Evidence for a novel glaucoma locus at chromosome 3p21-22
Evidence for a novel glaucoma locus at chromosome 3p21-22
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DOI：
10.1007/s00439-005-1296-x
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发表时间：
2005-07-01
期刊：
影响因子：
5.3
通讯作者：
Bureau, A
中科院分区：
文献类型：
--
作者：
Baird, PN;Foote, SJ;Bureau, A
原发性开角型青光眼（primaryopen-angleglaucoma，POAG）是世界上最主要的致盲性眼病之一.它是一组临床可变的疾病，大多数病例表现为迟发性成人型。几个染色体位点已被牵连在疾病的病因，但因果突变只被确定在一小部分青光眼。我们先前已经描述了一个大的六代塔斯马尼亚家庭与POAG表现出遗传异质性。在这个家庭中，大约三分之一的受影响的个人提出了谷氨酰胺-368- STOP（Q368 STOP）突变的myocilin基因。我们现在使用马尔可夫链蒙特卡罗（MCMC）方法来确定第二个疾病区域在这个家庭的短臂3号染色体。该疾病基因座最初定位于标记D3 S1298，随后通过额外的定位鉴定了标记D3 S1298和D3 S1289之间9 cM的最小疾病区域。该区域与任何先前描述的POAG基因座均不重叠。使用乘法相对风险模型，我们确定了该区域和受影响个体1号染色体上的肌球蛋白Q368 STOP突变之间的正相关性。这些.研究结果提供了一个新的常染色体显性青光眼基因座在3号染色体短臂上的证据。
Primary open- angle glaucoma ( POAG) is one of the leading causes of blindness in the world. It is a clinically variable group of diseases with the majority of cases presenting as the late onset adult type. Several chromosomal loci have been implicated in disease aetiology, but causal mutations have only been identified in a small proportion of glaucoma. We have previously described a large six- generation Tasmanian family with POAG exhibiting genetic heterogeneity. In this family, approximately one third of affected individuals presented with a glutamine- 368- STOP ( Q368STOP) mutation in the myocilin gene. We now use a Markov Chain Monte Carlo ( MCMC) method to identify a second disease region in this family on the short arm of chromosome 3. This disease locus was initially mapped to the marker D3S1298 and a subsequent minimum disease region of 9 cM between markers D3S1298 and D3S1289 was identified through additional mapping. The region did not overlap with any previously described locus for POAG. Using a multiplicative relative risk model, we identified a positive association between this region and the Q368STOP mutation of myocilin on chromosome 1 in affected individuals. These. findings provide evidence of a new autosomal dominant glaucoma locus on the short arm of chromosome 3.