Genetic heterogeneity of Icelanders

Research undertaken by Professor Einar Árnason at the University of Iceland, Reykjavik and published in the January 2003 issue of Annals of Human Genetics highlights the inaccuracy of claims that Icelanders are a ’genetically homogenous’ population.

Professor Árnason explains in his article: “Recently, statements have been made about a special ’genetic homogeneity’ of the Icelanders that are at variance with earlier work on blood groups and allozymes.” Iceland has been said to be an “island so inbred that it is a happy genetic hunting ground”, ideal for gene mapping, and that “nowhere else has such a pure – and predictable – genetic inheritance” in the popular press. This supposed genetic homogeneity was a major factor in the establishment of deCODE Genetics, the biotechnology company set up in Iceland in 1996 to map disease genes in the Icelandic population. The geographical isolation of the country with little migration for over 1000 years, combined with a series of disasters such as plague and famine, was presumed to have minimized variation in the gene pool. Researchers now suggest that there was a lack of evidence to confirm this homogeneity.

To investigate these claims an extensive reanalysis of mtDNA variation was undertaken by examining primary data from original sources for 26 European populations. The results showed that Icelanders are actually among the most genetically heterogeneous Europeans by the mean number of nucleotide differences, as well as by estimates of parameters of the neutral theory. This is a signature of population admixture during the founding or history of Iceland. Examination of the published literature on blood group and allozyme variation did not provide any support for the notion of special genetic homogeneity of the Icelanders, and further studies of microsatellite variation are unlikely to do so. It is doubtful that population changes during past calamities had much effect on the genetic variability of Icelanders.

Árnason identified anomalies in data used in previous studies that were in some instances due to errors in publicly accessible databases. By reanalysis using primary data from original sources the errors were avoided in this study, and steps were taken to correct them so that they are not propagated in future studies. Árnason concludes “claims about a special genetic homogeneity of Icelanders relative to European populations would be suspect to the extent that they depended on anomalous data instead of the primary data. In any case, one would not expect that meaningful patterns about homogeneity, founder effects and drift in different populations could emerge from analyses whose assumptions are violated and using erroneous data.”

In the same issue of Annals of Human Genetics, in a commentary on the Árnason article, Dr Peter Forster at the University of Cambridge says of the extent of primary data errors in this type of research: “One solution may be for journals to impose more rigorous checks that would discourage hasty submission of manuscripts without adequate proofreading, for example by informing all submitting authors that sequence electropherograms routinely will be checked in the course of the reviewing process. But ultimately, of course, it is up to the authors to ensure the accuracy of their data, and the Icelandic example provides a warning that more care is needed than has been practised in the past.” Dr Forster also warns: “There is no reason to suppose that DNA sequencing errors are restricted to mtDNA. In fact, it is mainly because mtDNA is a non-recombining genetic unit that many errors are easily identified by phylogenetic analysis; errors in nuclear loci or in rapidly mutating loci such as short tandem repeats will be much harder to detect.”