Exome

The exome is composed of all of the

The human exome consists of roughly 233,785 exons, about 80% of which are less than 200 base pairs in length, constituting a total of about 1.1% of the total genome, or about 30 megabases of DNA.^[2][3][4] Though composing a very small fraction of the genome, mutations in the exome are thought to harbor 85% of mutations that have a large effect on disease.^[5]

Definition

It is important to note that the exome is distinct from the transcriptome, which is all of the transcribed RNA within a cell type. While the exome is constant from cell-type to cell-type, the transcriptome changes based on the structure and function of the cells. As a result, the entirety of the exome is not translated into protein in every cell. Different cell types only transcribe portions of the exome, and only the coding regions of the exons are eventually translated into proteins.

Next-generation sequencing

With either form of sequencing, whole-exome sequencing or whole genome sequencing, some have argued that such practices should be done under the consideration of medical ethics. While physicians strive to preserve patient autonomy, sequencing deliberately asks laboratories to look at genetic variants that may be completely unrelated to the patient's condition at hand and have the potential of revealing findings that were not intentionally sought. In addition, such testing have been suggested to have imply forms of discrimination against particular groups for having certain genes, creating the potential for stigmas or negative attitudes towards that group as a result.^[12]

Diseases and diagnoses

Rare mutations that affect the function of essential proteins constitute the majority of

For example, Bartter Syndrome, also known as salt-wasting nephropathy, is a hereditary disease of the kidney characterized by hypotension (low blood pressure), hypokalemia (low potassium), and alkalosis (high blood pH) leading to muscle fatigue and varying levels of fatality.^[14] It is an example of a rare disease, affecting fewer than one per million people, whose patients have been positively impacted by whole-exome sequencing. Thanks to this method, patients who formerly did not exhibit the classical mutations associated with Bartter Syndrome were formally diagnosed with it after the discovery that the disease has mutations outside of the loci of interest.^[5] They were thus able to gain more targeted and productive treatment for the disease.

Much of the focus of exome sequencing in the context of disease diagnosis has been on protein coding "loss of function" alleles. Research has shown, however, that future advances that allow the study of non-coding regions, within and without the exome, may lead to additional abilities in the diagnoses of rare Mendelian disorders.

• Coding strand
• Exome sequencing
• Gene structure
• Non-coding DNA
• Non-coding RNA
• Transcriptome
• Transcriptomics

References