title: Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios.
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.
authors.affiliation: Bioinformatics Research Center, Aarhus University, C. F. Møllers Allé 8, DK-8000 Aarhus, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Besenbacher
authors.affiliation: 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.
authors.forename: Siyang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: José M G
authors.initials: JM
authors.lastname: Izarzugaza
authors.affiliation: 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.
authors.forename: Jakob
authors.initials: J
authors.lastname: Grove
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Belling
authors.affiliation: 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.
authors.forename: Jette
authors.initials: J
authors.lastname: Bork-Jensen
authors.affiliation: 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.
authors.forename: Shujia
authors.initials: S
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Als
authors.affiliation: 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.
authors.forename: Shengting
authors.initials: S
authors.lastname: Li
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: Rachita
authors.initials: R
authors.lastname: Yadav
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: Arcadio
authors.initials: A
authors.lastname: Rubio-García
authors.affiliation: 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.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lescai
authors.affiliation: 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.
authors.forename: Ditte
authors.initials: D
authors.lastname: Demontis
authors.affiliation: BGI Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Junhua
authors.initials: J
authors.lastname: Rao
authors.affiliation: BGI Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Weijian
authors.initials: W
authors.lastname: Ye
authors.affiliation: 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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mailund
authors.affiliation: 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.
authors.forename: Rune M
authors.initials: RM
authors.lastname: Friborg
authors.affiliation: Bioinformatics Research Center, Aarhus University, C. F. Møllers Allé 8, DK-8000 Aarhus, Denmark.
authors.forename: Christian N S
authors.initials: CN
authors.lastname: Pedersen
authors.affiliation: BGI Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Ruiqi
authors.initials: R
authors.lastname: Xu
authors.affiliation: BGI Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Jihua
authors.initials: J
authors.lastname: Sun
authors.affiliation: BGI Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: BGI Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.affiliation: BGI Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: David
authors.initials: D
authors.lastname: Flores
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: Emil
authors.initials: E
authors.lastname: Rydza
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Rapacki
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: John
authors.initials: J
authors.lastname: Damm Sørensen
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: Piotr
authors.initials: P
authors.lastname: Chmura
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: David
authors.initials: D
authors.lastname: Westergaard
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: Piotr
authors.initials: P
authors.lastname: Dworzynski
authors.affiliation: 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.
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Lund
authors.affiliation: 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.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: BGI Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.affiliation: BGI Europe, Ole Maaløes Vej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Lars
authors.initials: L
authors.lastname: Bolund
authors.affiliation: 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.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: Department of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Eiberg
authors.affiliation: 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.
authors.forename: Anders
authors.initials: A
authors.lastname: Krogh
authors.affiliation: 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.
authors.forename: Anders D
authors.initials: AD
authors.lastname: Børglum
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Brunak
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: 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.
authors.forename: Mikkel H
authors.initials: MH
authors.lastname: Schierup
authors.affiliation: 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.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: Ramneek
authors.initials: R
authors.lastname: Gupta
authors.affiliation: 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.
authors.forename: Palle
authors.initials: P
authors.lastname: Villesen
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet 208, DK-2800 Kgs Lyngby, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Rasmussen
mesh_terms: D000465:Algorithms; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D059645:Mutation Rate; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods