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Whole Exome and Whole Genome Sequencing: Why are they Regarded as Valuable Methods?

Life Sciences Review | Wednesday, October 20, 2021
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Researchers have discovered that DNA variations outside of exons can affect gene activity and protein production, resulting in genetic disorders—variations that whole-exome sequencing would miss.


FREMONT, CA: DNA sequencing, or determining the order of DNA building blocks (nucleotides) in an individual's genetic code, has accelerated the study of genetics and is one method used to test for genetic disorders. To identify genetic variations, two methods, whole-exome sequencing, and whole-genome sequencing are increasingly utilized in healthcare and research; both focus on new technologies that enable rapid sequencing of large amounts of DNA. These methods are regarded as next-generation sequencing (or next-gen sequencing).


Sanger sequencing (named after the scientist who invented it, Frederick Sanger) was a breakthrough that aided scientists in determining the human genetic code, but it is time-consuming and pricey. The Sanger method has been automated to make it faster, and it is still adopted in laboratories today to sequence short pieces of DNA, but sequencing all of a person's DNA (known as the person's genome) would take years. Next-generation sequencing has sped up the process (sequencing a human genome now takes days to weeks) while lowering the cost.


It is now possible to sequence large amounts of DNA using next-generation sequencing, such as all of an individual's DNA that contains instructions for making proteins. These pieces, known as exons, are thought to account for one percent of a person's genome. 


The exome is the compilation of all the exons in a genome, and the method of sequencing them is known as whole-exome sequencing. This technique identifies variations in the protein-coding region of any gene, rather than just a few genes. Since most known disease-causing mutations occur in exons, whole-exome sequencing is thought to be an efficient method for identifying potential disease-causing mutations.


Researchers have discovered that DNA variations outside of exons can affect gene activity and protein production, resulting in genetic disorders—variations that whole-exome sequencing would miss. Another method, known as whole genome sequencing, dictates the order of all nucleotides in a person's DNA and can detect variations in any part of the genome.


While whole-exome and whole-genome sequencing can identify many more genetic changes than select gene sequencing, the relevance of much of this information is unknown. As not all genetic changes impact health, determining whether identified variants are implicated in the condition of interest is difficult. An identified variant may be linked to a distinct genetic disorder that has yet to be identified (these are called incidental or secondary findings).


Whole exome and whole genome sequencing are valuable methods for researchers and are being used in the clinic. Exome and genome sequencing can help ascertain whether new genetic variations are associated with health conditions, which will assist in disease diagnosis in the future.


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