reference genome

A reference genome is a standard, agreed-upon version of a species' DNA sequence that scientists use as a yardstick. Think of it as the master copy of a map: when you sequence an individual, you line your reads up against the reference to see where they fit and how they differ.

Comparing a person's sequence to the reference is what makes finding variants practical. Each short read is matched to its corresponding spot on the reference, and any positions where the individual's bases differ are flagged as variants — single-base changes, small insertions or deletions, and so on.

An important caveat is that a reference genome is not a single 'perfect' or 'normal' human. Early references were assembled from a handful of donors and inevitably miss variation common in other populations, which can bias analysis. To address this, researchers are moving toward a pangenome — a reference built from many people that better captures human diversity.