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. 2017 Sep 21:4:170115.
doi: 10.1038/sdata.2017.115.

Whole genome characterization of sequence diversity of 15,220 Icelanders

Hákon Jónsson  1 , Patrick Sulem  1 , Birte Kehr  1 , Snaedis Kristmundsdottir  1 , Florian Zink  1 , Eirikur Hjartarson  1 , Marteinn T Hardarson  1 , Kristjan E Hjorleifsson  1 , Hannes P Eggertsson  1 , Sigurjon Axel Gudjonsson  1 , Lucas D Ward  1 , Gudny A Arnadottir  1 , Einar A Helgason  1 , Hannes Helgason  1 , Arnaldur Gylfason  1 , Adalbjorg Jonasdottir  1 , Aslaug Jonasdottir  1 , Thorunn Rafnar  1 , Soren Besenbacher  2   3 , Michael L Frigge  1 , Simon N Stacey  1 , Olafur Th Magnusson  1 , Unnur Thorsteinsdottir  1   4 , Gisli Masson  1 , Augustine Kong  1   5 , Bjarni V Halldorsson  1   6 , Agnar Helgason  1   7 , Daniel F Gudbjartsson  1   5 , Kari Stefansson  1   4
Affiliations

Whole genome characterization of sequence diversity of 15,220 Icelanders

Hákon Jónsson et al. Sci Data. .

Abstract

Understanding of sequence diversity is the cornerstone of analysis of genetic disorders, population genetics, and evolutionary biology. Here, we present an update of our sequencing set to 15,220 Icelanders who we sequenced to an average genome-wide coverage of 34X. We identified 39,020,168 autosomal variants passing GATK filters: 31,079,378 SNPs and 7,940,790 indels. Calling de novo mutations (DNMs) is a formidable challenge given the high false positive rate in sequencing datasets relative to the mutation rate. Here we addressed this issue by using segregation of alleles in three-generation families. Using this transmission assay, we controlled the false positive rate and identified 108,778 high quality DNMs. Furthermore, we used our extended family structure and read pair tracing of DNMs to a panel of phased SNPs, to determine the parent of origin of 42,961 DNMs.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Schematic overview of the DNM characterization.
Figure 2
Figure 2. The GAM model predicted response for all DNM candidates.
The red line corresponds to the 0.8 GAM response requirement for the high quality DNMs.
Figure 3
Figure 3. The fraction of discordant DNMs between MZ twins.
There were used 91 monozygotic twin pairs for the discordance calculation. The discordance fraction was calculated as the fraction of the proband’s high quality DNMs not found in the MZ twin.
See this image and copyright information in PMC

Dataset use reported in

  • doi: 10.1038/nature24018

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References

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    1. 2017. European Variation Archive. PRJEB15197
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