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Population substructure in Finland and Sweden revealed by the use of spatial coordinates and a small number of unlinked autosomal SNPs.

Hannelius U, Salmela E, Lappalainen T, Guillot G, Lindgren CM, von Döbeln U, Lahermo P, Kere J - BMC Genet. (2008)

Bottom Line: However, some studies have suggested that this number could be reduced if the individual spatial coordinates are taken into account in the analysis.In Sweden, we found a deficit of heterozygotes that we could explain by simulation studies to be due to both a small non-random genotyping error and hidden substructure caused by immigration.We also demonstrate the importance of estimating the size and effect of genotyping error in population genetics in order to strengthen the validity of the results.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, 14157 Huddinge, Sweden. ulf.hannelius@ki.se

ABSTRACT

Background: Despite several thousands of years of close contacts, there are genetic differences between the neighbouring countries of Finland and Sweden. Within Finland, signs of an east-west duality have been observed, whereas the population structure within Sweden has been suggested to be more subtle. With a fine-scale substructure like this, inferring the cluster membership of individuals requires a large number of markers. However, some studies have suggested that this number could be reduced if the individual spatial coordinates are taken into account in the analysis.

Results: We genotyped 34 unlinked autosomal single nucleotide polymorphisms (SNPs), originally designed for zygosity testing, from 2044 samples from Sweden and 657 samples from Finland, and 30 short tandem repeats (STRs) from 465 Finnish samples. We saw significant population structure within Finland but not between the countries or within Sweden, and isolation by distance within Finland and between the countries. In Sweden, we found a deficit of heterozygotes that we could explain by simulation studies to be due to both a small non-random genotyping error and hidden substructure caused by immigration. Geneland, a model-based Bayesian clustering algorithm, clustered the individuals into groups that corresponded to Sweden and Eastern and Western Finland when spatial coordinates were used, whereas in the absence of spatial information, only one cluster was inferred.

Conclusion: We show that the power to cluster individuals based on their genetic similarity is increased when including information about the spatial coordinates. We also demonstrate the importance of estimating the size and effect of genotyping error in population genetics in order to strengthen the validity of the results.

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Simulations of genotyping error and hidden population structure in Sweden. The simulated effect of genotyping error and hidden population structure on the total fixation index Findividual/country (FIT) and the number of markers deviating from HWE in the Swedish data. The 95% confidence bounds are based on 1,000 simulations. A) Non-random error and non-European substructure, B) random error and non-European substructure, C) non-random error and European substructure, D) random error and European substructure.
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Figure 4: Simulations of genotyping error and hidden population structure in Sweden. The simulated effect of genotyping error and hidden population structure on the total fixation index Findividual/country (FIT) and the number of markers deviating from HWE in the Swedish data. The 95% confidence bounds are based on 1,000 simulations. A) Non-random error and non-European substructure, B) random error and non-European substructure, C) non-random error and European substructure, D) random error and European substructure.

Mentions: To estimate the relative role of these factors, we performed a simulation modeling the effect of immigration (European or non-European) or genotyping error (random or non-random) on F-statistic inflation and HWE deviations. The results (Figure 4) showed that random error and European immigration, either alone or in combination, could not account for the observed amount of deviations (Figure 4D), and that the observations fit best with a combination of both genotyping error and non-European ancestry (4% when the error is non-random and 10% when random) (Figure 4A–B). These levels of immigration correspond well to the situation in Sweden, where in 2003 approximately 16% of the inhabitants had a foreign background [see Additional file 7], and of them about 40% were non-Europeans (Statistics Sweden, ).


Population substructure in Finland and Sweden revealed by the use of spatial coordinates and a small number of unlinked autosomal SNPs.

Hannelius U, Salmela E, Lappalainen T, Guillot G, Lindgren CM, von Döbeln U, Lahermo P, Kere J - BMC Genet. (2008)

Simulations of genotyping error and hidden population structure in Sweden. The simulated effect of genotyping error and hidden population structure on the total fixation index Findividual/country (FIT) and the number of markers deviating from HWE in the Swedish data. The 95% confidence bounds are based on 1,000 simulations. A) Non-random error and non-European substructure, B) random error and non-European substructure, C) non-random error and European substructure, D) random error and European substructure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2527025&req=5

Figure 4: Simulations of genotyping error and hidden population structure in Sweden. The simulated effect of genotyping error and hidden population structure on the total fixation index Findividual/country (FIT) and the number of markers deviating from HWE in the Swedish data. The 95% confidence bounds are based on 1,000 simulations. A) Non-random error and non-European substructure, B) random error and non-European substructure, C) non-random error and European substructure, D) random error and European substructure.
Mentions: To estimate the relative role of these factors, we performed a simulation modeling the effect of immigration (European or non-European) or genotyping error (random or non-random) on F-statistic inflation and HWE deviations. The results (Figure 4) showed that random error and European immigration, either alone or in combination, could not account for the observed amount of deviations (Figure 4D), and that the observations fit best with a combination of both genotyping error and non-European ancestry (4% when the error is non-random and 10% when random) (Figure 4A–B). These levels of immigration correspond well to the situation in Sweden, where in 2003 approximately 16% of the inhabitants had a foreign background [see Additional file 7], and of them about 40% were non-Europeans (Statistics Sweden, ).

Bottom Line: However, some studies have suggested that this number could be reduced if the individual spatial coordinates are taken into account in the analysis.In Sweden, we found a deficit of heterozygotes that we could explain by simulation studies to be due to both a small non-random genotyping error and hidden substructure caused by immigration.We also demonstrate the importance of estimating the size and effect of genotyping error in population genetics in order to strengthen the validity of the results.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, 14157 Huddinge, Sweden. ulf.hannelius@ki.se

ABSTRACT

Background: Despite several thousands of years of close contacts, there are genetic differences between the neighbouring countries of Finland and Sweden. Within Finland, signs of an east-west duality have been observed, whereas the population structure within Sweden has been suggested to be more subtle. With a fine-scale substructure like this, inferring the cluster membership of individuals requires a large number of markers. However, some studies have suggested that this number could be reduced if the individual spatial coordinates are taken into account in the analysis.

Results: We genotyped 34 unlinked autosomal single nucleotide polymorphisms (SNPs), originally designed for zygosity testing, from 2044 samples from Sweden and 657 samples from Finland, and 30 short tandem repeats (STRs) from 465 Finnish samples. We saw significant population structure within Finland but not between the countries or within Sweden, and isolation by distance within Finland and between the countries. In Sweden, we found a deficit of heterozygotes that we could explain by simulation studies to be due to both a small non-random genotyping error and hidden substructure caused by immigration. Geneland, a model-based Bayesian clustering algorithm, clustered the individuals into groups that corresponded to Sweden and Eastern and Western Finland when spatial coordinates were used, whereas in the absence of spatial information, only one cluster was inferred.

Conclusion: We show that the power to cluster individuals based on their genetic similarity is increased when including information about the spatial coordinates. We also demonstrate the importance of estimating the size and effect of genotyping error in population genetics in order to strengthen the validity of the results.

Show MeSH
Related in: MedlinePlus