We provide different DNA sequencing options to choose from. Our Sequence Analysis uses targeted next generation sequencing (NGS) to detect single-nucleotide variants (SNVs) and small insertions and deletion (INDELs) in the patient's DNA.
Alternatively, targeted Del/Dup (CNV) Analysis uncovers larger changes in the DNA. Both of these analyses can be combined in our Plus Products.
We also provide Whole Genome Del/Dup (CNV) Analysis to screen larger changes throughout the genome. We offer also Whole Exome Sequencing (WES) as an efficient and comprehensive test where all protein-coding genes of the genome are sequenced to provide diagnoses in genetic disorders across various medical specialties.
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 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 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 recognize point mutations, small insertions and deletions, or 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.
The Sequence Analysis Panel is negative.
The 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 the 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. 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.
Sequence Analysis is considered a standard way to analyze next generation sequencing (NGS) data for finding a genetic cause for Mendelian disorders. Standard sequence analysis enables detection of aberrant nucleotide order, most commonly single nucleotide variation (e.g. point mutations) causing either synonymous or non-synonymous change at amino acid level. Non-synonymous changes can be either missense variants (amino acid substitution by another) or nonsense variants (generation of premature stop codons). Standard sequence analysis also detects small insertions, deletions and their combinations, indels, up to 50 base pairs.
Our panels are designed to cover the majority of the genes with established association with a certain disease or disease group, thus offering maximal differential diagnostic power. In general, targeted panels cover protein coding parts of the genes (exons) and related splicing regions, but not intronic regions where alterations are an extremely rare cause of Mendelian disorders. However, Blueprint Genetics Sequence Analysis Panels cover also vast majority of disease causing non-coding variants present in HGMD Professional mutation database.
With targeted sequencing, it is possible to identify all mutations that have been previously linked to specific genetic disorders as well as novel variants in the disease-associated genes.
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