The Effect of an Extreme and Prolonged Population Bottleneck on Patterns of Deleterious Variation: Insights from the Greenlandic Inuit

Casper-Emil T Pedersen, Kirk E Lohmueller, Niels Grarup, Peter Bjerregaard, Torben Hansen, Hans R Siegismund, Ida Moltke, Anders Albrechtsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The genetic consequences of population bottlenecks on patterns of deleterious genetic variation in human populations are of tremendous interest. Based on exome sequencing of 18 Greenlandic Inuit here we show that the Inuit have undergone a severe ~20,000 year long bottleneck. This has led to a markedly more extreme distribution of allele frequencies than seen for any other human population, making the Inuit the perfect population for investigating the effect of a bottleneck on patterns of deleterious variation. When comparing proxies for genetic load that assume an additive effect of deleterious alleles, the Inuit show, at most, a slight increase in load compared to European, East Asian, and African populations. Specifically, we observe < 4% increase in the number of derived deleterious alleles in the Inuit. In contrast, proxies for genetic load under a recessive model suggest that the Inuit have a significantly higher load (20% increase or more) compared to other less bottlenecked human populations. Forward simulations under realistic models of demography support our empirical findings, showing up to a 6% increase in the genetic load for the Inuit population across all models of dominance. Interestingly, these simulations had similar numbers of derived deleterious alleles across populations, suggesting that this statistic is not an ideal approximation to genetic load. Overall, our results show how recent demographic history has affected patterns of deleterious variants in human populations.

Original languageEnglish
JournalGenetics
Volume205
Issue number2
Pages (from-to)787-801
ISSN0016-6731
DOIs
Publication statusPublished - 2017

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