SIT Consulting-Science, Innovation & Technology, Cali 76001, Colombia.
Laboratory of Molecular Biology and Pathogenesis, Department of Physiological Sciences, School of Basic Sciences, Faculty of Health, Universidad del Valle, Cali 76001, Colombia.
Genes (Basel). 2022 Apr 1;13(4):628. doi: 10.3390/genes13040628.
Although Down syndrome (DS) is the most frequent human chromosomal disorder and it causes mainly intellectual disability, its clinical presentation is complex and variable.
We aimed to analyze and compare the transcriptome disruption in several brain areas from individuals with DS and euploid controls as a new approach to consider a global systemic differential disruption of gene expression beyond chromosome 21.
We used data from a DNA microarray experiment with ID GSE59630 previously deposited in the GEO DataSet of NCBI database. The array contained log2 values of 17,537 human genes expressed in several aeras of the human brain. We calculated the differential gene expression (Z-ratio) of all genes.
We found several differences in gene expression along the DS brain transcriptome, not only in the genes located at chromosome 21 but in other chromosomes. Moreover, we registered the lowest Z-ratio correlation between the age ranks of 16-22 weeks of gestation and 39-42 years (R = 0.06) and the highest Z-ratio correlation between the age ranks of 30-39 years and 40-42 years (R = 0.89). The analysis per brain areas showed that the hippocampus and the cerebellar cortex had the most different gene expression pattern when compared to the brain as a whole.
Our results support the hypothesis of a systemic imbalance of brain protein homeostasis, or proteostasis network of cognitive and neuroplasticity process, as new model to explain the important effect on the neurophenotype of trisomy that occur not only in the loci of chromosome 21 but also in genes located in other chromosomes.
唐氏综合征（DS）是最常见的人类染色体疾病，主要导致智力障碍，但临床表现复杂且多变。
我们旨在分析和比较 DS 个体与正常二倍体对照者几个脑区的转录组紊乱，作为一种新方法，考虑 21 号染色体以外的基因表达的全身性系统差异失调。
我们使用先前在 NCBI 的 GEO 数据集数据库中存储的 ID GSE59630 的 DNA 微阵列实验数据。该阵列包含了在人类大脑的多个区域表达的 17537 个人类基因的 log2 值。我们计算了所有基因的差异基因表达（Z 比）。
我们发现 DS 大脑转录组中存在多种基因表达差异，不仅在 21 号染色体上的基因，而且在其他染色体上的基因。此外，我们记录了妊娠 16-22 周和 39-42 岁年龄等级之间的 Z 比相关性最低（R=0.06），而 30-39 岁和 40-42 岁年龄等级之间的 Z 比相关性最高（R=0.89）。按脑区进行的分析表明，与整个大脑相比，海马体和小脑皮质的基因表达模式差异最大。
我们的结果支持了大脑蛋白质平衡或认知和神经可塑性过程的蛋白质组网络的系统失衡的假说，作为解释 21 号染色体以外的基因以及其他染色体上的基因对三体神经表型的重要影响的新模型。
