Next-generation sequencing has become the most powerful diagnostic tool in medicine. From gene panels to whole genomes — finding answers in the code.
The diagnostic paradigm in genetics has shifted from phenotype-driven single-gene testing to sequence-first approaches that interrogate hundreds or thousands of genes simultaneously. This has compressed the diagnostic timeline from years to weeks and increased diagnostic yields across virtually every clinical indication.
50-500 genes targeted to a clinical indication. Fast, affordable, high depth. Best for well-defined phenotypes (e.g., epilepsy, cardiomyopathy, hearing loss).
~20,000 genes, ~85% of known disease-causing variants. The workhorse of rare disease diagnosis. $250-500 per test.
Complete 3.2 billion base pairs. Captures structural variants, intronic mutations, repeat expansions. Rapidly becoming cost-competitive with exome.
PacBio and Oxford Nanopore. Resolves repeat expansions, structural variants, and methylation patterns that short-read sequencing misses entirely.
The probability of finding a molecular diagnosis varies dramatically by clinical indication and testing strategy. Published diagnostic yields for exome/genome sequencing include:
Trio analysis (proband + both parents) consistently outperforms singleton testing, particularly for identifying de novo variants in neurodevelopmental phenotypes.