DESCRIPTION:

QTL Associated with Glucose Level. On Chromosome 8 with a LOD score= 4.72, p-value =0.001. From a(n) of

LABEL:

QTL-Iddm24-Rat-Chr 8

SCORE TYPE:

Binary

DATE ADDED:

2015-06-10

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Wallis RH, Wang K, Dabrowski D, Marandi L, Ning T, Hsieh E, Paterson AD, Mordes JP, Blankenhorn EP, Poussier P

TITLE:

A novel susceptibility locus on rat chromosome 8 affects spontaneous but not experimentally induced type 1 diabetes.

JOURNAL:

Diabetes None None, Vol 56, pp. 1731-6

ABSTRACT:

1. Diabetes. 2007 Jun;56(6):1731-6. Epub 2007 Mar 27. A novel susceptibility locus on rat chromosome 8 affects spontaneous but not experimentally induced type 1 diabetes. Wallis RH(1), Wang K, Dabrowski D, Marandi L, Ning T, Hsieh E, Paterson AD, Mordes JP, Blankenhorn EP, Poussier P. Author information: (1)Department of Medicine, Sunnybrook and Women's College Health Sciences Centre Research Institute, University of Toronto, Toronto, Ontario, Canada. OBJECTIVE: The biobreeding diabetes-prone (BBDP) rat spontaneously develops type 1 diabetes. Two of the genetic factors contributing to this syndrome are the major histocompatibility complex (Iddm1) and a Gimap5 mutation (Iddm2) responsible for a T-lymphopenia. Susceptibility to experimentally induced type 1 diabetes is widespread among nonlymphopenic (wild-type Iddm2) rat strains provided they share the BBDP Iddm1 allele. The question follows as to whether spontaneous and experimentally induced type 1 diabetes share susceptibility loci besides Iddm1. Our objectives were to map a novel, serendipitously discovered Iddm locus, confirm its effects by developing congenic sublines, and assess its differential contribution to spontaneous and experimentally induced type 1 diabetes. RESEARCH DESIGN AND METHODS: An unexpected reduction in spontaneous type 1 diabetes incidence (86 to 31%, P < 0.0001) was observed in a BBDP line congenic for a Wistar Furth-derived allotypic marker, RT7 (chromosome 13). Genome-wide analysis revealed that, besides the RT7 locus, a Wistar Furth chromosome 8 fragment had also been introduced. The contribution of these intervals to diabetes resistance was assessed through linkage analysis using 134 F2 (BBDP x double congenic line) animals and a panel of congenic sublines. One of these sublines, resistant to spontaneous type 1 diabetes, was tested for susceptibility to experimentally induced type 1 diabetes. RESULTS: Both linkage analysis and congenic sublines mapped a novel locus (Iddm24) to the telomeric 10.34 Mb of chromosome 8, influencing cumulative incidence and age of onset of spontaneous type 1 diabetes but not insulitis nor experimentally induced type 1 diabetes. CONCLUSIONS: This study has identified a type 1 diabetes susceptibility locus that appears to act after the development of insulitis and that regulates spontaneous type 1 diabetes exclusively. PMCID: PMC3987115 PMID: 17389329 [PubMed - indexed for MEDLINE] PUBMED: 17389329
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