Abstract:
Down’s syndrome is the most common genetic aberration with the frequency
of one in 700 live births worldwide. The most alarming situation for the patients
with Down’s syndrome is the presence of accompanying neurological, congenital
heart, intestinal, neuromuscular and immune system disorders. Supernumerary of
chromosome 21(HSA21) is due to the different mechanisms such as chromosome
non-disjunction during meiosis II, translocation of chromosome and mosaicism. Age,
lifestyle and diet of the mother are the main risk factors which elevate the occurrence
of DS in newborn. Since HSA21 sequenced in 2000, scientists explored the relation
of other disorders with DS. Although, many disorders caused by trisomy but the exact
pathways that lead to these disorders are still unclear. Previously, differentially
expressed genes and pathways related to the DS found either by microarray or RNAsequencing
data separately or by using just one type of tissue samples. In this research,
we looked into the holistic picture of DS by comparative analysis of microarray and
RNA-sequencing data of different tissue samples as well as by investigating weighted
co-expressed gene modules. For this analysis, 4 microarray datasets and 3 RNAsequencing
datasets obtained from publicly available databases. We found CFAP298
(Cilia And Flagella Associated Protein 298) common gene in all datasets. There
were 3 common genes in microarray datasets and 37 common genes in RNA-seq
datasets found out. There was no common enriched pathway obtained in comparative
analysis of individual gene set enrichment analysis of all datasets. Weighted gene
co-expression analysis obtained modules of co expressed hub genes in DS. GSEA
of selected hub genes resulted into the 25 significant enriched pathways. The most
enriched and significant up-regulated pathways contain pathways of staphylococcus
aureus infection, DNA replication, cell adhesion molecules, phagosome, cell cycle,
oocyte meiosis, progesterone-mediated oocyte maturation, fanconi anemia pathway,
bile secretion and cholesterol metabolism. On the other hand herpes simplex virus 1
1
Abstract
infection, tight junction, cytokine-cytokine receptor interaction, thyroid cancer pathways
and legionellosis are down-regulated pathways.
