Figure 2.
Hierarchical cluster analysis of 112 significantly differentially expressed genes successfully segregates sickle cell disease from control patients. These genes were derived using 2-way ANOVA, false discovery rate multiple comparisons correction of less than or equal to 5%, more than or equal to 20% fold-change cut-off, and a mean average difference more than 20 filter in either the sickle cell disease or control group. These 112 genes were obtained comparing mean gene expression levels in 14 sickle cell disease patients of HbSS phenotype (not on hydroxyurea therapy) to 13 African-American control subjects. Hierarchical clustering was performed across a larger set of all sickle cell disease patients (HbSS phenotype only) in the study, including patients on hydroxyurea treatment, using these 112 genes. The dendrogram at the top of the figure represents the relatedness of samples based on gene expression patterns. The white line separates the 2 main branches of the dendrogram. With the exception of one sickle cell patient on hydroxyurea, these 112 genes successfully segregate control (AA) from sickle cell disease (SS or SS*) patients. Sickle cell disease patients on hydroxyurea (SS*) therapy do not cluster separately from patients not on therapy. The single sickle cell patient on hydroxyurea who clustered with the control group may represent a misclassification or hydroxyurea altered the gene expression toward a normalized pattern. Gene names appear to the right of the figure and those of particular interest to our group are underlined and highlighted in yellow.