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

Abstract

The genealogic origin of steroid 21-hydroxylase gene (CYP21) mutations and associated haplotypes was determined in 74 unrelated Finnish families with CYP21 deficiency (congenital adrenal hyperplasia, CAH). These families account for two thirds (85/119) of all diagnosed patients of Finnish descent found in this country. We recently demonstrated that multiple founder mutations each associated with a particular haplotype can be found in Finland. Interestingly, some of the haplotypes were identical to those observed in various 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 particular 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 diseases 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 origin 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 haplotype is frequent in many European patient populations, we provide independent genetic evidence of this Iron Age immigration. On the other hand, another frequent haplotype found solely in Finland reflects a more recent (post 15th century) settlement expansion. Consequently, well characterised and sufficiently frequent autosomal gene markers can provide useful information on migrations both between and within populations.

Molecular Defects of the <i>CYP21A2</i> Gene in Greek-Cypriot Patients with Congenital Adrenal Hyperplasia

“…The overall frequency of p.V281L is however one of the highest found for this mutation both in Greek [18] and other populations in Europe and the Mediterranean area [19,20,21,22,25,35,36,48,49,50,51]. This mutation is quite common in our population.…”

Human Population Genetics: Lessons from Finland

“…Especially illustrative are the results on steroid 21-hydroxylase gene (CYP21) mutations (45,46). Homozygous CYP21 deficiency causes congenital adrenal hyperplasia and virilization in girls.…”

Probable identity-by-descent for a mutation in the Dyggve-Melchior-Clausen/Smith-McCort dysplasia (Dymeclin) gene among patients from Guam, Chile, Argentina, and Spain

“…Others have tracked the origins of mutations based on frequency gradients of the associated haplotypes [Levo et al, 1999;Lucotte, 2001], or used common haplotypes to suggest relationships among families [Le Bizec et al, 2005]. These models imply that rare mutations mark specific haplotypes, thereby allowing historical population migrations to be traced.…”