White papers
The genetic horizon – Improving clinical sensitivity in difficult-to-sequence genes for rare hereditary disorders
Oct 17, 2018

From bench to bedside: The genetic horizon

The long-awaited promise of tailored treatments for individual patients based on their genetic makeup is beginning to materialize. Next-generation sequencing, along with artificial intelligence, have facilitated the rapid, accurate analysis and interpretation of genomic data for disease-causing variants which may be treatable through emerging gene therapy technology.

The number of clinical trials and drug development pipelines for rare disease are quickly growing and, encouragingly, the first approved treatments have been successful.

At Blueprint Genetics, we feel that being fully transparent about our successes, challenges, and limitations is key to making effective, powerful diagnostic tools available to the rare disease community. By sharing our own troubleshooting strategies, we hope to move genetic diagnostics and the promise of precision medicine forward.

In this white paper:

  • Our approach to difficult-to-sequence genes — Opening the black box
  • A clinician–lab partnership — Providing sufficient clinical information
  • Difficult-to-sequence genes at a glance – Key examples
  • Case reports from RPGRSMN1/SMN2, and PKD1
  • On the R&D horizon – Upcoming targets

The importance of transparency in clinical genetic testing

Our ability to accurately detect disease-causing variants in the human genome is continuously improving. Single nucleotide variants, small insertions and deletions, and exon-level deletions and duplications can be reproducibly detected, almost throughout the entire genome, and their identification is becoming more important in clinical care. Absolute transparency in genetic diagnostics is essential so that clinicians understand the quality and limitations of any given test and the suitability of the test for their patient. Blueprint Genetics is committed to providing full disclosure of our analytic validation of testing, the description of our technologies and datasets used in the diagnostic process, and to the critical assessment of the performance metrics.

Actionability for the rare

Rare diseases comprise a heterogeneous group of thousands of genetically and clinically distinct disorders. Molecular diagnosis of these disorders has the potential to allow a patient’s treatment to be tailored and optimized. Recent advances in gene therapy hold tremendous promise as a cure for these devastating diseases. As an example, retinal gene therapy has demonstrated the potential to cure different forms of inherited vision loss (www.luxturna.com). Similarly, targeted treatments for Spinal Muscular Atrophy (SMA) have recently entered clinical trials (www.avexis.com). The power of gene therapies is in the specificity of the treatments: understanding the genetic mechanism of the disease and creating a therapy to counter it. Genetic testing therefore becomes an integral part of rare disease management as determining the precise gene and variant responsible for the disease is a prerequisite for targeted treatments and gene therapy.

Ongoing challenges

Clinically relevant but highly homologous and repetitive regions within important genes are an ongoing challenge to analyze. Blueprint Genetics remains committed to resolving difficult-to-sequence regions that are hard to validate, interpret, and confirm by developing custom solutions. In this white paper, we share our strategies and what is next in our R&D pipeline.


Samuel Myllykangas
COO, PhD, Founder Blueprint Genetics

Read the entire white paper here.

Last modified: October 29, 2020