title: Haplotype tag single nucleotide polymorphism analysis of the human orthologues of the rat type 1 diabetes genes Ian4 (Lyp/Iddm1) and Cblb.
abstract: The diabetes-prone BioBreeding (BB) and Komeda diabetes-prone (KDP) rats are both spontaneous animal models of human autoimmune, T-cell-associated type 1 diabetes. Both resemble the human disease, and consequently, susceptibility genes for diabetes found in these two strains can be considered as potential candidate genes in humans. Recently, a frameshift deletion in Ian4, a member of the immune-associated nucleotide (Ian)-related gene family, has been shown to map to BB rat Iddm1. In the KDP rat, a nonsense mutation in the T-cell regulatory gene, Cblb, has been described as a major susceptibility locus. Following a strategy of examining the human orthologues of susceptibility genes identified in animal models for association with type 1 diabetes, we identified single nucleotide polymorphisms (SNPs) from each gene by resequencing PCR product from at least 32 type 1 diabetic patients. Haplotype tag SNPs (htSNPs) were selected and genotyped in 754 affected sib-pair families from the U.K. and U.S. Evaluation of disease association by a multilocus transmission/disequilibrium test (TDT) gave a P value of 0.484 for IAN4L1 and 0.692 for CBLB, suggesting that neither gene influences susceptibility to common alleles of human type 1 diabetes in these populations.
authors.affiliation: Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, U.K.
authors.forename: Felicity
authors.initials: F
authors.lastname: Payne
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Smyth
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pask
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Barratt
authors.forename: Jason D
authors.initials: JD
authors.lastname: Cooper
authors.forename: Rebecca C J
authors.initials: RC
authors.lastname: Twells
authors.forename: Neil M
authors.initials: NM
authors.lastname: Walker
authors.forename: Alex C
authors.initials: AC
authors.lastname: Lam
authors.forename: Luc J
authors.initials: LJ
authors.lastname: Smink
authors.forename: Sarah
authors.initials: S
authors.lastname: Nutland
authors.forename: Helen E
authors.initials: HE
authors.lastname: Rance
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018389:Codon, Nonsense; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005190:Family; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D050721:Proto-Oncogene Proteins c-cbl; D051381:Rats; D011913:Rats, Inbred BB; D035781:Siblings; D013045:Species Specificity; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C492213:Cblb protein, rat; D018389:Codon, Nonsense; C492211:CBLB protein, human; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases