Integrated Quantitative Neuro-transcriptome Analysis of Several Brain Areas in Human Trisomy 21
Abstract Background Although Down syndrome (DS) is a trisomy of chromosome 21 being the most frequent human chromosomal disorder mainly associated with variables dysfunctions. Objective In this context, we aimed to analyze and compare the disruption of transcriptome of 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 of chromosome 21. Methods 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 human brain. We calculated the differential gene expression (Z-ratio) of all genes. Results 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 2 = 0.06) and the highest Z-ratio correlation between the age ranks of 30–39 years and 40–42 years (R 2 = 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. Conclusions 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 loci of chromosome 21 but also in genes located in other chromosomes.