Todd J A, Mijovic C, Fletcher J, Jenkins D, Bradwell A R, Barnett A H
Nuffield Department of Surgery, John Radcliffe Hospital, Headington, Oxford, UK.
Nature. 1989 Apr 13;338(6216):587-9. doi: 10.1038/338587a0.
INSULIN-dependent (type I) diabetes mellitus (IDDM) follows an autoimmune destruction of the insulin-producing beta-cells of the pancreas. Family and population studies indicate that predisposition is probably polygenic. At least one susceptibility gene lies within the major histocompatibility complex and is closely linked to the genes encoding the class II antigens, HLA-DR and HLA-DQ (refs 3, 4). Fine mapping of susceptibility genes by linkage analysis in families is not feasible because of infrequent recombination (linkage disequilibrium) between the DR and DQ genes. Recombination events in the past, however, have occurred and generated distinct DR-DQ haplotypes, whose frequencies vary between races. DNA sequencing and oligonucleotide dot-blot analysis of class II genes from two race-specific haplotypes indicate that susceptibility to IDDM is closely linked to the DQA1 locus and suggest that both the DQB1 (ref. 7) and DQA1 genes contribute to disease predisposition.
胰岛素依赖型（I型）糖尿病（IDDM）是由胰腺中产生胰岛素的β细胞发生自身免疫性破坏所致。家族和群体研究表明，易感性可能是多基因的。至少有一个易感基因位于主要组织相容性复合体中，并且与编码II类抗原HLA-DR和HLA-DQ的基因紧密连锁（参考文献3、4）。由于DR和DQ基因之间的重组频率较低（连锁不平衡），通过家族连锁分析对易感基因进行精细定位是不可行的。然而，过去发生过重组事件并产生了不同的DR-DQ单倍型，其频率在不同种族之间有所差异。对两种种族特异性单倍型的II类基因进行DNA测序和寡核苷酸点杂交分析表明，IDDM易感性与DQA1基因座紧密连锁，并提示DQB1（参考文献7）和DQA1基因均对疾病易感性有影响。
