Genomic imprinting and instability in IDDM

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Association studies in Caucasian in Caucasian populations have revealed that excess of compound DQB1^<**>0302/^<**>0201 in type 1 diabetes, orIDDM,is consistently observed compared to the ratio in Hardy-Weinberg's equilibrium. This genetic complixity strongly suggests that epigenetic and postzygotic events could be involved in the pathogenesis of this multifactorial disorder.In order to elucidate of genomic imprinting might be involved at IDDM1, in this project, test for ^<**>transmission linkage disequilibrium (TDT) of haplotypes according to the parent-of-origin among twenty-seven informative families of the autoimmune-mediated type 1 diabetic offspring were performed. We found that the highly susceptible allele DQA1^<**>0301-DQB1^<**>0302 is associated with autoimmune-mediated type 1 diabetes also in Japanese population in stead of ethnic variations of haplotypes. We also found that the susceptible allele would be preferentially transmitted from mothers but not from fathers to the a … More ffected offspring. This finding supports the hypothesis that the IDDM1 is involved in the pathogenesis of type 1 diabetes by an epigenetic mechanism.We next attempted to isolate genes that are expressed in B cells of pancreatic islets differentially between IDDM and healthy controls. For this purpose, we extracted total cellular RNA from human inslinoma and its surrounding pancreatic tissues from the same individuals. Insulin cDNA could be amplified from the RNA samples by RT-PCR using its specific primers as a control. We then reverse-transcribed the RNA with 3'anchor primer, and performed RT-PCR by 3'anchor primer and labeled 5'arbitrary primer. The patterns of identified bands in electrophoresis investigated several ESTs that expressed in the pancreatic B cells and could be detected what ESTs were B-cell specific when compared to that of normal pancreatic tissue. These results should represent an important database for the identification of differential expression of genes in B cells in according to the pathogenesis of IDDM. Less