RGD Reference Report - TYPE 1 DIABETES IN THE BB RAT: A POLYGENIC DISEASE. - Rat Genome Database

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Authors: Wallis, RH  Wang, K  Marandi, L  Hsieh, E  Ning, T  Chao, GY  Sarmiento, J  Paterson, AD  Poussier, P 
Citation: Wallis RH, etal., Diabetes. 2009 Apr;58(4):1007-17. Epub 2009 Jan 23
RGD ID: 2303106
Pubmed: PMID:19168599   (View Abstract at PubMed)
PMCID: PMC2661594   (View Article at PubMed Central)
DOI: DOI:10.2337/db08-1215   (Journal Full-text)

Objective: Two type 1 diabetes (T1D) susceptibility genes have been identified in the spontaneously diabetic BBDP rat, the MHC (RT1) Class II u haplotype (Iddm1), and Gimap5 (Iddm2). The strong effects of these have impeded previous efforts to map additional loci. We tested the hypothesis that T1D is a polygenic disease in the BBDP rat. Research Design and Methods: We performed the most comprehensive genome-wide linkage analysis for T1D, age of disease onset (AOO), and insulitis sub-phenotypes in 574 F2 animals from a cross-intercross between BBDP and T1D-resistant, double congenic ACI.BBDP-RT1u,GIMAP5 (ACI.BB(1u.lyp)) rats, where both Iddm1 and Iddm2 were fixed as BBDP. Results: Nineteen percent of these F2 animals developed T1D, and eight T1D susceptibility loci were mapped, six showing significant linkage (chromosomes 1, 3, 6(two loci), 12, and 14) and two (chromosomes 2 and 17), suggestive linkage. The chromosomes 6, 12, and 14 intervals were also linked to the severity of islet infiltration by immunocytes, while those on chromosomes 1, 6(two loci), 14, 17, and a T1D-unlinked chromosome 8 interval showed significant linkage to the degree of islet atrophy. Four loci exhibited suggestive linkage to AOO on chromosomes 2(two loci), 7 and 18 but were unlinked to T1D. INS, PTPN22, IL2/IL21, C1QTNF6 and C12orf30 associated with human T1D, are contained within the chromosomes 1, 2, 7 and 12 loci. Conclusions: This study demonstrates that the BBDP diabetic syndrome is a complex, polygenic disease that may share additional susceptibility genes beside MHC Class II, with human T1D.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ACI.BBDP-(RT1u)(Gimap5)/SunnRattype 1 diabetes mellitus MODEL: controlIAGP compared to BBDP/WorSunnRGD 
BBDP/WorSunnRattype 1 diabetes mellitus MODEL: spontaneousIAGP compared to ACI and ACI.BBDP-(RT1u)(Gimap5)/SunnRGD 
Iddm25Rattype 1 diabetes mellitus resistanceIDA Due to BBDP alleleRGD 
Iddm26Rattype 1 diabetes mellitus susceptibilityIDA  RGD 
Iddm27Rattype 1 diabetes mellitus resistanceIDA  RGD 
Iddm28Rattype 1 diabetes mellitus susceptibilityIDA  RGD 
Iddm29Rattype 1 diabetes mellitus susceptibilityIDA  RGD 
Iddm30Rattype 1 diabetes mellitus resistanceIDA  RGD 
Iddm31Rattype 1 diabetes mellitus susceptibilityIDA  RGD 
Iddm32Rattype 1 diabetes mellitus  IDA  RGD 
Iddm33Rattype 1 diabetes mellitus  IDA  RGD 
Iddm34Rattype 1 diabetes mellitus  IDA  RGD 
Iddm35Rattype 1 diabetes mellitus  IDA  RGD 
Iddm36Rattype 1 diabetes mellitus susceptibilityIDA  RGD 

Objects Annotated

Iddm25  (Insulin dependent diabetes mellitus QTL 25)
Iddm26  (Insulin dependent diabetes mellitus QTL 26)
Iddm27  (Insulin dependent diabetes mellitus QTL 27)
Iddm28  (Insulin dependent diabetes mellitus QTL 28)
Iddm29  (Insulin dependent diabetes mellitus QTL 29)
Iddm30  (Insulin dependent diabetes mellitus QTL 30)
Iddm31  (Insulin dependent diabetes mellitus QTL 31)
Iddm32  (Insulin dependent diabetes mellitus QTL 32)
Iddm33  (Insulin dependent diabetes mellitus QTL 33)
Iddm34  (Insulin dependent diabetes mellitus QTL 34)
Iddm35  (Insulin dependent diabetes mellitus QTL 35)
Iddm36  (Insulin dependent diabetes mellitus QTL 36)

Objects referenced in this article
QTL Iddm10 Insulin dependent diabetes mellitus QTL 10 Rattus norvegicus
QTL Iddm3 Insulin dependent diabetes mellitus QTL 3 Rattus norvegicus
QTL Iddm8 Insulin dependent diabetes mellitus QTL 8 Rattus norvegicus
QTL Iddm9 Insulin dependent diabetes mellitus QTL 9 Rattus norvegicus

Additional Information