Department of Genetics, Institute of Biosciences, Federal University of Rio Grande do Sul UFRGS, Porto Alegre 91501-970, Brazil.
Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro 20511-010, Brazil.
Genes (Basel). 2021 Apr 23;12(5):632. doi: 10.3390/genes12050632.
Chromosomal duplications are associated with a large group of human diseases that arise mainly from dosage imbalance of genes within the rearrangements. Phenotypes range widely but are often associated with global development delay, intellectual disability, autism spectrum disorders, and multiple congenital abnormalities. How different contiguous genes from a duplicated genomic region interact and dynamically affect the expression of each other remains unclear in most cases. Here, we report a genomic comparative delineation of genes located in duplicated chromosomal regions 8q24.13q24.3, 18p11.32p11.21, and Xq22.3q27.2 in three patients followed up at our genetics service who has the intellectual disability (ID) as a common phenotype. We integrated several genomic data levels by identification of gene content within the duplications, protein-protein interactions, and functional analysis on specific tissues. We found functional relationships among genes from three different duplicated chromosomal regions, reflecting interactions of protein-coding genes and their involvement in common cellular subnetworks. Furthermore, the sharing of common significant biological processes associated with ID has been demonstrated between proteins from the different chromosomal regions. Finally, we elaborated a shared model of pathways directly or indirectly related to the central nervous system (CNS), which could perturb cognitive function and lead to ID in the three duplication conditions.
染色体重复与一大类人类疾病有关，这些疾病主要源于重排中基因的剂量失衡。表型范围广泛，但通常与整体发育迟缓、智力障碍、自闭症谱系障碍和多种先天性异常有关。在大多数情况下，不同的连续基因如何从重复的基因组区域相互作用并动态影响彼此的表达仍不清楚。在这里，我们报告了在我们的遗传服务中跟踪的三个具有智力障碍（ID）这一常见表型的患者中，位于染色体重复区域 8q24.13q24.3、18p11.32p11.21 和 Xq22.3q27.2 中的基因的基因组比较描绘。我们通过鉴定重复区域内的基因内容、蛋白质-蛋白质相互作用和特定组织的功能分析，整合了几个基因组数据水平。我们发现了来自三个不同染色体重复区域的基因之间的功能关系，反映了蛋白质编码基因的相互作用及其在常见细胞子网络中的参与。此外，还证明了来自不同染色体区域的蛋白质之间存在与 ID 相关的共同显著生物学过程的共享。最后，我们详细阐述了与中枢神经系统（CNS）直接或间接相关的途径的共享模型，这可能会扰乱认知功能并导致这三种重复条件下的 ID。
