Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
Sci Rep. 2018 Jul 4;8(1):10091. doi: 10.1038/s41598-018-28375-0.
Turner Syndrome (TS) is a condition where several genes are affected but the molecular mechanism remains unknown. Identifying the genes that regulate the TS network is one of the main challenges in understanding its aetiology. Here, we studied the regulatory network from manually curated genes reported in the literature and identified essential proteins involved in TS. The power-law distribution analysis showed that TS network carries scale-free hierarchical fractal attributes. This organization of the network maintained the self-ruled constitution of nodes at various levels without having centrality-lethality control systems. Out of twenty-seven genes culminating into leading hubs in the network, we identified two key regulators (KRs) i.e. KDM6A and BDNF. These KRs serve as the backbone for all the network activities. Removal of KRs does not cause its breakdown, rather a change in the topological properties was observed. Since essential proteins are evolutionarily conserved, the orthologs of selected interacting proteins in C. elegans, cat and macaque monkey (lower to higher level organisms) were identified. We deciphered three important interologs i.e. KDM6A-WDR5, KDM6A-ASH2L and WDR5-ASH2L that form a triangular motif. In conclusion, these KRs and identified interologs are expected to regulate the TS network signifying their biological importance.
特纳综合征（TS）是一种受多个基因影响但分子机制尚不清楚的疾病。鉴定调节 TS 网络的基因是理解其发病机制的主要挑战之一。在这里，我们研究了文献中报道的人工策展基因的调控网络，并鉴定了与 TS 相关的必需蛋白。幂律分布分析表明，TS 网络具有无标度层次分形属性。这种网络组织在没有中心致命控制系统的情况下，保持了各级节点的自治结构。在网络中形成主导枢纽的二十七个基因中，我们鉴定出两个关键调节剂（KRs），即 KDM6A 和 BDNF。这些 KRs 是所有网络活动的基础。去除 KRs 不会导致其崩溃，而是观察到拓扑性质的变化。由于必需蛋白在进化上是保守的，因此鉴定了秀丽隐杆线虫、猫和猕猴（从低等到高等生物）中所选相互作用蛋白的同源物。我们揭示了三个重要的相互作用蛋白，即 KDM6A-WDR5、KDM6A-ASH2L 和 WDR5-ASH2L，它们形成了一个三角形基序。总之，这些 KR 和鉴定的相互作用蛋白有望调节 TS 网络，表明它们具有重要的生物学意义。
