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      Uncovering the Genetic History of the Present-Day Greenlandic Population

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          Abstract

          Because of past limitations in samples and genotyping technologies, important questions about the history of the present-day Greenlandic population remain unanswered. In an effort to answer these questions and in general investigate the genetic history of the Greenlandic population, we analyzed ∼200,000 SNPs from more than 10% of the adult Greenlandic population (n = 4,674). We found that recent gene flow from Europe has had a substantial impact on the population: more than 80% of the Greenlanders have some European ancestry (on average ∼25% of their genome). However, we also found that the amount of recent European gene flow varies across Greenland and is far smaller in the more historically isolated areas in the north and east and in the small villages in the south. Furthermore, we found that there is substantial population structure in the Inuit genetic component of the Greenlanders and that individuals from the east, west, and north can be distinguished from each other. Moreover, the genetic differences in the Inuit ancestry are consistent with a single colonization wave of the island from north to west to south to east. Although it has been speculated that there has been historical admixture between the Norse Vikings who lived in Greenland for a limited period ∼600–1,000 years ago and the Inuit, we found no evidence supporting this hypothesis. Similarly, we found no evidence supporting a previously hypothesized admixture event between the Inuit in East Greenland and the Dorset people, who lived in Greenland before the Inuit.

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          Ancient human genome sequence of an extinct Palaeo-Eskimo.

          We report here the genome sequence of an ancient human. Obtained from approximately 4,000-year-old permafrost-preserved hair, the genome represents a male individual from the first known culture to settle in Greenland. Sequenced to an average depth of 20x, we recover 79% of the diploid genome, an amount close to the practical limit of current sequencing technologies. We identify 353,151 high-confidence single-nucleotide polymorphisms (SNPs), of which 6.8% have not been reported previously. We estimate raw read contamination to be no higher than 0.8%. We use functional SNP assessment to assign possible phenotypic characteristics of the individual that belonged to a culture whose location has yielded only trace human remains. We compare the high-confidence SNPs to those of contemporary populations to find the populations most closely related to the individual. This provides evidence for a migration from Siberia into the New World some 5,500 years ago, independent of that giving rise to the modern Native Americans and Inuit.
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            SNP Calling, Genotype Calling, and Sample Allele Frequency Estimation from New-Generation Sequencing Data

            We present a statistical framework for estimation and application of sample allele frequency spectra from New-Generation Sequencing (NGS) data. In this method, we first estimate the allele frequency spectrum using maximum likelihood. In contrast to previous methods, the likelihood function is calculated using a dynamic programming algorithm and numerically optimized using analytical derivatives. We then use a Bayesian method for estimating the sample allele frequency in a single site, and show how the method can be used for genotype calling and SNP calling. We also show how the method can be extended to various other cases including cases with deviations from Hardy-Weinberg equilibrium. We evaluate the statistical properties of the methods using simulations and by application to a real data set.
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              The genetic prehistory of the New World Arctic.

              The New World Arctic, the last region of the Americas to be populated by humans, has a relatively well-researched archaeology, but an understanding of its genetic history is lacking. We present genome-wide sequence data from ancient and present-day humans from Greenland, Arctic Canada, Alaska, Aleutian Islands, and Siberia. We show that Paleo-Eskimos (~3000 BCE to 1300 CE) represent a migration pulse into the Americas independent of both Native American and Inuit expansions. Furthermore, the genetic continuity characterizing the Paleo-Eskimo period was interrupted by the arrival of a new population, representing the ancestors of present-day Inuit, with evidence of past gene flow between these lineages. Despite periodic abandonment of major Arctic regions, a single Paleo-Eskimo metapopulation likely survived in near-isolation for more than 4000 years, only to vanish around 700 years ago. Copyright © 2014, American Association for the Advancement of Science.
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                Author and article information

                Contributors
                Journal
                Am J Hum Genet
                Am. J. Hum. Genet
                American Journal of Human Genetics
                Elsevier
                0002-9297
                1537-6605
                08 January 2015
                31 December 2014
                : 96
                : 1
                : 54-69
                Affiliations
                [1 ]The Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark
                [2 ]Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA
                [3 ]Department of Integrative Biology, University of California, Berkeley, Berkeley, CA 94720, USA
                [4 ]UCL Genetics Institute, Department of Genetics, Evolution, and Environment, University College London, London WC1E 6BT, UK
                [5 ]Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen, Denmark
                [6 ]National Institute of Public Health, University of Southern Denmark, 1353 Copenhagen, Denmark
                [7 ]Steno Diabetes Center, 2820 Gentofte, Denmark
                [8 ]The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark
                [9 ]Arctic Centre at the Ethnographic Collections, National Museum of Denmark, 1220 Copenhagen, Denmark
                [10 ]Research Centre for Prevention and Health, Glostrup University Hospital, 2600 Glostrup, Denmark
                [11 ]Department of Clinical Experimental Research, Glostrup University Hospital, 2600 Glostrup, Denmark
                [12 ]Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
                [13 ]Faculty of Health Sciences, University of Southern Denmark, 5000 Odense, Denmark
                [14 ]Department of Statistics, University of California, Berkeley, Berkeley, CA 94720, USA
                Author notes
                []Corresponding author rasmus_nielsen@ 123456berkeley.edu
                [∗∗ ]Corresponding author albrecht@ 123456binf.ku.dk
                Article
                S0002-9297(14)00478-9
                10.1016/j.ajhg.2014.11.012
                4289681
                25557782
                486efd96-dc07-4160-9df3-506283a24e09
                ©2015 by The American Society of Human Genetics. All rights reserved.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 September 2014
                : 20 November 2014
                Categories
                Article

                Genetics
                Genetics

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