Mechanism of abnormalities in clinical laboratory data by analysis of epigenome, genome and miRome

即使是真正的Le阴性患者，他们基因上缺乏Le酶，理论上也不会产生CA19-9，偶尔也会出现血清CA19-9水平的轻微升高。我们分析了这一机制，发现这种现象发生在se阴性基因型纯合子的患者和CA19-9前体多糖过量产生的晚期癌症患者。人类基因组是由大量的区隔结构组成的，包括与染色体带相关的复制时序区和长链GC%镶嵌结构。我们发现，复制时间的早/晚开关区域通常与GC含量的转变相对应，与R/ g染色体带边界相关，而人类基因组中的这些特定区域对应于基因组中DNA损伤增加的“不稳定”区域。通过全基因组复制时间研究获得的信息将大大有助于我们理解疾病发病机制中的分子机制。

Even genuinely Le-negative patients, who genetically lack the Le enzyme and theoretically never produce CA19-9, occasionally show a slight increase in serum CA19-9 level. We analyzed this mechanism and found the phenomena are occurred when the patients are homozygous for Se-negative genotypes and suffer from advanced cancer with overproduction of glycans as precursors of CA19-9.The human genome is composed of large-scale compartmentalized structures, including replication-timing zones and long-range GC% mosaic structures, which are related to chromosome bands. We found that the early/late-switch regions of replication timing, which generally correspond with transitions in GC content, are correlated with R/G-chromosome band boundaries, and such specific regions in the human genome correspond to "unstable" regions of the genome in which increased DNA damage occurs. Information acquired through genome-wide studies of replication timing will contribute substantially to our understanding of the molecular mechanisms in the pathogenesis of diseases.