Whole exome sequencing (WES) is a powerful tool that can provide insights into the genetic causes of disease. WES can identify mutations in genes associated with inherited conditions, diagnose rare diseases, and guide treatment decisions. Here we provide an overview of WES, how it is performed, and its potential applications.
Genetic testing has been employed in healthcare areas like cancer and prenatal diagnostics for some time now.
Whole exome sequencing is a popular genetic test choice, and that’s increasingly being used to understand what is causing a condition or a set of symptoms.
Exome sequencing is done at certified laboratories by specialists who extract the DNA from saliva or blood.
The geneticists and bioinformaticians then sequence the exome from the DNA extracted to look for mutations and variation.
What Is The Exome?
The entire DNA content of a human, called the genome, is made up of more than 3 billion base pairs (meaning: the letters A, T, G, and C).
Not all of these 3 billion letters can provide instructions for forming proteins.
Only 1-2% of the entire DNA can form protein. This portion of the DNA, also called the coding region, is known as the exome.
85% of all genetic changes associated with diseases can be found in the exome.
So, in clinical settings, whole-exome sequencing is more commonly done than whole-genome sequencing.
How’s Whole Exome Sequencing Done?
The whole exome sequencing is done in three steps.
Step 1: DNA Isolation and Preparation
There are many techniques to isolate the DNA from the sample, and the method employed depends on the application.
Commonly arrays are used, where probes are designed to capture the portions of interest.
Step 2: DNA Sequencing
DNA sequencing determines the order of the four letters (A, T, G, and C) that make up the DNA molecule.
Sanger sequencing technology is the original one that was a breakthrough in helping scientists determine the human genetic code.
But it was a time-consuming and expensive technology.
Fast forward to a few years later, next-generation sequencing (NGS) took the genetic world by storm with a faster turnaround time and less heavy on the pocket.
With NGS, it is possible to sequence large amounts of DNA, like all the portions that contain the code to produce proteins (exome).
Step 3: Data Analysis
Analysis of the human genome is a data-heavy process.
Decoding as little as 1% of human DNA produces data of around 8 GB.
There are several programs to decode these reads.
Variants (or genetic changes) are present in several file formats like FASTQ, BAM/CRAM, and VCF.
Applications of Whole Exome Sequencing
Rare Variant Mapping
A rare variant is a genetic change that alters gene function and occurs at a low frequency in a population.
Rare variants may play a significant role in complex diseases.
Since most disease-causing variants are found in the exome, exome sequencing remains a very active and ongoing area of research in discovering rare variants.
Discovering Mendelian Disorders
Mendelian disorders are a type of genetic disorder that occurs when an alteration in single genes is inherited from the parents, resulting in disease.
Mendelian disorders are typically very severe.
So the genetic mutation causing the disorder is presumed to be very rare in the population.
Exome sequencing uses advanced technologies that can help discover these variants.
Exome sequencing can help identify the underlying genetic mutation causing a disease.
Having this information can influence the diagnostic approach and treatment options.
Further, it can predict the inheritance pattern of the condition, making it possible to test at-risk family members.
Risks And Benefits Of Exome Sequencing
There are many potential benefits of exome sequencing.
- Can identify variants that increase your risk for a serious condition. For example, if your medical practitioner learns you are at an increased risk for heart disease, they may suggest suitable preventive approaches.
- Prenatal detection of genetic conditions. Exome sequencing can be done for a fetus giving ample room to make informed decisions. This is especially useful for certain conditions where early treatment can make a world of difference.
- Cost-effective. Compared to whole genome sequencing, whole exome sequencing doesn’t burn a hole in your pocket.
There are many psychological repercussions to getting your genome sequenced.
Since exome sequencing can reveal most disease-causing variants, you may uncover that you are at risk for a condition you weren’t originally planning to investigate.
Since you share your DNA with other family members, this type of finding can have an impact on them as well.
Talking to your healthcare provider about all the risks involved before electing for whole exome sequencing is important.
Summary: Whole Exome Sequencing
- Whole exome sequencing (WES) analyzes the protein-coding part of the DNA (about 1-2%) to reveal disease-causing (or risk-increasing) genetic variants.
- WES is done using saliva or a blood sample, and the DNA is sequenced with next-generation sequencing technology.
- WES is used in research settings for identifying rare variants and discovering Mendelian disorders.
- In clinical settings, WES is a popular choice to diagnose and identify the cause of a disease. This impacts the treatment options and screening for other family members.
- Before taking the test, it is important to understand and discuss the potential benefits and risks of WES with a qualified medical practitioner.