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Nat Commun. 2015 Jan 19;6:5969. doi: 10.1038/ncomms6969.

Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios.

Author information

1
Bioinformatics Research Center, Aarhus University, C. F. Møllers Allé 8, DK-8000 Aarhus, Denmark.
2
1] BGI Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark [2] Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark.
3
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
4
1] Bioinformatics Research Center, Aarhus University, C. F. Møllers Allé 8, DK-8000 Aarhus, Denmark [2] Centre for Integrative Sequencing, iSEQ, Aarhus University, Bartholins Allé 6, building 1242, DK-8000 Aarhus, Denmark [3] The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, DK-8000 Aarhus, Denmark [4] Department of Biomedicine, Aarhus University, Bartholins Allé 6, building 1242, DK-8000 Aarhus, Denmark.
5
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1-3, DK-2100 Copenhagen, Denmark.
6
1] BGI Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark [2] School of Bioscience and Biotechnology, South China University of Technology, Guangzhou 510006, China.
7
1] Centre for Integrative Sequencing, iSEQ, Aarhus University, Bartholins Allé 6, building 1242, DK-8000 Aarhus, Denmark [2] The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, DK-8000 Aarhus, Denmark [3] Department of Biomedicine, Aarhus University, Bartholins Allé 6, building 1242, DK-8000 Aarhus, Denmark.
8
1] BGI Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark [2] Centre for Integrative Sequencing, iSEQ, Aarhus University, Bartholins Allé 6, building 1242, DK-8000 Aarhus, Denmark [3] The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, DK-8000 Aarhus, Denmark [4] Department of Biomedicine, Aarhus University, Bartholins Allé 6, building 1242, DK-8000 Aarhus, Denmark.
9
BGI Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark.
10
1] Bioinformatics Research Center, Aarhus University, C. F. Møllers Allé 8, DK-8000 Aarhus, Denmark [2] Centre for Integrative Sequencing, iSEQ, Aarhus University, Bartholins Allé 6, building 1242, DK-8000 Aarhus, Denmark.
11
1] The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1-3, DK-2100 Copenhagen, Denmark [2] Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Nordre Fasanvej 57, Hovedvejen 5, DK2000 Copenhagen, Denmark.
12
1] The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1-3, DK-2100 Copenhagen, Denmark [2] Faculty of Health Sciences, University of Southern Denmark, DK-5000 Odense, Denmark.
13
1] Centre for Integrative Sequencing, iSEQ, Aarhus University, Bartholins Allé 6, building 1242, DK-8000 Aarhus, Denmark [2] Department of Biomedicine, Aarhus University, Bartholins Allé 6, building 1242, DK-8000 Aarhus, Denmark.
14
Department of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
15
1] Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark [2] Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, DK-1350 Copenhagen, Denmark.
16
Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark.
17
1] BGI Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark [2] Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark [3] Centre for Integrative Sequencing, iSEQ, Aarhus University, Bartholins Allé 6, building 1242, DK-8000 Aarhus, Denmark.

Abstract

Building a population-specific catalogue of single nucleotide variants (SNVs), indels and structural variants (SVs) with frequencies, termed a national pan-genome, is critical for further advancing clinical and public health genetics in large cohorts. Here we report a Danish pan-genome obtained from sequencing 10 trios to high depth (50 × ). We report 536k novel SNVs and 283k novel short indels from mapping approaches and develop a population-wide de novo assembly approach to identify 132k novel indels larger than 10 nucleotides with low false discovery rates. We identify a higher proportion of indels and SVs than previous efforts showing the merits of high coverage and de novo assembly approaches. In addition, we use trio information to identify de novo mutations and use a probabilistic method to provide direct estimates of 1.27e-8 and 1.5e-9 per nucleotide per generation for SNVs and indels, respectively.

PMID:
25597990
PMCID:
PMC4309431
DOI:
10.1038/ncomms6969
[Indexed for MEDLINE]
Free PMC Article

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