Full exome sequencing
Whole Exome Sequencing (WES) is a molecular genetic diagnostic method that enables the simultaneous analysis of a large number of coding DNA sequences. During the analysis, the exonic regions of genes that contain information required for protein synthesis are assessed. The test is not limited to a predefined list of diseases or genes and involves analysis of the exome as a whole. Therefore, the resulting data may include variants in genes with a well-established role in disease development, as well as variants in genes whose clinical significance remains insufficiently determined.
The method can detect various classes of genetic changes, including:
- single-nucleotide substitutions, as well as changes involving several nucleotides (SNVs and MNVs);
- small structural changes in the DNA sequence in the form of insertions or deletions of fragments (indels) up to 50 base pairs in length;
- changes in the dosage of genetic material belonging to the CNV category, including losses or additional copies of gene regions of various sizes.
- The ability to detect such changes depends on the characteristics of the methodology used and is subject to certain technical limitations.
When WES is recommended:
The test may be used in diagnostically challenging cases when standard examinations and previously performed genetic tests have failed to determine the cause of the disease, but the overall clinical presentation continues to suggest a hereditary origin of the condition.
The most informative approach is often a family-based analysis, in which samples from the patient and both parents are analyzed simultaneously.
Comparison of the results makes it possible to determine whether an identified variant is inherited or has arisen de novo, as well as to assess its pattern of inheritance within the family.
During the analysis, changes may be identified in genes for which, at the time of testing, there is insufficient evidence to determine their clinical significance unambiguously. Such findings require careful interpretation and cannot be regarded as a confirmed cause of the disease solely on the basis of their detection.
The significance of WES results may change as genetic research advances. The emergence of new scientific publications, expansion of databases, and revisions to the classification of genes and variants create opportunities for the re-interpretation of previously obtained results.
Therefore, in certain clinical situations, whole exome sequencing data can be used for re-analysis in light of current information that was not available at the time of the initial testing.