Multiple mutations responsible for frequent genetic diseases in isolated populations.

The relatively frequent existence of an autosomal recessive disease in an isolated population suggests a founder effect. However, in many cases the high frequency is due to more than one mutation in either one or several genes. Several possibilities have been raised to explain these findings: a chance phenomenon, migration of families with affected patients or digenic inheritance. Although each of these possibilities may be responsible for a few of the cases, in most they are very improbable explanations. A selective advantage may explain most of the observations even if it is difficult to prove.