Positional cloning

Positional cloning has been used to identify
more than 20 human disease genes. The first
and crucial step is clinical identification of the
phenotype. Next, the putative gene is mapped
to a chromosomal position with defined limits
(see B). From here the gene can be isolated
(cloned). In the next step, mutations in the gene
are demonstrated in patients and are shown not
to be present in unaffected family members and
normal controls.
Functional cloning requires prior knowledge of
the function of the gene. As this information is
rarely available at the outset, this approach is
very limited.