Sawcer Stephen
University of Cambridge, Department of Clinical Neuroscience, Addenbrooke's Hospital, Cambridge, UK.
Curr Opin Neurol. 2006 Jun;19(3):237-41. doi: 10.1097/01.wco.0000227031.39834.31.
This review covers the latest developments in the genetic analysis of multiple sclerosis in the context of advancing knowledge about the nature of complex disease. This year has seen rapid progress dominated by early applications of high-throughput single-nucleotide polymorphism typing technology.
The last 12 months have seen the completion of what is probably a definitive screen for linkage, together with the beginnings of indirect full-genome screens for association with common variants. Alongside this the first ever systematic admixture mapping effort has also been completed, suggesting a possible explanation for the apparent excess of the condition in Europeans and implicating a novel susceptibility locus on chromosome 1.
It is now clear that association-based studies in large cohorts will be needed to unravel the genetic basis of susceptibility to multiple sclerosis. Importantly it is also clear that the necessary tools have now arrived and that the next few years are likely to see exciting developments.
本综述涵盖了在对复杂疾病本质的认识不断推进的背景下,多发性硬化症基因分析的最新进展。今年,高通量单核苷酸多态性分型技术的早期应用主导了快速进展。
在过去12个月里,可能是确定性连锁筛查已经完成,同时针对与常见变异体关联的间接全基因组筛查也已开始。与此同时,首次系统性的混合映射研究也已完成,这为欧洲人该疾病明显过多的现象提供了一种可能的解释,并暗示了1号染色体上一个新的易感位点。
现在很清楚,需要在大型队列中进行基于关联的研究,以阐明多发性硬化症易感性的遗传基础。重要的是,现在必要的工具已经具备,未来几年可能会有令人兴奋的进展。