Gene expression in blood from an individual with β-thalassemia: An RNA sequence analysis

Abstract

Background: Transcriptome profiling in individuals affected with β-thalassemia, especially in individuals who carry novel mutations in the HBB, may improve our understanding of the heterogeneity and molecular mechanisms of the disease. Methods: Members of a family with a daughter affected with thalassemia intermedia, although her mother was not clinically affected, were examined. We also characterized genome-wide gene expression in the family using real-time quantitative polymerase chain reaction and high-throughput RNA-sequencing mRNA expression profiling of blood. Results: We described the downregulation of the β-globin gene in β-thalassemia by RNA-sequencing analysis using a sample from an affected individual and her mother, who have a novel mutation in the HBB that creates a cryptic donor splice site. The daughter has a typical β-thalassemia allele as well, and an unexpectedly severe phenotype. The differentially expressed genes are enriched in pathways that are directly or indirectly related to β-thalassemia such as hemopoiesis, heme biosynthesis, response to oxidative stress, inflammatory responses, immune responses, control of circadian rhythm, apoptosis, and other cellular activities. Conclusion: We compare our findings with published results of RNA-sequencing analysis of sickle cell disease and erythroblasts from a KLF1-null neonate with hydrops fetalis, and recognize similarities and differences in their transcriptional expression patterns.