Targeted Del/Dup (CNV)

In clinical genetic diagnostics, Deletion/Duplication (CNV) Analysis is used to detect disease-causing deletions or duplications from the genome. The size of the alteration may vary from single exon (<150-1000 bps) to multiple genes, up to chromosome level changes visible by light microscopy. Deletions and duplications with a size larger than 1,000 bases (>1 kb) are called copy-number variations (CNVs). NGS and capillary sequencing have known limitations to detect CNVs, thus alternative methods such as CGH arrays and MLPA have been traditionally used for CNV detection. However, CGH arrays are insensitive for detecting CNVs smaller than 50 kilobases and MLPA covers usually only small number of genes in the assay.

Blueprint Genetics provides a high-resolution Del/Dup assay to overcome these diagnostic limitations. Blueprint Genetics Del/Dup Analysis Panels utilize the OS-seq based high-coverage NGS data to detect Del/Dups. The assay has a detection limit for Del/Dups at single to six exon level in the same genes that are covered by sequencing panels. The resolution varies throughout the genome based on depending on exon size, sequencing coverage and sequence content. Del/Dup analysis is offered both as an independent product and in combination with Sequence Analysis Panels.

Del/Dup analysis is considered an adequate first line test for disorders where frequency of disease-causing deletions/duplications is high. Furthermore, testing for deletions and duplications is found useful in autosomal recessive conditions when only one variant is identified by sequence analysis. It should be noted that Del/Dup analysis does not recognise point mutations or small insertions and deletions, nor sequence repeats or disorders caused by mutations in mitochondrial DNA.

When to choose Del/Dup (CNV) Analysis:

  • The patient is suspected to have a genetic disorder mainly caused by deletions and duplications
  • Sequence Analysis Panel is negative.
  • Sequence Analysis Panel identifies only a single variant for an autosomal recessive disorder.
  • For male patients with X-linked disorders where no mutation has been identified by Sequence Analysis Panel.
  • For female patients with X-linked disorders with one or no mutations identified by Sequence Analysis Panel.

Plus Analysis – a combination of Sequence Analysis and Del/Dup (CNV) Analysis

The underlying genetic defect for a majority of the disorders may be either detectable by Sequence Analysis or by Del/Dup Analysis. In these cases, the Sequence Analysis and Del/Dup Analysis together, so called Plus Panels, provide the highest diagnostic yield. Blueprint Genetics Plus Panel prevents unnecessary clinical appointments after negative first line test results which are more common if only sequencing or Del/Dup analysis is performed at a time. Thus, it has potential to shorten the time for diagnostic process and to reduce total expenses compared to cascade screening. Many genetic changes can only be detected by Del/Dup analysis, and would be missed by classic Sequence Analysis alone. Importantly, multiple mutations in the same gene may cause more severe disease for the affected person and therefore, determination of all the potential genetic causes for the phenotype is essential to fully understand the contribution of genetics to the patient’s disease.

Targeted Del/Dup (CNV) analysis is used to detect bigger disease causing deletions or duplications from the disease-associated genes.