RGD Reference Report - A genome scan localizes five non-MHC loci controlling collagen-induced arthritis in rats. - Rat Genome Database

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A genome scan localizes five non-MHC loci controlling collagen-induced arthritis in rats.

Authors: Remmers, EF  Longman, RE  Du, Y  O'Hare, A  Cannon, GW  Griffiths, MM  Wilder, RL 
Citation: Remmers EF, etal., Nat Genet 1996 Sep;14(1):82-5
RGD ID: 61062
Pubmed: PMID:8782824   (View Abstract at PubMed)
DOI: DOI:10.1038/ng0996-82   (Journal Full-text)

Identification of specific genetic loci that contribute to susceptibility to rheumatoid arthritis (RA) in humans has been hampered by several factors, including: i) multiple interacting genetic loci contributing to susceptibility; ii) complex interactions of environmental and genetic factors; iii) genetic heterogeneity; and iv) low penetrance. We have, therefore, mapped quantitative trait loci (QTLs) that control inflammatory arthritis susceptibility and/or severity in progeny of two inbred rat strains with significantly different susceptibilities to collagen-induced arthritis (CIA), an animal model for RA. Not surprisingly, we identified a major susceptibility factor, Cia1, on chromosome 20 in the vicinity of the rat major histocompatibility complex (MHC). However, by limiting the analysis to animals with arthritis-susceptible MHC genotypes and using genome-wide QTL analytic techniques, we also found four non-MHC QTLs-Cia2, 3, 4 and 5-on chromosomes 1, 4, 7 and 10, that contributed to disease severity. In addition, a QTL on chromosome 8 was suggestive for linkage. Characterization of the genes underlying these QTLs will facilitate the identification of key biochemical pathways regulating experimental autoimmune arthritis in rats and may provide insights into RA and other human autoimmune diseases. These genes may also represent novel targets for therapy.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Cia1RatExperimental Arthritis  IDA  RGD 
Cia2RatExperimental Arthritis  IDA  RGD 
Cia3RatExperimental Arthritis  IDA  RGD 
Cia4RatExperimental Arthritis  IDA  RGD 
Cia5RatExperimental Arthritis  IDA  RGD 
Ciaa1RatExperimental Arthritis  IDA  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ciaa1Ratincreased IgG level  QTM  RGD 
Cia2Ratjoint inflammation  QTM  RGD 
Cia3Ratjoint inflammation  QTM  RGD 
Cia4Ratjoint inflammation  QTM  RGD 
Cia5Ratjoint inflammation  QTM  RGD 
Cia1Ratjoint swelling  QTM  RGD 
Cia2Ratjoint swelling  QTM  RGD 
Cia3Ratjoint swelling  QTM  RGD 
Cia5Ratjoint swelling  QTM  RGD 
Objects Annotated

QTLs
Cia1  (Collagen induced arthritis QTL 1)
Cia2  (Collagen induced arthritis QTL 2)
Cia3  (Collagen induced arthritis QTL 3)
Cia4  (Collagen induced arthritis QTL 4)
Cia5  (Collagen induced arthritis QTL 5)
Ciaa1  (CIA Autoantibody QTL 1)

Strains
DA/Bkl  (NA)
F344/NHsd  (F344/NHsd)

Objects referenced in this article
Marker D7Arb17 D7Arb17 Rattus norvegicus
Marker D1Arb36 D1Arb36 Rattus norvegicus
Marker D4Arb21 D4Arb21 Rattus norvegicus
Marker D20Arb2 D20Arb2 Rattus norvegicus
Marker D20Wox3 D20Wox3 Rattus norvegicus
Marker D7Rat44 D7Rat44 Rattus norvegicus
Marker D1Rat212 D1Rat212 Rattus norvegicus
Marker D20Rat60 D20Rat60 Rattus norvegicus
Marker D1Arb37 D1Arb37 Rattus norvegicus
Marker D10Arb22 D10Arb22 Rattus norvegicus
Marker D4Arb24 D4Arb24 Rattus norvegicus
Marker D20Arb8 D20Arb8 Rattus norvegicus
QTL Aia3 Adjuvant induced arthritis QTL 3 Rattus norvegicus
Strain BBDR/Rhw null Rattus norvegicus
Strain BN BN Rattus norvegicus
Strain DA DA Rattus norvegicus
Strain F344/NRrrc null Rattus norvegicus
Gene Gh1 growth hormone 1 Rattus norvegicus
Gene Il2rb interleukin 2 receptor subunit beta Rattus norvegicus
Gene Pdgfrb platelet derived growth factor receptor beta Rattus norvegicus
QTL Pia5 Pristane induced arthritis QTL 5 Rattus norvegicus
Gene Prkca protein kinase C, alpha Rattus norvegicus
Gene Tgfbr1 transforming growth factor, beta receptor 1 Rattus norvegicus
Gene Timp2 TIMP metallopeptidase inhibitor 2 Rattus norvegicus

Additional Information