ABSTRACT
Positional cloning is much more likely to identify novel genetic effects than
candidate gene studies. Genetic linkage studies are very powerful for the study of single gene disorders, but have limited power in complex genetic
disorders when many genes are likely to be acting and there is no estab-
lished model for the inheritance of a given disease. Genetic linkage studies
in a complex disorder such as asthma typically give an imprecise signal for
the localization of the diseased gene that may extend over tens of megabases
of DNA. This is because only a proportion of families will actually be
linked to the locus, while others will appear randomly linked and nonlinked.
In addition, the proportion of individuals with susceptibility alleles who develop the disease will vary between families (i.e., the alleles will have vari-
able penetrance). For this reason, even highly ambitious genetic linkage
studies involving several hundreds of families have often failed to deliver
conclusive results.
