Blood: Enhanced subgene recombination mediates the occurrence of platelet disease in Quebec.

!----: In QPD, PLAU repetition disrupts genomic structure, alters the interaction of the enhanced subgene and gene, and leads to overexpression of cell type specificity.Abstract: Quebec platelet disorder (QPD) is an autosomal dominant hemorrhagic disease in which a unique, platelet-dependent function is defective in fibrin dissolution, but not accompanied by systemic fibrin dissolution.the hallmark of QPD is that PLAU-specific overexpression is more than 100 times in macronuclear cells.this overexpression resulted in an increase of more than 100 times the platelet storage of the urinary kinase lysozysolysolysolysolysoactive (PLAU/uPA), followed by the degradation of various a-particle proteins mediated by the lysozyzyme, and the accelerated fibrosis of platelet-dependent.the mutation that caused the above is a 78kb series of repeat sequences of PLAU.the mechanism by which this repetition leads to macrophage-specific PLAU overexpression is unclear.to study the mechanism of triggering QPD, Liang and others used epigenetic analysis, comparative genomics, and chromatin conformation altruism capture methods to study PLAU regulation in cultured macronuclear cells from controlled sources in Patients with QPD and Non-QPD.results show that QPD repetition causes an ectopic interaction between PLAU and a conservative macronuclear cell enhancers found in the same topological association domain (TAD).the results of this study support a unique disease mechanism, the recombination of the sub-TAD genome structure, leading to a dramatic, cell-specific phenotype of blood disease..