АвторТема: The Impact of Divergence Time on the Nature of Population Structure... (Iceland)  (Прочитано 2129 раз)

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The Impact of Divergence Time on the Nature of Population Structure: An Example from Iceland

Alkes L. Price1,2,3*, Agnar Helgason4,5*, Snaebjorn Palsson5, Hreinn Stefansson4, David St. Clair6, Ole A. Andreassen7, David Reich3,8, Augustine Kong4, Kari Stefansson4,5*

1 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, 2 Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America, 3 Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America, 4 deCODE Genetics, Reykjavik, Iceland, 5 University of Iceland, Reykjavik, Iceland, 6 Department of Mental Health, University of Aberdeen, Aberdeen, United Kingdom, 7 Division of Psychiatry, Ulleval University Hospital, Oslo, Norway, 8 Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America


Abstract

The Icelandic population has been sampled in many disease association studies, providing a strong motivation to understand the structure of this population and its ramifications for disease gene mapping. Previous work using 40 microsatellites showed that the Icelandic population is relatively homogeneous, but exhibits subtle population structure that can bias disease association statistics. Here, we show that regional geographic ancestries of individuals from Iceland can be distinguished using 292,289 autosomal single-nucleotide polymorphisms (SNPs). We further show that subpopulation differences are due to genetic drift since the settlement of Iceland 1100 years ago, and not to varying contributions from different ancestral populations. A consequence of the recent origin of Icelandic population structure is that allele frequency differences follow a null distribution devoid of outliers, so that the risk of false positive associations due to stratification is minimal. Our results highlight an important distinction between population differences attributable to recent drift and those arising from more ancient divergence, which has implications both for association studies and for efforts to detect natural selection using population differentiation.


Author Summary

The Icelandic population is a structured population, in that geographic regions of Iceland exhibit differences in allele frequencies of genetic markers. Although these differences are relatively small, previous work has shown that they can bias association statistics in disease studies if cases and controls are sampled in different proportions across the geographic regions. In this study, we show that by using dense genotype data it is possible to distinguish the regional geographic ancestry of individuals from Iceland. We further show that the allele frequency differences between regions of Iceland are due to genetic drift since the settling of Iceland, not to differences in contributions from ancestral populations. A consequence of this is that the allele frequency differences follow a null distribution, devoid of unusually large differences caused by the action of natural selection, so that ensuing false positive associations in disease studies will be minimal. This is in stark contrast to populations (such as European Americans) in which subpopulation differences are due to more ancient divergence, allowing the action of natural selection to produce unusually large allele frequency differences that can lead to false positive associations. Our results highlight an important distinction between population differences attributable to recent genetic drift and those arising from more ancient divergence.

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Спасибо за интересную статью, Денис.

В этой статье приводится очень интересная методика по вычислению по частотному распределению аутосомных SNP.Как я показал в своем реферате (правда, на примере Y-STR), подобный статистический метод необходимо использовать в процессе интерпретации данных, полученных после расчетов TMRCA.

 

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