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Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci

by Odom, Duncan, T , European Bioinformatics Institute [Hinxton] (EMBL-EBI) ; EMBL Heidelberg , Fiddes, Ian, T , Czechanski, Anne , BioTuring Inc , Earl, Dent , Shirley, Lesley , Torrance, James , Navarro, Fabio, C. P , Ibarra-Soria, Ximena , Lilue, Jingtao , Stanke, Mario , Pham, Son, K , Reinholdt, Laura , Frankish, Adam , Yang, Fengtang , Yalcin, Binnaz , Universität Greifswald = University of Greifswald , Collins, Stephan , Chow, William , The Jackson Laboratory [Bar Harbor] (JAX) , Nachtweide, Stefanie , Fu, Beiyuan , Wood, Jonathan , Université Bourgogne Franche-Comté [COMUE] (UBFC) , Dolle, Dirk-Dominik , Armstrong, Joel , Loveland, Jane , Paten, Benedict , Collins, Joanna , Howe, Kerstin , Gerstein, Mark , Muir, Paul , Mott, Richard , Goodstadt, Leo , University of California [Los Angeles] (UCLA) ; University of California (UC) , Romoth, Lars , Abrudan, Monica , Flicek, Paul , Doran, Anthony, G , University of Florida [Gainesville] (UF) , University College of London [London] (UCL) , Wong, Kim , Pelan, Sarah , Gilbert, James , Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) ; Université de

in 45/22 / 45/23 / 45/70 / 45/77 / 45/90 / 45/91 / 631/208 / 631/208/191 / 631/208/212 / 631/208/514 / 64/110 / 64/60 / Agriculture / Alleles / Amino acids / Animal genetics / Animal Genetics and Genomics / Animals / Animals, Laboratory / Annotations / Bioinformatics / Biomedical and Life Sciences / Biomedicine / Brain / Cancer Research / Chromosome Mapping - veterinary / Chromosomes / Collaboration / CRISPR / Gene expression / Gene Function / Genes / Genetic Loci / Genetics / Genome / Genomes / Genomics / Haplotypes / Haplotypes - genetics / House mouse / Human Genetics / Immunity / Immunology / Inbreeding / Laboratories / Life Sciences / Loci / Mice / Mice, Inbred BALB C - genetics / Mice, Inbred C3H - genetics / Mice, Inbred C57BL - genetics / Mice, Inbred CBA - genetics / Mice, Inbred DBA - genetics / Mice, Inbred NOD - genetics / Mice, Inbred Strains - classification / Mice, Inbred Strains - genetics / Mitochondrial DNA / Molecular Sequence Annotation / Neural coding / Nucleotide sequence / Phenotypes / Phylogeny / Polymorphism, Single Nucleotide / Proteins / Retrotransposition / Rodents / Species Specificity / Stem cells / Transposons

2018

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2018

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2018

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Journal Article

Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci

Odom, Duncan, T,

European Bioinformatics Institute [Hinxton] (EMBL-EBI) ; EMBL Heidelberg,

Fiddes, Ian, T,

Czechanski, Anne,

BioTuring Inc,

Earl, Dent,

Shirley, Lesley,

Torrance, James,

Navarro, Fabio, C. P,

Ibarra-Soria, Ximena,

Lilue, Jingtao,

Stanke, Mario,

Pham, Son, K,

Reinholdt, Laura,

Frankish, Adam,

Yang, Fengtang,

Yalcin, Binnaz,

Universität Greifswald = University of Greifswald,

Collins, Stephan,

Chow, William,

The Jackson Laboratory [Bar Harbor] (JAX),

Nachtweide, Stefanie,

Fu, Beiyuan,

Wood, Jonathan,

Université Bourgogne Franche-Comté [COMUE] (UBFC),

Dolle, Dirk-Dominik,

Armstrong, Joel,

Loveland, Jane,

Paten, Benedict,

Collins, Joanna,

Howe, Kerstin,

Gerstein, Mark,

Muir, Paul,

Mott, Richard,

Goodstadt, Leo,

University of California [Los Angeles] (UCLA) ; University of California (UC),

Romoth, Lars,

Abrudan, Monica,

Flicek, Paul,

Doran, Anthony, G,

University of Florida [Gainesville] (UF),

University College of London [London] (UCL),

Wong, Kim,

Pelan, Sarah,

Gilbert, James,

Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) ; Université de

2018

Overview

We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development.

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Nature Publishing Group,CCSD,Nature Publishing Group US

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