Integrated analysis of the critical region 5p15.3–p15.2 associated with cri-du-chat syndrome
Integrated analysis of the critical region 5p15.3–p15.2 associated with cri-du-chat syndrome
复制标题
DOI：
10.1590/1678-4685-gmb-2018-0173
复制
发表时间：
2019-01-01
影响因子：
2.1
通讯作者：
Riegel, Mariluce
中科院分区：
文献类型：
--
作者：
Corrêa, Thiago;Feltes, Bruno César;Riegel, Mariluce
Cri-du-chat 综合征 (CdCs) 是最常见的邻近基因综合征之一，其发病率为 1:15,000 至 1:50,000 活产。为了在分子水平上更好地了解 CdC 的病因学，我们利用系统生物学研究了与 CdC 相关的关键染色体区域 5p 15.3-p 15.2 内的蛋白质-蛋白质相互作用 (PPI) 网络。数据是从 CdC 患者的细胞基因组学结果中提取的。基于临床发现、染色体重排的分子特征和系统生物学数据，我们探索了涉及与 CdCs 候选基因相关的生物过程的可能的基因型-表型相关性。我们鉴定了涉及先前发现与 CdCs 相关的基因的生物过程，例如 TERT、SLC6A3 和 CTDNND2，以及对 CdCs 表型有潜在贡献的新型候选蛋白，包括 CCT5、TPPP、MED10、ADCY2、MTRR、CEP72、NDUFS6 和 MRPL36。尽管需要对这些蛋白质进行进一步的功能分析，但我们确定了用于开发新的多目标基因编辑工具来研究 CdC 的候选蛋白质。进一步的研究可能会证实那些直接参与 CdCs 表型发展的因素，并提高我们对 CdCs 相关分子机制的理解。
Cri-du-chat syndrome (CdCs) is one of the most common contiguous gene syndromes, with an incidence of 1:15,000 to 1:50,000 live births. To better understand the etiology of CdCs at the molecular level, we investigated theprotein-protein interaction (PPI) network within the critical chromosomal region 5p 15.3-p 15.2 associated with CdCs using systemsbiology. Data were extracted from cytogenomic findings from patients with CdCs. Based on clinical findings, molecular characterization of chromosomal rearrangements, and systems biology data, we explored possible genotype-phenotype correlations involving biological processes connected with CdCs candidate genes. We identified biological processes involving genes previously found to be associated with CdCs, such as TERT, SLC6A3, and CTDNND2, as well as novel candidate proteins with potential contributions to CdCs phenotypes, including CCT5, TPPP, MED10, ADCY2, MTRR, CEP72, NDUFS6, and MRPL36. Although further functional analyses of these proteins are required, we identified candidate proteins for the development of new multi-target genetic editing tools to study CdCs. Further research may confirm those that are directly involved in the development of CdCs phenotypes and improve our understanding of CdCs-associated molecular mechanisms.