Whole-genome sequencing is increasingly inexpensive and accessible, making it a tempting tool for many labs and researchers interested in gene sequences. However, a whole genome is enormous and much of it has limited, no or unknown biological significance, resulting in a mountain of data that researchers must then sift for their desired answers. Many modern genomics tools aim to achieve a compromise between the vast breadth of a whole-genome sequence and the much finer results that come from targeted gene panels. The Applied Biosystems CytoScan XON Suite is one such tool.
Our poster “Exon-Level Detection of Human Copy Number Variation Using High-Density DNA Oligonucleotide Arrays” discusses the properties of the Cytoscan XON Suite. Containing arrays, reagents and software, the Cytoscan XON Suite covers the whole exome. To deliver both this fine resolution and wide coverage, the CytoScan XON Suite offers a tiered organization scheme based on the ClinVar classification in its output, organizing results into broader and narrower categories based on clinical relevance. This four-level output format helps researchers use the full range of CytoScan XON’s flexibility as their needs vary, from the first tier’s 7,003 genes of known high clinical relevance to its complete set of 25,980. Its 6.85 million empirically selected probes are particularly well suited to detecting and sequencing copy-number variations (CNVs), which are implicated in a variety of genetic conditions and which can be difficult to detect with other sequencing tools. The CytoScan XON Suite’s exon-level CNV array has such thorough coverage that it can detect CNVs of less than three exons, small enough that many other arrays and whole-exome sequencing tools fail to recognize them.
The efficacy of the Applied Biosystems CytoScan XON Suite is perhaps best demonstrated in the case of Stevenson et al.’s study of a family with Waardenburg syndrome.1 Both parents had Waardenburg syndrome, a chromosomal abnormality that results in a distinctive appearance and sometimes hearing loss and other challenges. Initial genetic tests on the parents suggested that their child, while virtually certain to also have Waardenburg syndrome, should otherwise be healthy. Instead, the family endured the stillbirth of a child far more severely affected than either of them, which other genetic tests neither predicted nor explained after the fact. Using the CytoScan XON Array, the researchers determined that the parents’ genotypes varied just enough from one another to impose a compounded, lethal genetic legacy on their child via copy-number variants that the previous genetic assays had missed. Scenarios like these, in which parents with different heterozygous chromosomal abnormalities can produce offspring homozygous for specific deletions or mutations, who are then severely or lethally affected, can occur across a variety of genetic conditions and are difficult for other methods to predict. This necessitates new, more sensitive tools like the Applied Biosystems CytoScan XON Suite.
As discussed in our poster “Characterization of Exon-Level Genomic Copy Number Changes in 1,855 Normal Individuals,” the Applied Biosystems CytoScan XON Suite has also helped refine our understanding of genome-wide patterns based on regional heritage. Medicine is slowly recognizing that members of different ethnic groups show shared patterns that can distinguish them from other ethnic groups and that these patterns can affect susceptibility to disease. As medicine becomes more and more personal, understanding these patterns is necessary for public health, enabling medical professionals to address their patients’ needs in a more informed and aware way. Using the high sensitivity of the CytoScan XON Suite and existing human genome libraries, researchers were able to show that copy number variations in the exome are not a substantial part of the differences between ethnic groups. This raises questions for additional research and helps suggest which avenues of inquiry might be more fruitful to pursue in the ongoing quest for truly personalized medicine.
For more information about the possibilities that the Applied Biosystems CytoScan XON Suite offers, please enjoy these posters discussing the capabilities and uses of the Cytoscan XON Suite in detail.
1. Stevenson, R. E., Vincent, V., Spellicy, C. J., Friez, M. J. & Chaubey, A. (2018). “Biallelic deletions of the Waardenburg II syndrome gene, SOX10, cause a recognizable arthrogryposis syndrome,” Am. J. Med. Genet. A. 176: 1,968–1,971.