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.
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.