Functional MAPT haplotypes: bridging the gap between genotype and neuropathology.
Functional MAPT haplotypes: bridging the gap between genotype and neuropathology.
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DOI：
10.1016/j.nbd.2007.04.006
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发表时间：
2007-07
影响因子：
6.1
通讯作者：
Wade-Martins, Richard
中科院分区：
文献类型：
--
作者：
Caffrey, Tara M.;Wade-Martins, Richard
关键词：
微管相关蛋白tau（MAPT）基因座长期以来与散发性神经退行性疾病相关，特别是进行性核上性麻痹和皮质基底节变性，最近与阿尔茨海默病和帕金森病相关。然而，基因关联背后的功能生物学机制现在才开始出现。跨越MAPT的区域中的基因组结构是高度复杂的，并且包括约1.8Mb的连锁不平衡（LD）块。该区域分为两个主要的单倍型，H1和H2，由许多单核苷酸多态性和抑制重组的900 kb倒位定义。MAPT区域的精细定位已经鉴定出MAPT H1单倍型的亚分支，其与神经退行性疾病特异性相关。在这里，我们简要回顾了MAPT在散发性和家族性神经退行性疾病中的作用，然后讨论了最近的工作，第一次，提出了功能机制，MAPT单倍型与患者中看到的神经病理学。
The microtubule associated protein tau (MAPT) locus has long been associated with sporadic neurodegenerative disease, notably progressive supranuclear palsy and corticobasal degeneration, and more recently with Alzheimer’s disease and Parkinson’s disease. However, the functional biological mechanisms behind the genetic association have only now started to emerge. The genomic architecture in the region spanning MAPT is highly complex, and includes a ~1.8 Mb block of linkage disequilibrium (LD). The region is divided into two major haplotypes, H1 and H2, defined by numerous single nucleotide polymorphisms and a 900 kb inversion which suppresses recombination. Fine mapping of the MAPT region has identified sub-clades of the MAPT H1 haplotype which are specifically associated with neurodegenerative disease. Here we briefly review the role of MAPT in sporadic and familial neurodegenerative disease, and then discuss recent work which, for the first time, proposes functional mechanisms to link MAPT haplotypes with the neuropathology seen in patients.
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