Genome-wide methylation and gene-expression analyses in thalassemia

作者：Wei Zhang, Xiaokang Li, Uet Yu, Xin Huang, Hongmei Wang, Yi Lu, Sixi Liu, Jian Zhang · 发表于：Aging · 年份：2024 · DOI：10.18632/aging.206037 · 被引用次数：3 · 研究领域：Hemoglobinopathies and Related Disorders、Epigenetics and DNA Methylation、Iron Metabolism and Disorders

Thalassemia is the most common autosomal genetic disorder in humans. The pathogenesis of thalassemia is principally due to the deletion or mutation of globin genes that then leads to disorders in globin-chain synthesis, and its predominant clinical manifestations include chronic forms of hemolytic anemia. However, research on the epigenetics and underlying pathogenesis of thalassemia is in its nascency and not yet been systematically realized. In this study, we compared the results of RNA-seq and the whole-genome bisulfite sequencing (WGBS) on 22 peripheral blood samples from 14 thalassemic patients and eight healthy individuals revealed a genome-wide methylation landscape of differentially methylated regions (DMRs). And functional-enrichment analysis revealed the enriched biological pathways with respect to the differentially expressed genes (DEGs) and differentially methylated genes (DMGs) to include hematopoietic lineage, glucose metabolism, and ribosome. To further analyze the interaction between the transcriptome and methylome, we implemented a comprehensive analysis of overlaps between DEGs and DMGs, and observed that biological processes significantly enriched the immune-related genes (i.e., our hypermethylated and down-regulated gene group). Hypermethylated and hypomethylated regions of thalassemia-related genes exhibited different distribution patterns. We thus, further identified and validated thalassemia-associated DMGs and DEGs by multi-omics integrative analyses ...