Tracing past population migrations: genealogy of steroid 21-hydroxylase (CYP21) gene mutations in Finland

The genealogic origin of steroid 21-hydroxylase gene (CYP21) mutations and associated haplotypes was determined in 74 unrelated Finnish families,vith CYP21 deficiency (congenital adrenal hyperplasia, CAH). These families acco unt for two thirds (85/119) of all diagnosed patients of Finnish descent fo und in this country, We recently demonstrated that multiple founder mutatio ns each associated,vith a particular haplotype can be found in Finland, Int erestingly, some of the haplotypes were identical to those observed in vari ous European populations, whereas others have not been described elsewhere, indicating a local and perhaps a more recent origin. In the present report we show that each of the major founder haplotypes originates from a partic ular geographic region of Finland, Thus many local genetic isolates are to be expected in Finland, Our finding is in a clear contrast to the genetic d iseases known as the 'Finnish disease heritage', in which only one mutation usually predominates. Some of the CYP21 haplotypes proved very informative for analysis of the history of the Finnish population, For example, the or igin of one frequent haplotype was shown to cluster in a region assumed by archaeological data to be a major site of immigration by settlers of either Scandinavian or Baltic origin during the first centuries AD. As this haplo type is frequent in many European patient populations, we provide independe nt genetic evidence of this Iron Age immigration, On the other hand, anothe r frequent haplotype found solely in Finland reflects a more recent (post 1 5th century) settlement expansion, Consequently, well characterised and suf ficiently frequent autosomal gene markers can provide useful information on migrations both between and within populations.