Messages from an isolate: lessons from the Finnish gene pool.

Abstract

Genetic isolates are the result of some type of bottleneck in the history of a population, revealing the consequences of the founder effect and genetic drift on the population's gene pool. In human populations, isolation is suspected based on an exceptional geographic location or cultural history or on the prevalence of relatively rare genetic diseases. The concept of 'Finnish disease heritage' is well established in the literature, but solid data have only recently emerged regarding the uniformity of disease mutations at the molecular level in this population: for many Finnish diseases for which the molecular defect has been uncovered, over 90% of disease alleles carry the same causative mutation. This suggests dramatic isolation, especially in some subregions of the sparsely populated country. In Finland, this molecular information can be combined with the exceptional genealogical data offered by a well established church record system which dates back to 1640, containing detailed information on births, deaths, marriages and movements of the majority of the population. This provides excellent opportunities for special study designs for the identification not only of rare disease genes but also of major loci which contribute to complex diseases. The utilization of linkage disequilibrium and the search for shared haplotypes can be justified in subpopulations and patient materials from this genetic isolate. This review summarizes the current molecular evidence for genetic isolation as well as the utilization of some special strategies in the disease gene hunt in the Finnish population.