HSA21 gene expression between Down Syndrome and control cell lines

Background: Down syndrome is the most common genetic cause of mental retardation in humans, occurring in ~1 in 800 newborns. It is caused by chromosome 21 trisomy. Disruption of the phenotype is thought to be the result of gene dosage imbalance. The aim of the study was to classify chromosome 21 genes according to their level of expression in Down syndrome. Results: Variations in chromosome 21 gene expression were analyzed in lymphoblastoid cell lines derived from 10 Down syndrome patients and 11 control individuals. Of the 359 genes and predictions displayed on a specifically designed high content chromosome 21 oligoarray, 132 genes were expressed in lymphoblastoid cell lines. By using a powerful statistical analysis, 58 genes were found overexpressed and 42 unchanged in cell lines from Down syndrome patients. Microarray data were validated by quantitative PCR on 10 genes. Conclusions: The 132 chromosome 21 genes expressed by derived lymphoblastoid cell lines were classified into four categories: Class I: 24 genes controlled by the gene dosage effect with an increase in expression in Down syndrome between 1.4 and 1.6; Class II: 14 amplified genes with expression ratio above 1.6; Class III: 32 compensated genes with expression ratio between 0.82 to 1.4 and Class IV: 30 genes with high variability between individuals. Class I and II genes are likely to be involved in the Down syndrome phenotype, in contrast to the compensated Class III genes; Class IV genes could account for the variable phenotypes observed in patients. Keywords: HSA21 gene expression in Down syndrome We chose a design involving 40 arrays. Samples from a same patient are marked the same number of times with each fluorescent dye (Cy3 or Cy5). On each array a DS lymphoblastoid cell line and a control lymphoblastoid cell line were compared to increase the precision of the disease effect. Ten arrays compared either i) a male with DS versus a male without DS; ii) a female with DS versus a female without DS; iii) a male with DS versus a female without DS, and finally iv) a female with DS versus a male without DS.