Ribonucleic acid (RNA) is extracted from the FMD virus and part of it (usually a region corresponding to all or part of the VP1 protein) is transcribed as deoxyribonucleic acid (DNA), which is then sequenced.

The nucleic acid sequence generated is compared with those of other virus isolates to determine the degree of relationship. Often, the relationships are expressed as computer-generated maps or dendograms.

Although usually reliable, nucleic acid sequences do not necessarily relate to antigenicity and the significance of the data will also depend on the length and region of RNA transcribed into DNA.