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High-resolution mapping of a complex disease, a model for rheumatoid arthritis, using heterogeneous stock mice

Ahlqvist, Emma LU ; Ekman, Diana; Lindvall, Therese LU ; Popovic, Marjan LU ; Förster, Michael LU ; Hultqvist, Malin LU ; Klaczkowska, Dorota; Teneva, Ivanka LU ; Johannesson, Martina LU and Flint, Jonathan, et al. (2011) In Human Molecular Genetics 20(15). p.3031-3041
Abstract
Resolving the genetic basis of complex diseases like rheumatoid arthritis will require knowledge of the corresponding diseases in experimental animals to enable translational functional studies. Mapping of quantitative trait loci in mouse models of arthritis, such as collagen-induced arthritis (CIA), using F-2 crosses has been successful, but can resolve loci only to large chromosomal regions. Using an inbred-outbred cross design, we identified and fine-mapped CIA loci on a genome-wide scale. Heterogeneous stock mice were first intercrossed with an inbred strain, B10.Q, to introduce an arthritis permitting MHCII haplotype. Homozygous H2(q) mice were then selected to set up an F-3 generation with fixed major histocompatibility complex that... (More)
Resolving the genetic basis of complex diseases like rheumatoid arthritis will require knowledge of the corresponding diseases in experimental animals to enable translational functional studies. Mapping of quantitative trait loci in mouse models of arthritis, such as collagen-induced arthritis (CIA), using F-2 crosses has been successful, but can resolve loci only to large chromosomal regions. Using an inbred-outbred cross design, we identified and fine-mapped CIA loci on a genome-wide scale. Heterogeneous stock mice were first intercrossed with an inbred strain, B10.Q, to introduce an arthritis permitting MHCII haplotype. Homozygous H2(q) mice were then selected to set up an F-3 generation with fixed major histocompatibility complex that was used for arthritis experiments. We identified 26 loci, 18 of which are novel, controlling arthritis traits such as incidence of disease, severity and time of onset and fine-mapped a number of previously mapped loci. (Less)
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publication status
published
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Human Molecular Genetics
volume
20
issue
15
pages
3031 - 3041
publisher
Oxford University Press
external identifiers
  • wos:000292560000012
  • scopus:79960129392
ISSN
0964-6906
DOI
10.1093/hmg/ddr206
language
English
LU publication?
yes
id
4e5a29a1-484f-4902-b1e9-271eecf29dda (old id 2094174)
date added to LUP
2011-09-02 08:37:37
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2017-01-01 04:03:34
@article{4e5a29a1-484f-4902-b1e9-271eecf29dda,
  abstract     = {Resolving the genetic basis of complex diseases like rheumatoid arthritis will require knowledge of the corresponding diseases in experimental animals to enable translational functional studies. Mapping of quantitative trait loci in mouse models of arthritis, such as collagen-induced arthritis (CIA), using F-2 crosses has been successful, but can resolve loci only to large chromosomal regions. Using an inbred-outbred cross design, we identified and fine-mapped CIA loci on a genome-wide scale. Heterogeneous stock mice were first intercrossed with an inbred strain, B10.Q, to introduce an arthritis permitting MHCII haplotype. Homozygous H2(q) mice were then selected to set up an F-3 generation with fixed major histocompatibility complex that was used for arthritis experiments. We identified 26 loci, 18 of which are novel, controlling arthritis traits such as incidence of disease, severity and time of onset and fine-mapped a number of previously mapped loci.},
  author       = {Ahlqvist, Emma and Ekman, Diana and Lindvall, Therese and Popovic, Marjan and Förster, Michael and Hultqvist, Malin and Klaczkowska, Dorota and Teneva, Ivanka and Johannesson, Martina and Flint, Jonathan and Valdar, William and Kutty Selva, Nandakumar and Holmdahl, Rikard},
  issn         = {0964-6906},
  language     = {eng},
  number       = {15},
  pages        = {3031--3041},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {High-resolution mapping of a complex disease, a model for rheumatoid arthritis, using heterogeneous stock mice},
  url          = {http://dx.doi.org/10.1093/hmg/ddr206},
  volume       = {20},
  year         = {2011},
}