Advanced

Primer: comparative genetics of animal models of arthritis--a tool to resolve complexity.

Holmdahl, Rikard LU (2007) In Nature Clinical Practice Rheumatology 3(2). p.104-111
Abstract
Complex traits, including inflammatory rheumatic diseases, have important genetic features, but most of the responsible genes have not been conclusively identified. Genetic analysis of inbred animal models and comparative genetics - the comparison of genes between different species - might help to identify the crucial genes and to investigate more directly the biology involved. Genome-wide linkage analysis of particular genes can be assessed by genetic segregation studies, whereas disease pathways can be delineated by the use of congenic strains. To clone disease genes, the traits need to be transformed so that they are inherited in a more Mendelian manner: achieving this pattern requires isolation of the locus on a genetic background that... (More)
Complex traits, including inflammatory rheumatic diseases, have important genetic features, but most of the responsible genes have not been conclusively identified. Genetic analysis of inbred animal models and comparative genetics - the comparison of genes between different species - might help to identify the crucial genes and to investigate more directly the biology involved. Genome-wide linkage analysis of particular genes can be assessed by genetic segregation studies, whereas disease pathways can be delineated by the use of congenic strains. To clone disease genes, the traits need to be transformed so that they are inherited in a more Mendelian manner: achieving this pattern requires isolation of the locus on a genetic background that allows high penetrance by minimization of the size of congenic fragments, genetic manipulations without associated artifacts, or identification of highly penetrant mutations by phenotypic selection. Although almost one hundred quantitative trait loci for arthritis have been identified, only a few genes have so far been positionally cloned. In this Review we highlight the possibilities of using animal models to identify genes associated with complex diseases like arthritis, illustrated with available findings for genes such as those encoding major histocompatibility complex class II, neutrophil cytosolic factor 1 (Ncf1/p47(phox)) and ZAP70. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
disease, polygenic, autoimmunity, experimental animal models, major histocompatibility complex, linkage analysis
in
Nature Clinical Practice Rheumatology
volume
3
issue
2
pages
104 - 111
publisher
Nature Publishing Group
external identifiers
  • wos:000243966500011
  • scopus:33847077246
ISSN
1745-8382
DOI
10.1038/ncprheum0400
language
English
LU publication?
yes
id
1ed05dd4-3b74-465e-baab-aaa5cbd3cacb (old id 165723)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17299448&dopt=Abstract
date added to LUP
2007-07-30 16:18:46
date last changed
2017-01-01 04:34:59
@article{1ed05dd4-3b74-465e-baab-aaa5cbd3cacb,
  abstract     = {Complex traits, including inflammatory rheumatic diseases, have important genetic features, but most of the responsible genes have not been conclusively identified. Genetic analysis of inbred animal models and comparative genetics - the comparison of genes between different species - might help to identify the crucial genes and to investigate more directly the biology involved. Genome-wide linkage analysis of particular genes can be assessed by genetic segregation studies, whereas disease pathways can be delineated by the use of congenic strains. To clone disease genes, the traits need to be transformed so that they are inherited in a more Mendelian manner: achieving this pattern requires isolation of the locus on a genetic background that allows high penetrance by minimization of the size of congenic fragments, genetic manipulations without associated artifacts, or identification of highly penetrant mutations by phenotypic selection. Although almost one hundred quantitative trait loci for arthritis have been identified, only a few genes have so far been positionally cloned. In this Review we highlight the possibilities of using animal models to identify genes associated with complex diseases like arthritis, illustrated with available findings for genes such as those encoding major histocompatibility complex class II, neutrophil cytosolic factor 1 (Ncf1/p47(phox)) and ZAP70.},
  author       = {Holmdahl, Rikard},
  issn         = {1745-8382},
  keyword      = {disease,polygenic,autoimmunity,experimental animal models,major histocompatibility complex,linkage analysis},
  language     = {eng},
  number       = {2},
  pages        = {104--111},
  publisher    = {Nature Publishing Group},
  series       = {Nature Clinical Practice Rheumatology},
  title        = {Primer: comparative genetics of animal models of arthritis--a tool to resolve complexity.},
  url          = {http://dx.doi.org/10.1038/ncprheum0400},
  volume       = {3},
  year         = {2007},
}