Linkage and association studies in insulin-dependent diabetes with a new dinucleotide repeat polymorphism at the GAD65 locus.
Linkage and association studies in insulin-dependent diabetes with a new dinucleotide repeat polymorphism at the GAD65 locus.
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DOI：
10.3109/08916939508993360
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发表时间：
1995
期刊：
影响因子：
3.5
通讯作者：
B. Wapelhorst;G. Bell;N. Risch;R. Spielman;P. Concannon
中科院分区：
文献类型：
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作者：
B. Wapelhorst;G. Bell;N. Risch;R. Spielman;P. Concannon
谷氨酸脱羧酶(GAD)是胰岛素依赖型糖尿病(IDDM)的重要自身抗原。胰岛细胞特异的65 kDa形式的GAD(GAD65)由染色体10p上的一个基因编码。最近，基于匿名标记D10S193的等位基因共享，一个可能的IDDM易感基因被定位到相同的通用区域。为了确定GAD65基因的变异是否在IDDM的遗传易感性中起作用，可能解释已报道的10P上连锁的证据，我们分离了含有GAD65的粘粒克隆，并鉴定了与该基因物理上连锁的高度多态的二核苷酸重复。利用该GAD65微卫星标记与其他10p标记D10S193和D10S211，对186个有2个或2个以上受累兄弟姐妹的多基因IDDM家系成员进行了基因分型。连锁分析将GAD65标记定位于D10S193的5.6 cM处。确定每个标记在受影响的同胞对中相同的等位基因(IBD)的共享情况，并在没有连锁的假设下与预期的50：50分布进行比较。在对数据进行分层后也进行了分析，以共享HLAII类等位基因。使用传递/不平衡检验进一步评估GAD65的家系数据与IDDM的等位基因关联。在这些测试中，没有观察到明显偏离预期值的情况，这表明GAD65基因的变异在IDDM的遗传易感性中不起重要作用。
Glutamic acid decarboxylase (GAD) is an important autoantigen in insulin-dependent diabetes mellitus (IDDM). The islet cell specific, 65 kDa form of GAD (GAD65) is encoded by a gene on chromosome 10p. Recently, a putative IDDM susceptibility gene has been localized to the same general region based on allele sharing for the anonymous marker D10S193. To determine whether variation in the GAD65 gene plays a role in genetic susceptibility to IDDM, possibly explaining the reported evidence for linkage on 10p, we isolated cosmid clones containing GAD65, and identified a highly polymorphic dinucleotide repeat physically linked to the gene. This GAD65 microsatellite marker, along with the other 10p markers D10S193 and D10S211, were used to genotype the members of 186 multiplex IDDM families with 2 or more affected siblings. Linkage analysis localized the GAD65 marker 5.6 cM from D10S193. Sharing of alleles identical by descent (IBD) in affected sib pairs for each of the markers was determined and compared to the expected 50:50 distribution under an assumption of no linkage. Analyses were also carried out after stratification of the data for sharing of HLA class.II alleles. The family data for GAD65 were further assessed for allelic association with IDDM using the transmission/disequilibrium test. No significant deviations from expected values were observed in any of these tests, suggesting that variation in the GAD65 gene does not play a significant role in genetic susceptibility to IDDM.