Abstract
Down syndrome (DS) is caused by triplication of Human chromosome 21 (Hsa21) and associated with an array of deleterious phenotypes, including mental retardation, heart defects and immunodeficiency. Genome-wide expression patterns of uncultured peripheral blood cells are useful to understanding of DS-associated immune dysfunction. We used a Human Exon microarray to characterize gene expression in uncultured peripheral blood cells derived from DS individuals and age-matched controls from two age groups: neonate (N) and child (C). A total of 174 transcript clusters (gene-level) with eight located on Hsa21 in N group and 383 transcript clusters including 56 on Hsa21 in C group were significantly dysregulated in DS individuals. Microarray data were validated by quantitative polymerase chain reaction. Functional analysis revealed that the dysregulated genes in DS were significantly enriched in two and six KEGG pathways in N and C group, respectively. These pathways included leukocyte trans-endothelial migration, B cell receptor signaling pathway and primary immunodeficiency, etc., which causally implicated dysfunctional immunity in DS. Our results provided a comprehensive picture of gene expression patterns in DS at the two developmental stages and pointed towards candidate genes and molecular pathways potentially associated with the immune dysfunction in DS.
Highlights
Down syndrome (DS; trisomy 21) is characterized by a complete, or occasionally partial, triplication of Hsa21
This suggests that the number of the expressed genes in DS and control cells was comparable in the two studies
Consistent with the observations of Prandini et al [12], gender and DS6gender effects were not significant for expressed Hsa21 genes in DS individuals; expression of some non-Hsa21 genes were significantly affected by the two effects in each group
Summary
Down syndrome (DS; trisomy 21) is characterized by a complete, or occasionally partial, triplication of Hsa. With an incidence of about one in 750 births [1], DS is the most common autosomal abnormality affecting live-born infants. DS patients are clinically associated with multiple blood cellrelated phenotypes, including increased risk to develop leukemia, decreased lymphocyte counts, markedly enhanced incidence of autoimmune disorders as well as vulnerability to recurrent bacterial and viral infections [3,4,5,6]. The molecular mechanisms by which trisomy 21 leads to the immune system disorders in DS remain poorly investigated. Several gene-expression studies in T lymphocytes [9] and blood cells [10] from DS patients reported dysregulated expression of some immune-associated genes, yet very small sample size or ageunmatched controls restricted statistical analysis
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