Dr. Andrew Stergachis: ‘We were able to precisely resolve the genetic and molecular basis of (the individual patient’s) condition, thereby providing both her family and care team with answers to help support her moving forward.’
[Editor’s Note: Recently, Nature Genetics published, “Synchronized long-read genome, methylome, epigenome and transcriptome profiling resolve a Mendelian condition.” The corresponding author is BBI’s Andrew Stergachis, M.D., Ph.D. The paper represents a groundbreaking demonstration of using long-read multi-omic sequencing to resolve the genetic and molecular basis of a Mendelian condition.]How are findings in this paper moving researchers toward a greater understanding of genetic variants?
One of the biggest challenges in clinical genomics is that we have a very limited understanding of which genetic variants actually contribute to human disease. Emerging genomic sequencing technologies are well-equipped to accurately identify genetic variants. But the challenge is that each individual has over 4 million genetic variants, with the far majority of these being in genomic regions that we do not understand well. So genomic sequencing alone will result in the identification of 4 million potential variants in each individual that could be contributing to their health.
The premise of the paper is that rather than just measuring whether a genetic variant is present or not, “Can we, at the exact same time, measure whether or not that variant is impacting how a cell is actually functioning?” However, the challenge comes down to: How do we measure all the different diverse functions of the cell in a streamlined manner that gives us an accurate reflection of what’s going on?
