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

Michelle M Simon; Simon Greenaway; Jacqueline K White; Helmut Fuchs; Valérie Gailus-Durner; Tania Sorg; Kim Wong; Elodie Bedu; Elizabeth Cartwright; Romain Dacquin; Sophia Djebali; Jeanne Estabel; Jochen Graw; Neil J Ingham; Ian J Jackson; Andreas Lengeling; Silvia Mandillo; Jacqueline Marvel; Hamid Meziane; Frédéric Preitner; Oliver Puk; Michel Roux; David J Adams; Sarah Atkins; Abdel Ayadi; Lore Becker; Andrew Blake; Debra Brooker; Heather Cater; Marie-France Champy; Roy Combe; Petr Danecek; Armida di Fenza; Hilary Gates; Anna-Karin Gerdin; Elisabetta Golini; John M Hancock; Wolfgang Hans; Sabine M Hölter; Tertius Hough; Pierre Jurdic; Thomas M Keane; Hugh Morgan; Werner Muller; Frauke Neff; George Nicholson; Bastian Pasche; Laura-Anne Roberson; Jan Rozman; Mark Sanderson; Luis Santos; Mohammed Selloum; Carl Shannon; Anne Southwell; Glauco P Tocchini-Valentini; Valerie E Vancollie; Sara Wells; Henrik Westerberg; Wolfgang Wurst; Min Zi; Binnaz Yalcin; Ramiro Ramirez-Solis; Karen P Steel; Ann-Marie Mallon; Martin Hrab 283 de Angelis; Yann Herault; Steve Dm Brown

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

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

Michelle M Simon, Simon Greenaway, Jacqueline K White, Helmut Fuchs, Valérie Gailus-Durner, Tania Sorg, Kim Wong, Elodie Bedu, Elizabeth Cartwright, Romain Dacquin, Sophia Djebali, Jeanne Estabel, Jochen Graw, Neil J Ingham, Ian J Jackson, Andreas Lengeling, Silvia Mandillo, Jacqueline Marvel, Hamid Meziane, Frédéric PreitnerOliver Puk, Michel Roux, David J Adams, Sarah Atkins, Abdel Ayadi, Lore Becker, Andrew Blake, Debra Brooker, Heather Cater, Marie-France Champy, Roy Combe, Petr Danecek, Armida di Fenza, Hilary Gates, Anna-Karin Gerdin, Elisabetta Golini, John M Hancock, Wolfgang Hans, Sabine M Hölter, Tertius Hough, Pierre Jurdic, Thomas M Keane, Hugh Morgan, Werner Muller, Frauke Neff, George Nicholson, Bastian Pasche, Laura-Anne Roberson, Jan Rozman, Mark Sanderson, Luis Santos, Mohammed Selloum, Carl Shannon, Anne Southwell, Glauco P Tocchini-Valentini, Valerie E Vancollie, Sara Wells, Henrik Westerberg, Wolfgang Wurst, Min Zi, Binnaz Yalcin, Ramiro Ramirez-Solis, Karen P Steel, Ann-Marie Mallon, Martin Hrab 283 de Angelis, Yann Herault, Steve Dm Brown

Division of Cardiovascular Sciences (L5)

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
Journal	Genome biology
Volume	14
Issue number	7
DOIs	https://doi.org/10.1186/gb-2013-14-7-r82
Publication status	Published - 31 Jul 2013

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10.1186/gb-2013-14-7-r82

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

@article{935c8882e0f34588b21470d1ae7faa05,

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.",

author = "Simon, {Michelle M} and Simon Greenaway and White, {Jacqueline K} and Helmut Fuchs and Val{\'e}rie Gailus-Durner and Tania Sorg and Kim Wong and Elodie Bedu and Elizabeth Cartwright and Romain Dacquin and Sophia Djebali and Jeanne Estabel and Jochen Graw and Ingham, {Neil J} and Jackson, {Ian J} and Andreas Lengeling and Silvia Mandillo and Jacqueline Marvel and Hamid Meziane and Fr{\'e}d{\'e}ric Preitner and Oliver Puk and Michel Roux and Adams, {David J} and Sarah Atkins and Abdel Ayadi and Lore Becker and Andrew Blake and Debra Brooker and Heather Cater and Marie-France Champy and Roy Combe and Petr Danecek and {di Fenza}, Armida and Hilary Gates and Anna-Karin Gerdin and Elisabetta Golini and Hancock, {John M} and Wolfgang Hans and H{\"o}lter, {Sabine M} and Tertius Hough and Pierre Jurdic and Keane, {Thomas M} and Hugh Morgan and Werner Muller and Frauke Neff and George Nicholson and Bastian Pasche and Laura-Anne Roberson and Jan Rozman and Mark Sanderson and Luis Santos and Mohammed Selloum and Carl Shannon and Anne Southwell and Tocchini-Valentini, {Glauco P} and Vancollie, {Valerie E} and Sara Wells and Henrik Westerberg and Wolfgang Wurst and Min Zi and Binnaz Yalcin and Ramiro Ramirez-Solis and Steel, {Karen P} and Ann-Marie Mallon and {Hrab 283 de Angelis}, Martin and Yann Herault and Brown, {Steve Dm}",

year = "2013",

month = jul,

day = "31",

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

language = "English",

volume = "14",

journal = "Genome biology",

issn = "1465-6914",

publisher = "Springer Nature",

number = "7",

}

Simon, MM, Greenaway, S, White, JK, Fuchs, H, Gailus-Durner, V, Sorg, T, Wong, K, Bedu, E, Cartwright, E, 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, M-F, Combe, R, Danecek, P, di Fenza, A, Gates, H, Gerdin, A-K, Golini, E, Hancock, JM, Hans, W, Hölter, SM, Hough, T, Jurdic, P, Keane, TM, Morgan, H, Muller, W, Neff, F, Nicholson, G, Pasche, B, Roberson, L-A, Rozman, J, Sanderson, M, Santos, L, Selloum, M, Shannon, C, Southwell, A, Tocchini-Valentini, GP, Vancollie, VE, Wells, S, Westerberg, H, Wurst, W, Zi, M, Yalcin, B, Ramirez-Solis, R, Steel, KP, Mallon, A-M, Hrab 283 de Angelis, M, Herault, Y & Brown, SD 2013, 'A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains.', Genome biology, vol. 14, no. 7. 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, Michelle M

AU - Greenaway, Simon

AU - White, Jacqueline K

AU - Fuchs, Helmut

AU - Gailus-Durner, Valérie

AU - Sorg, Tania

AU - Wong, Kim

AU - Bedu, Elodie

AU - Cartwright, Elizabeth

AU - Dacquin, Romain

AU - Djebali, Sophia

AU - Estabel, Jeanne

AU - Graw, Jochen

AU - Ingham, Neil J

AU - Jackson, Ian J

AU - Lengeling, Andreas

AU - Mandillo, Silvia

AU - Marvel, Jacqueline

AU - Meziane, Hamid

AU - Preitner, Frédéric

AU - Puk, Oliver

AU - Roux, Michel

AU - Adams, David J

AU - Atkins, Sarah

AU - Ayadi, Abdel

AU - Becker, Lore

AU - Blake, Andrew

AU - Brooker, Debra

AU - Cater, Heather

AU - Champy, Marie-France

AU - Combe, Roy

AU - Danecek, Petr

AU - di Fenza, Armida

AU - Gates, Hilary

AU - Gerdin, Anna-Karin

AU - Golini, Elisabetta

AU - Hancock, John M

AU - Hans, Wolfgang

AU - Hölter, Sabine M

AU - Hough, Tertius

AU - Jurdic, Pierre

AU - Keane, Thomas M

AU - Morgan, Hugh

AU - Muller, Werner

AU - Neff, Frauke

AU - Nicholson, George

AU - Pasche, Bastian

AU - Roberson, Laura-Anne

AU - Rozman, Jan

AU - Sanderson, Mark

AU - Santos, Luis

AU - Selloum, Mohammed

AU - Shannon, Carl

AU - Southwell, Anne

AU - Tocchini-Valentini, Glauco P

AU - Vancollie, Valerie E

AU - Wells, Sara

AU - Westerberg, Henrik

AU - Wurst, Wolfgang

AU - Zi, Min

AU - Yalcin, Binnaz

AU - Ramirez-Solis, Ramiro

AU - Steel, Karen P

AU - Mallon, Ann-Marie

AU - Hrab 283 de Angelis, Martin

AU - Herault, Yann

AU - Brown, Steve Dm

PY - 2013/7/31

Y1 - 2013/7/31

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.

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

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

M3 - Article

C2 - 23902802

SN - 1465-6914

SN - 1474-760X

VL - 14

JO - Genome biology

JF - Genome biology

IS - 7

ER -

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

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