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Nat Genet. 2015 May;47(5):435-44. doi: 10.1038/ng.3247. Epub 2015 Mar 25.

Large-scale whole-genome sequencing of the Icelandic population.

Author information

1
1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
2
deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
3
Bioinformatics Research Centre, Aarhus University, C.F. Mollers Alle, Aarhus, Denmark.
4
1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Institute of Biomedical and Neural Engineering, Reykjavík University, Reykjavík, Iceland.
5
1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.
6
Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland.
7
1] Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
8
Department of Internal Medicine, Akureyri Hospital, Akureyri, Iceland.
9
Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland.
10
1] Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali University Hospital, Reykjavik, Iceland.
11
Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali University Hospital, Reykjavik, Iceland.
12
1] Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, Iceland.
13
Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavik, Iceland.
14
1] Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland. [3] Icelandic Cancer Registry, Reykjavik, Iceland.
15
1] Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. [2] Department of Genetics and Molecular Medicine, Landspitali University Hospital, Reykjavik, Iceland.
16
Department of Pediatrics, Section of Child Neurology, The Children's Hospital of Reykjavik, Landspitali University Hospital, Reykjavik, Iceland.
17
Icelandic Medical Center (Laeknasetrid), Laboratory in Mjodd (RAM), Reykjavik, Iceland.
18
Department of Clinical Biochemistry, Akureyri Hospital, Akureyri, Iceland.
19
Department of Clinical Biochemistry, Landspitali University Hospital, Reykjavik, Iceland.
20
1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
21
1] deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. [2] Department of Anthropology, University of Iceland, Reykjavik, Iceland.

Abstract

Here we describe the insights gained from sequencing the whole genomes of 2,636 Icelanders to a median depth of 20×. We found 20 million SNPs and 1.5 million insertions-deletions (indels). We describe the density and frequency spectra of sequence variants in relation to their functional annotation, gene position, pathway and conservation score. We demonstrate an excess of homozygosity and rare protein-coding variants in Iceland. We imputed these variants into 104,220 individuals down to a minor allele frequency of 0.1% and found a recessive frameshift mutation in MYL4 that causes early-onset atrial fibrillation, several mutations in ABCB4 that increase risk of liver diseases and an intronic variant in GNAS associating with increased thyroid-stimulating hormone levels when maternally inherited. These data provide a study design that can be used to determine how variation in the sequence of the human genome gives rise to human diversity.

PMID:
25807286
DOI:
10.1038/ng.3247
[Indexed for MEDLINE]

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