing, these studies compare a small section of your DNA to known genes or to a selected DNA sequence to find alterations or known mutations in a specific area on a chromosome.

These tests are useful if you have symptoms of a condition caused by a mutation in a known location of a chromosome, such as the genes for Huntington's disease and some breast cancer genes. 

A Word From Verywell

WES is still a relatively new method of genetic testing and it isn't yet completely clear how it can be best applied in practical use.

There are serious issues to consider if you or a loved one is having a genetic test. If the treatment of a suspected genetic condition is tailored to the genetic defect, you potentially have a lot to gain through the test. Even if the test will not affect your treatment, the results may be beneficial in understanding your prognosis and letting family members know they may be at risk. Be sure to carefully think of how you will react to normal or abnormal results and to carefully consider your privacy before having the test.

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