In human genetics, the identification of the gene responsible for a disease from a knowledge of the underlying molecular defect. If the protein encoded by the gene is known, it is often possible to isolate the appropriate mRNAs and to use them, or cDNAs derived from them, as probes for the gene. This was the first method used successfully to clone genes responsible for certain hereditary diseases, such as sickle cell anemia, Tay-Sachs disease, and phenylketonuria. Contrast with positional cloning. See cDNA, hereditary disease, mRNA, probe.