Oral Presentation Society for Molecular Biology and Evolution Conference 2016

Extreme distribution of deleterious variation in a historically small and isolated population – insights from the Greenlandic Inuit (#86)

Casper-Emil T. Pedersen 1 , Kirk E. Lohmueller 2 , Niels Grarup 3 , Peter Bjerregaard 4 , Torben Hansen 3 , Hans R. Siegismund 1 , Ida Moltke 1 , Anders Albrechtsen 1
  1. Section for Computation and RNA biology (SCARB), Department of Biology, University of Copenhagen, Copenhagen, Denmark
  2. Department of Ecology and Evolutionary Biology, University of California, Los Angeles, United States
  3. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Copenhagen, Denmark
  4. National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark

All non-African human populations have experienced bottlenecks following the expansion of modern humans out of Africa some 60,000 years ago. Recently, several studies of human populations have investigated whether smaller population sizes for out-of-Africa populations lead to less efficient purifying selection and thereby higher genetic load. Given that these studies mainly considered large continental human populations we examine these questions using exome data from 18 Greenlandic Inuit. The Greenlandic Inuit population is particularly interesting to study in this context because it has experienced a ~20,000 year long bottleneck during the last ~25,000 years, making it more extreme than most previously studied populations, such as native Americans, in terms of population size.

When comparing it to a European population, we do not observe a difference in the overall number of deleterious alleles per individual, implying a similar genetic load assuming an additive model. However, we observe a marked difference in the distribution of this load; the Greenlandic Inuit population has fewer variable sites, and thus on average each variable site has a higher load. Also, each variable site has a higher average derived allele frequency. Consequently, the Greenlandic Inuit carry more homozygous derived genotypes and a higher genetic load assuming a recessive model. Despite the long recent bottleneck, we find that selection has still been acting however, it has acted less efficiently.

Our analyses show that the Greenlandic Inuit population has great potential for mapping of disease-causing variants that are rare, and thus difficult to map, in Europeans and other large populations – for both Mendelian and complex diseases. To a certain degree, this characteristic has also been documented for other small populations, yet comparative results for several small populations establish the Greenlandic Inuit as the population with the highest potential for finding novel disease-causing variants.