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.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B / genetics*
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Aged
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Aged, 80 and over
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Atrial Fibrillation / genetics
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Bulbar Palsy, Progressive / genetics
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Chromogranins
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Female
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Frameshift Mutation
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GTP-Binding Protein alpha Subunits, Gs / genetics*
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Gene Frequency
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Genetic Predisposition to Disease
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Genome, Human
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Genome-Wide Association Study
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Hearing Loss, Sensorineural / genetics
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Humans
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INDEL Mutation
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Iceland
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Liver Diseases / genetics
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Male
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Middle Aged
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Molecular Sequence Annotation
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Myosin Light Chains / genetics*
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Phylogeography
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Polymorphism, Single Nucleotide
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Receptors, G-Protein-Coupled / genetics
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Risk
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Sequence Analysis, DNA
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Thyrotropin / blood
Substances
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ATP Binding Cassette Transporter, Subfamily B
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Chromogranins
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MYL4 protein, human
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Myosin Light Chains
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Receptors, G-Protein-Coupled
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SLC52A2 protein, human
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Thyrotropin
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multidrug resistance protein 3
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GNAS protein, human
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GTP-Binding Protein alpha Subunits, Gs
Supplementary concepts
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Brown-Vialetto-Van Laere syndrome