DESCRIPTION:

QTL Associated with Glucose level. On Chromosome 14 with a LOD score= 4.08, p-value =. From a(n) intercross of

LABEL:

QTL-Iddm31-Rat-Chr 14

SCORE TYPE:

Binary

DATE ADDED:

2015-06-10

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Wallis RH, Wang K, Marandi L, Hsieh E, Ning T, Chao GY, Sarmiento J, Paterson AD, Poussier P

TITLE:

Type 1 diabetes in the BB rat: a polygenic disease.

JOURNAL:

Diabetes None None, Vol 58, pp. 1007-17

ABSTRACT:

1. Diabetes. 2009 Apr;58(4):1007-17. doi: 10.2337/db08-1215. Epub 2009 Jan 23. Type 1 diabetes in the BB rat: a polygenic disease. Wallis RH(1), Wang K, Marandi L, Hsieh E, Ning T, Chao GY, Sarmiento J, Paterson AD, Poussier P. Author information: (1)Sunnybrook Health Sciences Centre Research Institute, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Comment in Diabetes. 2009 Apr;58(4):796-7. OBJECTIVE: Two type 1 diabetes susceptibility genes have been identified in the spontaneously diabetic biobreeding diabetes-prone (BBDP) rat, the major histocompatibility complex (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 type 1 diabetes is a polygenic disease in the BBDP rat. RESEARCH DESIGN AND METHODS: We performed the most comprehensive genome-wide linkage analysis for type 1 diabetes, age of disease onset (AOO), and insulitis subphenotypes in 574 F2 animals from a cross-intercross between BBDP and type 1 diabetes-resistant, double congenic ACI.BBDP-RT1u,Gimap5 (ACI.BB(1u.lyp)) rats, where both Iddm1 and Iddm2 were fixed as BBDP. RESULTS: A total of 19% of these F2 animals developed type 1 diabetes, and eight type 1 diabetes 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 type 1 diabetes-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 type 1 diabetes. INS, PTPN22, IL2/IL21, C1QTNF6, and C12orf30, associated with human type 1 diabetes, 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 besides MHC class II with human type 1 diabetes. PMCID: PMC2661594 PMID: 19168599 [PubMed - indexed for MEDLINE] PUBMED: 19168599
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