The exome represents the entirety of all known coding exons of the genome. Although exons only comprise 1%–2% of the human genome, 89% of all known disease-causing mutations are estimated in these regions. Therefore, it is often reasonable to perform a targeted, conventional exome analysis. The aim of whole exome sequencing is the identification of genetic variants in a specific sample. A variation in the protein-coding region can, for example, cause diseases such as multiple endocrine neoplasia type 2B, Huntington’s disease, or Creutzfeldt-Jakob disease. Such disease-causing variants can be identified using whole exome sequencing approaches.
However, especially for complex disease patterns, disease-relevant variants might also be located in non-coding regions. These regions are usually not covered by conventional whole exome sequencing approaches. With our ExomeXtra® Sequencing products, disease-relevant variants in non-coding, intronic, or regulatory regions are covered. We use dedicated databases, such as the Human Gene Mutation Database (HGMD) or the ClinVar database, as resources for these disease-relevant variants. We include variants that are classified as pathogenic or likely pathogenic in our enrichment. As the evaluation and classification of variants can change, we regularly update our ExomeXtra® products based on the latest scientific knowledge. Thus, not only are newly classified pathogenic or likely pathogenic variants included in the enrichment, but variants that are no longer classified accordingly are removed.
Our ExomeXtra® does not only include interesting variants in non-coding regions; with the new and unique CNV backbone, genome-wide analyses and high-resolution detection of copy number variations (CNVs) are possible – without sequencing the whole genome! For the CNV backbone, genomic information is fetched in regular intervals from the DNA. With the CNV backbone, deletions and duplications in the entire genome can be detected, increasing the probability of finding disease-causing mutations. The CNV detection in both coding and non-coding regions is unique in exome sequencing.
As more data is generated and analyzed with the ExomeXtra® compared to conventional exome sequencing approaches, a higher sequencing output is required to adequately evaluate the sequencing results and identify the complex genetic cause of a disease.
Figure 1 | ExomeXtra® Sequencing vs. Whole Exome Sequencing. In Whole Exome Sequencing (WES), exonic regions (E) are sequenced with a sufficient sequencing depth to confidentially call variants. ExomeXtra® Sequencing uses a CNV backbone for genome-wide CNV calling. All disease-relevant variants in coding and non-coding, intronic (I) regions are enriched to confidentially identify the genetic cause of a disease.