Next-generation sequencing is a laboratory approach that reads the actual letters of a person’s genetic code, the DNA that carries the instructions for how the body is built and runs. Older sequencing methods could realistically read one gene, or a handful of genes, at a time, which meant a doctor had to guess correctly which single gene to test before an answer could be found. Next-generation sequencing changes this by processing millions of small fragments of DNA all at once, in parallel, rather than one after another. This parallel approach is what gives the technology its name, and it is also what makes it possible to read many genes, or even someone’s entire genetic code, in a single test, at a fraction of the time and cost that reading genes one by one would take.

In practice, next-generation sequencing is offered in a few different forms, and a doctor chooses among them based on the clinical question being asked. A gene panel reads a defined group of genes already known to cause a particular condition or group of related conditions. Whole exome sequencing reads the protein-coding portions of essentially all genes, which make up a small fraction of the total genetic code but contain the great majority of changes currently known to cause disease. Whole genome sequencing goes further still, reading almost the entire genetic code, including the vast stretches between genes that help control how genes are switched on and off.

A doctor recommends one of these tests when a person’s symptoms, or a family’s history, suggest an underlying genetic cause that has not yet been pinned down, and when the range of genes that could plausibly be responsible is too broad to test one at a time in any reasonable amount of time. This comes up most often for children with unexplained developmental delay, intellectual disability, or multiple birth differences; for families with a condition that clusters in a recognizable but genetically varied pattern, such as certain forms of epilepsy, hearing loss, kidney disease, or hereditary cancer; and, increasingly, for pregnancies where other tests have not explained a finding on ultrasound. In every case, the goal is the same: to search broadly and efficiently for a genetic explanation, rather than testing genes individually based on an educated guess.