Combined sequence-based and genetic mapping analysis of complex traits in outbred rats

A. Baud; R. Hermsen; V. Guryev; P. Stridh; D. Graham; M.W. McBride; T. Foroud; S. Calderari; M. Diez; J. Ockinger; A.D. Beyeen; A. Gillett; N. Abdelmagid; A.O. Guerreiro-Cacais; M. Jagodic; J. Tuncel; U. Norin; E. Beattie; N. Huynh; W.H. Miller; D.L. Koller; I. Alam; S. Falak; M. Osborne-Pellegrin; E. Martinez-Membrives; T. Canete; G. Blazquez; E. Vicens-Costa; C. Mont-Cardona; S. Diaz-Moran; A. Tobena; O. Hummel; D. Zelenika; K. Saar; G. Patone; A. Bauerfeind; M.T. Bihoreau; M. Heinig; Y.A. Lee; C. Rintisch; H. Schulz; D.A. Wheeler; K.C. Worley; D.M. Muzny; R.A. Gibbs; M. Lathrop; N. Lansu; P. Toonen; F.P. Ruzius; E. de Bruijn; H. Hauser; D.J. Adams; T. Keane; S.S. Atanur; T.J. Aitman; P. Flicek; T. Malinauskas; E.Y. Jones; D. Ekman; R. Lopez-Aumatell; A.F. Dominiczak; M. Johannesson; R. Holmdahl; T. Olsson; D. Gauguier; N. Hubner; A. Fernandez-Teruel; E. Cuppen; R. Mott; J. Flint

doi:10.1038/ng.2644

Combined sequence-based and genetic mapping analysis of complex traits in outbred rats

A. Baud, R. Hermsen, V. Guryev, P. Stridh, D. Graham, M.W. McBride, T. Foroud, S. Calderari, M. Diez, J. Ockinger, A.D. Beyeen, A. Gillett, N. Abdelmagid, A.O. Guerreiro-Cacais, M. Jagodic, J. Tuncel, U. Norin, E. Beattie, N. Huynh, W.H. MillerD.L. Koller, I. Alam, S. Falak, M. Osborne-Pellegrin, E. Martinez-Membrives, T. Canete, G. Blazquez, E. Vicens-Costa, C. Mont-Cardona, S. Diaz-Moran, A. Tobena, O. Hummel, D. Zelenika, K. Saar, G. Patone, A. Bauerfeind, M.T. Bihoreau, M. Heinig, Y.A. Lee, C. Rintisch, H. Schulz, D.A. Wheeler, K.C. Worley, D.M. Muzny, R.A. Gibbs, M. Lathrop, N. Lansu, P. Toonen, F.P. Ruzius, E. de Bruijn, H. Hauser, D.J. Adams, T. Keane, S.S. Atanur, T.J. Aitman, P. Flicek, T. Malinauskas, E.Y. Jones, D. Ekman, R. Lopez-Aumatell, A.F. Dominiczak, M. Johannesson, R. Holmdahl, T. Olsson, D. Gauguier, N. Hubner, A. Fernandez-Teruel, E. Cuppen, R. Mott, J. Flint

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

131 Citations (Scopus)

Abstract

Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species.

Original language	English
Pages (from-to)	767-775
Journal	Nature Genetics
Volume	45
Issue number	7
DOIs	https://doi.org/10.1038/ng.2644
Publication status	Published - 2013

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Baud, A., Hermsen, R., Guryev, V., Stridh, P., Graham, D., McBride, M. W., Foroud, T., Calderari, S., Diez, M., Ockinger, J., Beyeen, A. D., Gillett, A., Abdelmagid, N., Guerreiro-Cacais, A. O., Jagodic, M., Tuncel, J., Norin, U., Beattie, E., Huynh, N., ... Flint, J. (2013). Combined sequence-based and genetic mapping analysis of complex traits in outbred rats. Nature Genetics, 45(7), 767-775. https://doi.org/10.1038/ng.2644

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title = "Combined sequence-based and genetic mapping analysis of complex traits in outbred rats",

abstract = "Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species.",

author = "A. Baud and R. Hermsen and V. Guryev and P. Stridh and D. Graham and M.W. McBride and T. Foroud and S. Calderari and M. Diez and J. Ockinger and A.D. Beyeen and A. Gillett and N. Abdelmagid and A.O. Guerreiro-Cacais and M. Jagodic and J. Tuncel and U. Norin and E. Beattie and N. Huynh and W.H. Miller and D.L. Koller and I. Alam and S. Falak and M. Osborne-Pellegrin and E. Martinez-Membrives and T. Canete and G. Blazquez and E. Vicens-Costa and C. Mont-Cardona and S. Diaz-Moran and A. Tobena and O. Hummel and D. Zelenika and K. Saar and G. Patone and A. Bauerfeind and M.T. Bihoreau and M. Heinig and Y.A. Lee and C. Rintisch and H. Schulz and D.A. Wheeler and K.C. Worley and D.M. Muzny and R.A. Gibbs and M. Lathrop and N. Lansu and P. Toonen and F.P. Ruzius and {de Bruijn}, E. and H. Hauser and D.J. Adams and T. Keane and S.S. Atanur and T.J. Aitman and P. Flicek and T. Malinauskas and E.Y. Jones and D. Ekman and R. Lopez-Aumatell and A.F. Dominiczak and M. Johannesson and R. Holmdahl and T. Olsson and D. Gauguier and N. Hubner and A. Fernandez-Teruel and E. Cuppen and R. Mott and J. Flint",

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doi = "10.1038/ng.2644",

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journal = "Nature Genetics",

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Baud, A, Hermsen, R, Guryev, V, Stridh, P, Graham, D, McBride, MW, Foroud, T, Calderari, S, Diez, M, Ockinger, J, Beyeen, AD, Gillett, A, Abdelmagid, N, Guerreiro-Cacais, AO, Jagodic, M, Tuncel, J, Norin, U, Beattie, E, Huynh, N, Miller, WH, Koller, DL, Alam, I, Falak, S, Osborne-Pellegrin, M, Martinez-Membrives, E, Canete, T, Blazquez, G, Vicens-Costa, E, Mont-Cardona, C, Diaz-Moran, S, Tobena, A, Hummel, O, Zelenika, D, Saar, K, Patone, G, Bauerfeind, A, Bihoreau, MT, Heinig, M, Lee, YA, Rintisch, C, Schulz, H, Wheeler, DA, Worley, KC, Muzny, DM, Gibbs, RA, Lathrop, M, Lansu, N, Toonen, P, Ruzius, FP, de Bruijn, E, Hauser, H, Adams, DJ, Keane, T, Atanur, SS, Aitman, TJ, Flicek, P, Malinauskas, T, Jones, EY, Ekman, D, Lopez-Aumatell, R, Dominiczak, AF, Johannesson, M, Holmdahl, R, Olsson, T, Gauguier, D, Hubner, N, Fernandez-Teruel, A, Cuppen, E, Mott, R & Flint, J 2013, 'Combined sequence-based and genetic mapping analysis of complex traits in outbred rats', Nature Genetics, vol. 45, no. 7, pp. 767-775. https://doi.org/10.1038/ng.2644

TY - JOUR

T1 - Combined sequence-based and genetic mapping analysis of complex traits in outbred rats

AU - Baud, A.

AU - Hermsen, R.

AU - Guryev, V.

AU - Stridh, P.

AU - Graham, D.

AU - McBride, M.W.

AU - Foroud, T.

AU - Calderari, S.

AU - Diez, M.

AU - Ockinger, J.

AU - Beyeen, A.D.

AU - Gillett, A.

AU - Abdelmagid, N.

AU - Guerreiro-Cacais, A.O.

AU - Jagodic, M.

AU - Tuncel, J.

AU - Norin, U.

AU - Beattie, E.

AU - Huynh, N.

AU - Miller, W.H.

AU - Koller, D.L.

AU - Alam, I.

AU - Falak, S.

AU - Osborne-Pellegrin, M.

AU - Martinez-Membrives, E.

AU - Canete, T.

AU - Blazquez, G.

AU - Vicens-Costa, E.

AU - Mont-Cardona, C.

AU - Diaz-Moran, S.

AU - Tobena, A.

AU - Hummel, O.

AU - Zelenika, D.

AU - Saar, K.

AU - Patone, G.

AU - Bauerfeind, A.

AU - Bihoreau, M.T.

AU - Heinig, M.

AU - Lee, Y.A.

AU - Rintisch, C.

AU - Schulz, H.

AU - Wheeler, D.A.

AU - Worley, K.C.

AU - Muzny, D.M.

AU - Gibbs, R.A.

AU - Lathrop, M.

AU - Lansu, N.

AU - Toonen, P.

AU - Ruzius, F.P.

AU - de Bruijn, E.

AU - Hauser, H.

AU - Adams, D.J.

AU - Keane, T.

AU - Atanur, S.S.

AU - Aitman, T.J.

AU - Flicek, P.

AU - Malinauskas, T.

AU - Jones, E.Y.

AU - Ekman, D.

AU - Lopez-Aumatell, R.

AU - Dominiczak, A.F.

AU - Johannesson, M.

AU - Holmdahl, R.

AU - Olsson, T.

AU - Gauguier, D.

AU - Hubner, N.

AU - Fernandez-Teruel, A.

AU - Cuppen, E.

AU - Mott, R.

AU - Flint, J.

N1 - Reporting year: 2013

PY - 2013

Y1 - 2013

N2 - Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species.

AB - Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species.

U2 - 10.1038/ng.2644

DO - 10.1038/ng.2644

M3 - Article

SN - 1061-4036

VL - 45

SP - 767

EP - 775

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -

Combined sequence-based and genetic mapping analysis of complex traits in outbred rats

Abstract

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