Bennett S T, Lucassen A M, Gough S C, Powell E E, Undlien D E, Pritchard L E, Merriman M E, Kawaguchi Y, Dronsfield M J, Pociot F
Nuffield Department of Surgery, Wellcome Trust Centre for Human Genetics, University of Oxford, UK.
Nat Genet. 1995 Mar;9(3):284-92. doi: 10.1038/ng0395-284.
The IDDM2 locus encoding susceptibility to type 1 diabetes was mapped previously to a 4.1-kb region spanning the insulin gene and a minisatellite or variable number of tandem repeats (VNTR) locus on human chromosome 11p15.5. By 'cross-match' haplotype analysis and linkage disequilibrium mapping, we have mapped the mutation IDDM2 to within the VNTR itself. Other polymorphisms were systematically excluded as primary disease determinants. Transmission of IDDM2 may be influenced by parent-of-origin phenomena. Although we show that the insulin gene is expressed biallelically in the adult pancreas, we present preliminary evidence that the level of transcription in vivo is correlated with allelic variation within the VNTR. Allelic variation at VNTRs may play an important general role in human disease.
编码1型糖尿病易感性的IDDM2基因座先前被定位到人类11号染色体p15.5上跨越胰岛素基因和一个小卫星或可变串联重复序列（VNTR）基因座的4.1kb区域。通过“交叉匹配”单倍型分析和连锁不平衡定位，我们已将突变IDDM2定位到VNTR本身内部。其他多态性被系统地排除为主要疾病决定因素。IDDM2的传递可能受亲本来源现象的影响。虽然我们表明胰岛素基因在成年胰腺中双等位基因表达，但我们提供了初步证据表明体内转录水平与VNTR内的等位基因变异相关。VNTR处的等位基因变异可能在人类疾病中发挥重要的普遍作用。
