对11号染色体上1型糖尿病基因座（IDDM4）进行精细定位，并通过患病同胞对及连锁不平衡分析评估两个候选基因（FADD和GALN）。

Fine-mapping of the type 1 diabetes locus (IDDM4) on chromosome 11q and evaluation of two candidate genes (FADD and GALN) by affected sibpair and linkage-disequilibrium analyses.

作者信息

Eckenrode S, Marron M P, Nicholls R, Yang M C, Yang J J, Guida Fonseca L C, She J X

机构信息

Department of Pathology, Immunology and Laboratory Medicine, and Center for Mammalian Genetics, College of Medicine, University of Florida, Gainesville 32610, USA.

出版信息

Hum Genet. 2000 Jan;106(1):14-8. doi: 10.1007/s004399900186.

DOI:10.1007/s004399900186

PMID:10982176

Abstract

Previous studies have identified a susceptibility region for insulin-dependent (type 1) diabetes mellitus on chromosome 11q13 (IDDM4). In this study, 15 polymorphic markers were analyzed for 382 affected sibpair (ASP) families with type 1 diabetes. Our analyses provided additional evidence for linkage for IDDM4 (a peak LOD score of 3.4 at D11S913). The markers with strong linkage evidence are located within an interval of approximately 6 cM between D11S4205 and GALN. We also identified polymorphisms in two candidate genes, Fas-associated death domain protein (FADD) and galanin (GALN). Analyses of the data by transmission/disequilibrium test (TDT) and extended TDT (ETDT) did not provide any evidence for association/linkage with these candidate genes. However, ETDT did reveal significant association/linkage with the marker D11S987 (P=0.0004) within the IDDM4 interval defined by ASP analyses, suggesting that IDDM4 may be in the close proximity of D11S987.

摘要

先前的研究已确定11号染色体q13区域（IDDM4）为胰岛素依赖型（1型）糖尿病的一个易感区域。在本研究中，对382个1型糖尿病患病同胞对（ASP）家系分析了15个多态性标记。我们的分析为IDDM4的连锁提供了更多证据（在D11S913处最高对数优势积分为3.4）。具有强连锁证据的标记位于D11S4205和甘丙肽（GALN）之间约6厘摩的区间内。我们还在两个候选基因，即Fas相关死亡结构域蛋白（FADD）和甘丙肽（GALN）中鉴定到了多态性。通过传递/不平衡检验（TDT）和扩展TDT（ETDT）对数据进行分析，未发现与这些候选基因存在关联/连锁的任何证据。然而，ETDT确实揭示了与ASP分析所定义的IDDM4区间内的标记D11S987存在显著关联/连锁（P = 0.0004），这表明IDDM4可能与D11S987紧邻。