Founder effect and genetic disease in Sottunga, Finland

Abstract

Pedigree data are analyzed in order to determine the factors responsible for the high frequencies of certain genetic disorders in an isolated Swedish-speaking population of Finland's A land archipelago. The founders of Sottunga are identified, and the genetic contributions of each founder to descending birth cohorts are estimated. Founders born before 1700 have far more descendants in the contemporary gene pool than do more recent founders. However, because of migration and depopulation since 1900, the expected genetic contributions of the early founders to the present-day population are similar to those of later founders. A descendant in the contemporary population has a 2% chance of having inherited a particular gene from the founder who makes the largest single contribution to the gene pool. This corresponds approximately to a 2% probability of inheriting an autosomal dominant disease gene from this founder. Given an average inbreeding coefficient of 0.0016, the probability of inheriting two recessive disease genes from this founder is 0.000032. The incidence of autosomal dominant von Willebrand disease in Sottunga is greater than 10% while that of autosomal recessive tapetoretinal disease is 1.5%. We conclude, therefore, that the high frequencies of these diseases are not due to the disproportionate genetic contribution of one or a few particular founders. It is more likely that these disease genes occurred in high frequency in the initial population or were introduced repeatedly through time.

Gene Mapping in Isolated Populations: New Roles for Old Friends?

“…However, some of these Baltic islands have experienced considerable sea traffic and may have been less isolated than previously thought [64]. Indeed, the disease haplotype diversity is consistent with genealogical studies that have shown it is extremely unlikely that one or very few founders introduced von Willebrand disease mutations into this population [65, 66]. Because of allelic heterogeneity at the VWF locus, no disequilibrium is observed between the disease phenotype and these polymorphisms [29].…”

The Influence of Past Endogamy and Consanguinity on Genetic Disorders in Northern Sweden

“…Instead, in mainland Finland founder effect and genetic drift originally operating within geographical isolates have been identified as significant factors in the distribution patterns and prevalence of some 36 disease genes, collectively described as the Finnish Disease heritage (Norio, 2003), with random inbreeding due to probably unrecognized remote consanguineous marriages making only a limited contribution to disease gene expression (Papponen et al 1999;Peltonen et al 1999;Norio, 2003). In the studies on theÅland Islands, small effective population size and drift were cited as the primary factors behind the high frequency of recessive disorders (O'Brien et al 1988a(O'Brien et al , 1988b.…”

The Contribution of Irish Immigrants to the Quebec (Canada) Gene Pool: An Estimation Using Data from Deep-Rooted Genealogies

“…The northern part of the country was colonized later by Finnish migrants from the south, with little input from abroad. Several founding events took place, subsequently leading to regional homogeneities and a specific pattern of inherited disorders within the Finnish population (Peltonen et al 1995;Kittles et al 1999;O'Brien et al 1988).…”

“…where S is the sample of subjects linked to the founder, P is the number of genealogical paths between a founder and each subject and g is the number of generations in each path connecting the founder and the subject (Roberts 1968;O'Brien et al 1988;Heyer and Tremblay 1995). Dividing this result by the number of subjects gives the proportion of the subjects' gene pool that comes from that founder.…”