A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains

M. M. Simon; S. Greenaway; J. K. White; H. Fuchs; V. Gailus-Durner; S. Wells; T. Sorg; K. Wong; E. Bedu; E. J. Cartwright; R. Dacquin; S. Djebali; J. Estabel; J. Graw; N. J. Ingham; I. J. Jackson; A. Lengeling; S. Mandillo; J. Marvel; H. Meziane; F. Preitner; O. Puk; M. Roux; D. J. Adams; S. Atkins; A. Ayadi; L. Becker; A. Blake; D. Brooker; H. Cater; M. F. Champy; R. Combe; P. Danecek; A. di Fenza; H. Gates; A. K. Gerdin; E. Golini; J. M. Hancock; W. Hans; S. M. Holter; T. Hough; P. Jurdic; T. M. Keane; H. Morgan; W. Muller; F. Neff; G. Nicholson; B. Pasche; L. A. Roberson; J. Rozman; M. Sanderson; L. Santos; M. Selloum; C. Shannon; A. Southwell; G. P. Tocchini-Valentini; V. E. Vancollie; H. Westerberg; W. Wurst; M. Zi; B. Yalcin; R. Ramirez-Solis; K. P. Steel; A. M. Mallon; M. H. de Angelis; Y. Herault; S. D. M. Brown

doi:10.1186/gb-2013-14-7-r82

A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains

M. M. Simon, S. Greenaway, J. K. White, H. Fuchs, V. Gailus-Durner, S. Wells, T. Sorg, K. Wong, E. Bedu, E. J. Cartwright, R. Dacquin, S. Djebali, J. Estabel, J. Graw, N. J. Ingham, I. J. Jackson, A. Lengeling, S. Mandillo, J. Marvel, H. MezianeF. Preitner, O. Puk, M. Roux, D. J. Adams, S. Atkins, A. Ayadi, L. Becker, A. Blake, D. Brooker, H. Cater, M. F. Champy, R. Combe, P. Danecek, A. di Fenza, H. Gates, A. K. Gerdin, E. Golini, J. M. Hancock, W. Hans, S. M. Holter, T. Hough, P. Jurdic, T. M. Keane, H. Morgan, W. Muller, F. Neff, G. Nicholson, B. Pasche, L. A. Roberson, J. Rozman, M. Sanderson, L. Santos, M. Selloum, C. Shannon, A. Southwell, G. P. Tocchini-Valentini, V. E. Vancollie, H. Westerberg, W. Wurst, M. Zi, B. Yalcin, R. Ramirez-Solis, K. P. Steel, A. M. Mallon, M. H. de Angelis, Y. Herault, S. D. M. Brown

Research output: Contribution to journal › Article › peer-review

Abstract

Background: The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms. Results: We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems. Conclusions: Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.

Original language	English
Article number	R82
Journal	Genome Biology
Volume	14
Issue number	7
DOIs	https://doi.org/10.1186/gb-2013-14-7-r82
Publication status	Published - 2013

Keywords / Materials (for Non-textual outputs)

Mouse inbred lines sequence variation mouse phenotyping gene knockout C57BL/6 sequencing data complex traits gene-function resource mice europhenome annotation substrains variants database

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10.1186/gb-2013-14-7-r82

A comparative phenotypic and genomic analysis of C57BL 6J and C57BL 6N mouse strains
© 2013 Simon et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Final published version, 3.49 MBLicence: Creative Commons: Attribution (CC-BY)

http://genomebiology.com/2013/14/7/R82

Innate immunity and endemic diseases in livestock species
Collie, D. (Principal Investigator), Beard, P. (Co-investigator), Bishop, S. (Co-investigator), Bronsvoort, M. (Co-investigator), Burt, D. (Co-investigator), Fitzgerald, R. (Co-investigator), Freeman, T. (Co-investigator), Gally, D. (Co-investigator), Gill, A. (Co-investigator), Glass, E. (Co-investigator), Hocking, P. (Co-investigator), Hope, J. (Co-investigator), Hume, D. (Co-investigator), Kaiser, P. (Co-investigator), Mabbott, N. (Co-investigator), McLachlan, G. (Co-investigator), Morrison, L. (Co-investigator), Stevens, J. (Co-investigator), Stevens, M. (Co-investigator) & Watson, M. (Co-investigator)
BBSRC
1/04/12 → 31/03/17
Project: Research

Cite this

Simon, M. M., Greenaway, S., White, J. K., Fuchs, H., Gailus-Durner, V., Wells, S., Sorg, T., Wong, K., Bedu, E., Cartwright, E. J., Dacquin, R., Djebali, S., Estabel, J., Graw, J., Ingham, N. J., Jackson, I. J., Lengeling, A., Mandillo, S., Marvel, J., ... Brown, S. D. M. (2013). A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains. Genome Biology, 14(7), Article R82. https://doi.org/10.1186/gb-2013-14-7-r82

@article{0084fc46a1c548099b144d08fb8bffe4,

title = "A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains",

abstract = "Background: The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms. Results: We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems. Conclusions: Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.",

keywords = "Mouse inbred lines sequence variation mouse phenotyping gene knockout C57BL/6 sequencing data complex traits gene-function resource mice europhenome annotation substrains variants database",

author = "Simon, {M. M.} and S. Greenaway and White, {J. K.} and H. Fuchs and V. Gailus-Durner and S. Wells and T. Sorg and K. Wong and E. Bedu and Cartwright, {E. J.} and R. Dacquin and S. Djebali and J. Estabel and J. Graw and Ingham, {N. J.} and Jackson, {I. J.} and A. Lengeling and S. Mandillo and J. Marvel and H. Meziane and F. Preitner and O. Puk and M. Roux and Adams, {D. J.} and S. Atkins and A. Ayadi and L. Becker and A. Blake and D. Brooker and H. Cater and Champy, {M. F.} and R. Combe and P. Danecek and {di Fenza}, A. and H. Gates and Gerdin, {A. K.} and E. Golini and Hancock, {J. M.} and W. Hans and Holter, {S. M.} and T. Hough and P. Jurdic and Keane, {T. M.} and H. Morgan and W. Muller and F. Neff and G. Nicholson and B. Pasche and Roberson, {L. A.} and J. Rozman and M. Sanderson and L. Santos and M. Selloum and C. Shannon and A. Southwell and Tocchini-Valentini, {G. P.} and Vancollie, {V. E.} and H. Westerberg and W. Wurst and M. Zi and B. Yalcin and R. Ramirez-Solis and Steel, {K. P.} and Mallon, {A. M.} and {de Angelis}, {M. H.} and Y. Herault and Brown, {S. D. M.}",

year = "2013",

doi = "10.1186/gb-2013-14-7-r82",

language = "English",

volume = "14",

journal = "Genome Biology",

issn = "1465-6906",

publisher = "BioMed Central",

number = "7",

}

Simon, MM, Greenaway, S, White, JK, Fuchs, H, Gailus-Durner, V, Wells, S, Sorg, T, Wong, K, Bedu, E, Cartwright, EJ, Dacquin, R, Djebali, S, Estabel, J, Graw, J, Ingham, NJ, Jackson, IJ, Lengeling, A, Mandillo, S, Marvel, J, Meziane, H, Preitner, F, Puk, O, Roux, M, Adams, DJ, Atkins, S, Ayadi, A, Becker, L, Blake, A, Brooker, D, Cater, H, Champy, MF, Combe, R, Danecek, P, di Fenza, A, Gates, H, Gerdin, AK, Golini, E, Hancock, JM, Hans, W, Holter, SM, Hough, T, Jurdic, P, Keane, TM, Morgan, H, Muller, W, Neff, F, Nicholson, G, Pasche, B, Roberson, LA, Rozman, J, Sanderson, M, Santos, L, Selloum, M, Shannon, C, Southwell, A, Tocchini-Valentini, GP, Vancollie, VE, Westerberg, H, Wurst, W, Zi, M, Yalcin, B, Ramirez-Solis, R, Steel, KP, Mallon, AM, de Angelis, MH, Herault, Y & Brown, SDM 2013, 'A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains', Genome Biology, vol. 14, no. 7, R82. https://doi.org/10.1186/gb-2013-14-7-r82

TY - JOUR

T1 - A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains

AU - Simon, M. M.

AU - Greenaway, S.

AU - White, J. K.

AU - Fuchs, H.

AU - Gailus-Durner, V.

AU - Wells, S.

AU - Sorg, T.

AU - Wong, K.

AU - Bedu, E.

AU - Cartwright, E. J.

AU - Dacquin, R.

AU - Djebali, S.

AU - Estabel, J.

AU - Graw, J.

AU - Ingham, N. J.

AU - Jackson, I. J.

AU - Lengeling, A.

AU - Mandillo, S.

AU - Marvel, J.

AU - Meziane, H.

AU - Preitner, F.

AU - Puk, O.

AU - Roux, M.

AU - Adams, D. J.

AU - Atkins, S.

AU - Ayadi, A.

AU - Becker, L.

AU - Blake, A.

AU - Brooker, D.

AU - Cater, H.

AU - Champy, M. F.

AU - Combe, R.

AU - Danecek, P.

AU - di Fenza, A.

AU - Gates, H.

AU - Gerdin, A. K.

AU - Golini, E.

AU - Hancock, J. M.

AU - Hans, W.

AU - Holter, S. M.

AU - Hough, T.

AU - Jurdic, P.

AU - Keane, T. M.

AU - Morgan, H.

AU - Muller, W.

AU - Neff, F.

AU - Nicholson, G.

AU - Pasche, B.

AU - Roberson, L. A.

AU - Rozman, J.

AU - Sanderson, M.

AU - Santos, L.

AU - Selloum, M.

AU - Shannon, C.

AU - Southwell, A.

AU - Tocchini-Valentini, G. P.

AU - Vancollie, V. E.

AU - Westerberg, H.

AU - Wurst, W.

AU - Zi, M.

AU - Yalcin, B.

AU - Ramirez-Solis, R.

AU - Steel, K. P.

AU - Mallon, A. M.

AU - de Angelis, M. H.

AU - Herault, Y.

AU - Brown, S. D. M.

PY - 2013

Y1 - 2013

N2 - Background: The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms. Results: We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems. Conclusions: Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.

AB - Background: The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms. Results: We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems. Conclusions: Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.

KW - Mouse inbred lines sequence variation mouse phenotyping gene knockout C57BL/6 sequencing data complex traits gene-function resource mice europhenome annotation substrains variants database

U2 - 10.1186/gb-2013-14-7-r82

DO - 10.1186/gb-2013-14-7-r82

M3 - Article

C2 - 23902802

SN - 1465-6906

VL - 14

JO - Genome Biology

JF - Genome Biology

IS - 7

M1 - R82

ER -

A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains

Abstract

Keywords / Materials (for Non-textual outputs)

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Innate immunity and endemic diseases in livestock species

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