{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T07:06:00Z","timestamp":1782025560146,"version":"3.54.5"},"reference-count":48,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"content-version":"vor","delay-in-days":4561,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,4,1]]},"abstract":"<jats:sec><jats:title>OBJECTIVE<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESEARCH DESIGN AND METHODS<\/jats:title><jats:p>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\u2013resistant, double congenic ACI.BBDP-RT1u,Gimap5 (ACI.BB1u.lyp) rats, where both Iddm1 and Iddm2 were fixed as BBDP.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>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\u2013unlinked 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.2337\/db08-1215","type":"journal-article","created":{"date-parts":[[2009,1,24]],"date-time":"2009-01-24T01:46:28Z","timestamp":1232761588000},"page":"1007-1017","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":69,"title":["Type 1 Diabetes in the BB Rat: A Polygenic Disease"],"prefix":"10.2337","volume":"58","author":[{"given":"Robert H.","family":"Wallis","sequence":"first","affiliation":[{"name":"Sunnybrook Health Sciences Centre Research Institute, Departments of Medicine and Immunology, University of Toronto, Toronto, Ontario, Canada; the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KeSheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada; the"},{"name":"Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, Tennessee; the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leili","family":"Marandi","sequence":"additional","affiliation":[{"name":"Sunnybrook Health Sciences Centre Research Institute, Departments of Medicine and Immunology, University of Toronto, Toronto, Ontario, Canada; the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Sunnybrook Health Sciences Centre Research Institute, Departments of Medicine and Immunology, University of Toronto, Toronto, Ontario, Canada; the"},{"name":"Department of Laboratory Medicine and Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; 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