The Genome of C57BL/6J "Eve", the Mother of the Laboratory Mouse Genome Reference Strain

Overview

Journal G3 (Bethesda)

Publisher Oxford University Press

Specialties Genetics
Molecular Biology

Date 2019 Apr 19

PMID 30996023

Citations 32

Authors

Vishal Kumar Sarsani

Narayanan Raghupathy

Ian T Fiddes

Joel Armstrong

Francoise Thibaud-Nissen

Oraya Zinder

Mohan Bolisetty

Kerstin Howe

Doug Hinerfeld

Xiaoan Ruan

Lucy Rowe

Mary Barter

Guruprasad Ananda

Benedict Paten

George M Weinstock

Gary A Churchill

Michael V Wiles

Valerie A Schneider

Anuj Srivastava

Laura G Reinholdt

Affiliations

Soon will be listed here.

Abstract

Isogenic laboratory mouse strains enhance reproducibility because individual animals are genetically identical. For the most widely used isogenic strain, C57BL/6, there exists a wealth of genetic, phenotypic, and genomic data, including a high-quality reference genome (GRCm38.p6). Now 20 years after the first release of the mouse reference genome, C57BL/6J mice are at least 26 inbreeding generations removed from GRCm38 and the strain is now maintained with periodic reintroduction of cryorecovered mice derived from a single breeder pair, aptly named Adam and Eve. To provide an update to the mouse reference genome that more accurately represents the genome of today's C57BL/6J mice, we took advantage of long read, short read, and optical mapping technologies to generate a assembly of the C57BL/6J Eve genome (B6Eve). Using these data, we have addressed recurring variants observed in previous mouse genomic studies. We have also identified structural variations, closed gaps in the mouse reference assembly, and revealed previously unannotated coding sequences. This B6Eve assembly explains discrepant observations that have been associated with GRCm38-based analyses, and will inform a reference genome that is more representative of the C57BL/6J mice that are in use today.

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References

Taylor B, Rowe L . Genes for serum amyloid A proteins map to Chromosome 7 in the mouse. Mol Gen Genet. 1984; 195(3):491-9. DOI: 10.1007/BF00341452. View

Cutler G, Marshall L, Chin N, Baribault H, Kassner P . Significant gene content variation characterizes the genomes of inbred mouse strains. Genome Res. 2007; 17(12):1743-54. PMC: 2099583. DOI: 10.1101/gr.6754607. View

Milholland B, Dong X, Zhang L, Hao X, Suh Y, Vijg J . Differences between germline and somatic mutation rates in humans and mice. Nat Commun. 2017; 8:15183. PMC: 5436103. DOI: 10.1038/ncomms15183. View

Beck J, Lloyd S, Hafezparast M, Lennon-Pierce M, Eppig J, Festing M . Genealogies of mouse inbred strains. Nat Genet. 1999; 24(1):23-5. DOI: 10.1038/71641. View

Gurevich A, Saveliev V, Vyahhi N, Tesler G . QUAST: quality assessment tool for genome assemblies. Bioinformatics. 2013; 29(8):1072-5. PMC: 3624806. DOI: 10.1093/bioinformatics/btt086. View

Chin C, Alexander D, Marks P, Klammer A, Drake J, Heiner C . Nonhybrid, finished microbial genome assemblies from long-read SMRT sequencing data. Nat Methods. 2013; 10(6):563-9. DOI: 10.1038/nmeth.2474. View

Zuo B, Du X, Zhao J, Yang H, Wang C, Wu Y . Analysis of microsatellite polymorphism in inbred knockout mice. PLoS One. 2012; 7(4):e34555. PMC: 3324499. DOI: 10.1371/journal.pone.0034555. View

Locke M, Milojevic M, Eitutis S, Patel N, Wishart A, Daley M . Genomic copy number variation in Mus musculus. BMC Genomics. 2015; 16:497. PMC: 4490682. DOI: 10.1186/s12864-015-1713-z. View

Salisbury J . Centrosomes: Sfi1p and centrin unravel a structural riddle. Curr Biol. 2004; 14(1):R27-9. DOI: 10.1016/j.cub.2003.12.019. View

10.

Venkatesh D, Mruk D, Herter J, Cullere X, Chojnacka K, Cheng C . AKAP9, a Regulator of Microtubule Dynamics, Contributes to Blood-Testis Barrier Function. Am J Pathol. 2015; 186(2):270-84. PMC: 4729272. DOI: 10.1016/j.ajpath.2015.10.007. View

11.

Das S, Austin M, Akana M, Deshpande P, Cao H, Xiao M . Single molecule linear analysis of DNA in nano-channel labeled with sequence specific fluorescent probes. Nucleic Acids Res. 2010; 38(18):e177. PMC: 2952877. DOI: 10.1093/nar/gkq673. View

12.

Berlin K, Koren S, Chin C, Drake J, Landolin J, Phillippy A . Assembling large genomes with single-molecule sequencing and locality-sensitive hashing. Nat Biotechnol. 2015; 33(6):623-30. DOI: 10.1038/nbt.3238. View

13.

Graubert T, Cahan P, Edwin D, Selzer R, Richmond T, Eis P . A high-resolution map of segmental DNA copy number variation in the mouse genome. PLoS Genet. 2007; 3(1):e3. PMC: 1761046. DOI: 10.1371/journal.pgen.0030003. View

14.

Beal M, Glenn T, Lance S, Somers C . Characterization of unstable microsatellites in mice: no evidence for germline mutation induction following gamma-radiation exposure. Environ Mol Mutagen. 2012; 53(8):599-607. DOI: 10.1002/em.21726. View

15.

Schimenti K, Feuer S, Griffin L, Graham N, Bovet C, Hartford S . AKAP9 is essential for spermatogenesis and sertoli cell maturation in mice. Genetics. 2013; 194(2):447-57. PMC: 3664854. DOI: 10.1534/genetics.113.150789. View

16.

DePristo M, Banks E, Poplin R, Garimella K, Maguire J, Hartl C . A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nat Genet. 2011; 43(5):491-8. PMC: 3083463. DOI: 10.1038/ng.806. View

17.

Garrison E, Siren J, Novak A, Hickey G, Eizenga J, Dawson E . Variation graph toolkit improves read mapping by representing genetic variation in the reference. Nat Biotechnol. 2018; 36(9):875-879. PMC: 6126949. DOI: 10.1038/nbt.4227. View

18.

Marshall E . Genome sequencing. Public group completes draft of the mouse. Science. 2002; 296(5570):1005. DOI: 10.1126/science.296.5570.1005b. View

19.

Schneider V, Graves-Lindsay T, Howe K, Bouk N, Chen H, Kitts P . Evaluation of GRCh38 and de novo haploid genome assemblies demonstrates the enduring quality of the reference assembly. Genome Res. 2017; 27(5):849-864. PMC: 5411779. DOI: 10.1101/gr.213611.116. View

20.

Fairfield H, Srivastava A, Ananda G, Liu R, Kircher M, Lakshminarayana A . Exome sequencing reveals pathogenic mutations in 91 strains of mice with Mendelian disorders. Genome Res. 2015; 25(7):948-57. PMC: 4484392. DOI: 10.1101/gr.186882.114. View