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PMID: 30996023 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

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

G3 (Bethesda, Md.) ·Vol. 9 ·No. 6 ·2019-00-05 ·Pages 1795-1805

Sarsani VK, Raghupathy N, Fiddes IT, Armstrong J, Thibaud-Nissen F, Zinder O, Bolisetty M, Howe K, Hinerfeld D, Ruan X, Rowe L, Barter M, Ananda G, Paten B, Weinstock GM, Churchill GA, Wiles MV, Schneider VA, Srivastava A, Reinholdt LG

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 de novo 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.

Keywords
C57BL/6J Mus musculus domesticus de novo genome assembly laboratory mouse long read sequencing reference genomes reproducibility
MeSH Terms
Animals Computational Biology/methods Female Genome Genomics/methods Inbreeding Male Mice Mice, Inbred C57BL Pedigree Phenotype Polymorphism, Single Nucleotide
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Sarsani Vishal Kumar
The Jackson Laboratory for Mammalian Genetics, Bar Harbor ME.
Raghupathy Narayanan
The Jackson Laboratory for Mammalian Genetics, Bar Harbor ME.
Fiddes Ian T
UC Santa Cruz Genomics Institute, Santa Cruz, California, Department of Biomolecular Engineering, University of California, Santa Cruz, California.
Armstrong Joel
UC Santa Cruz Genomics Institute, Santa Cruz, California, Department of Biomolecular Engineering, University of California, Santa Cruz, California.
Thibaud-Nissen Francoise
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894.
Zinder Oraya
The Jackson Laboratory for Mammalian Genetics, Bar Harbor ME.
Bolisetty Mohan
The Jackson Laboratory for Mammalian Genetics, Bar Harbor ME.
Howe Kerstin
Wellcome Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
Hinerfeld Doug
NanoString Technologies, Inc, and.
Ruan Xiaoan
The Jackson Laboratory for Genomic Medicine, Farmington, CT.
Rowe Lucy
The Jackson Laboratory for Mammalian Genetics, Bar Harbor ME.
Barter Mary
The Jackson Laboratory for Mammalian Genetics, Bar Harbor ME.
Ananda Guruprasad
The Jackson Laboratory for Genomic Medicine, Farmington, CT.
Paten Benedict
UC Santa Cruz Genomics Institute, Santa Cruz, California, Department of Biomolecular Engineering, University of California, Santa Cruz, California.
Weinstock George M
The Jackson Laboratory for Genomic Medicine, Farmington, CT.
Churchill Gary A
The Jackson Laboratory for Mammalian Genetics, Bar Harbor ME.
Wiles Michael V
The Jackson Laboratory for Mammalian Genetics, Bar Harbor ME.
Schneider Valerie A
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894.
Srivastava Anuj ORCID
The Jackson Laboratory for Genomic Medicine, Farmington, CT [email protected] [email protected].
Reinholdt Laura G ORCID
The Jackson Laboratory for Mammalian Genetics, Bar Harbor ME [email protected] [email protected].
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Article Info
Journal
G3 (Bethesda, Md.)
Abbr.
G3 (Bethesda)
ISSN
2160-1836
DOI
10.1534/g3.119.400071
Email
[email protected]
[email protected]
Published
2019-00-05
Epub
2019-00-05
Pages
1795-1805
Language
English
Region
England
NLM ID
101566598
PMCID
PMC6553538
Subset
IM
Grants
NCI NIH HHS · P30 CA034196 · United States
NIH HHS · R24 OD021325 · United States
NIH HHS · U42 OD010921 · United States
External Links
PubMed source DOI: 10.1534/g3.119.400071 PMC Full Text View journal details
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