About DNA structure
To understand the meaning of exome sequencing, a few words must be said about the basic structure of our DNA.
DNA is a giant molecule that consists of more than 3 billion base-units, called nucleotides. There are four types of nucleotides, these are responsible for coding all the information necessary for creating proteins necessary for our body’s function.
These basic building blocks of our DNA are cloned and translated into biologically active proteins. Changes in the genome are reflected in changes in the DNA sequence – that in turn create different proteins.
Each DNA sequence coded to a protein is called a gene. The estimated number of genes in the human DNA is around 20,000. This is a relatively low amount in relation to numbers assumed in the past.
Apparently, a large part of the genetic material is not directly coded to create proteins. A large percentage of DNA is responsible for regulating the proteins (the time and amount of protein production according to the DNA pattern). A large percentage seems to have no specific role.
Some of this “excess” DNA is a biological remnant of viruses that found their way into the genome, clones of different fragments and genes, and vast areas whose purpose is not entirely clear. Aside of those, even genes themselves contain areas that are unnecessary to the final creation of protein.
Each gene comprises coded and non-coded areas, called exons and introns. The role of the introns is not entirely clear, although changes in these portions do not reflect in the protein structure. Likewise, changes in other non-coded portions of the gene are sometimes without biological outcome, although this is not always the case.
Genome sequencing in genetic screening
One of the most thorough and effective methods of genetic screening is full genome sequencing. This method is based on a full analysis of a patient’s entire genetic material, which is listed according to its base pillars in the cells.
The analysis results are compared to known genome databases to detect changes that can be related to genetic diseases.
Full genome sequencing uses a simple sample of cells. Genetic material can be found in almost all of our body cells and is identical in them all. In most cases, the test uses a blood test in which the white blood cells have been isolated (since red blood cells do not contain DNA).
How can sequencing become more accessible?
Full genome sequencing is clearly a powerful tool for identifying diseases. However, this method is currently expensive and is not accessible to everyone.
Up until a decade ago, great effort was put into mapping the entire human genome. This project required international co-operations and great resources. Technological developments in recent years have allowed genome mapping to become more accessible, faster, and cheaper.
Still, whole genome sequencing still requires great costs and lab resources which prevents it from becoming an accessible and routine test.
Is there a way to use extensive mapping techniques in a more efficient and accessible way?
What is exome sequencing?
Exome sequencing is a method created to solve this problem. In this method, only the coded parts of the DNA are sequenced and the non-coded parts that do not belong to known genes are left out.
Since most genetic change and mutations are in the coded portions, this technique maps a much smaller percentage of genetic material with minimal loss of important mutations.
Exome sequencing can detect most known genetic hereditary diseases. It can also identify unknown mutations to try and understand them. The test’s main disadvantage is its inability to detect changes in the regulatory portions of the DNA and in the areas whose role is yet unclear in protein coding.
For these reasons, exome sequencing allows a full testing of the human genome, at a more reasonable price.
What diseases can the test detect?
Exome sequencing can help detect many complex diseases. Some of those diseases, such as heart muscle diseases (cardiomyopathy) are known to be related to certain genes, some of which have not yet been fully identified. This test enables a quick understanding of the affected gene, which allows the patient and their family to choose to undergo further tests.
Exome sequencing is suitable to any patient with a disease whose background is unclear. It can also help those with unclear diagnosis, or a suspicion for a genetic disease where the coded gene responsible for it has yet to be identified. In addition, patients with a polygenic disease can undergo the test.
Modern sequencing uses advanced technology that can identify the basic structure after the division of the genome into portions. Since this is a whole sequencing, the results need to be interpreted. Often, unclear changes are detected, and it may be unclear whether these changes are connected to the patient’s condition or if they may affect their children in the future.