School of Medicine, Southern University of Science and Technology, Shenzhen 518055, Guangdong, China.
Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen 518055, Guangdong, China.
Aging (Albany NY). 2024 Aug 9;16(15):11591-11605. doi: 10.18632/aging.206037.
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 of DNA methylation and transcriptomics data, and provided a comprehensive genomic map of thalassemia that will facilitate the exploration of the epigenetics mechanisms and pathogenesis underlying thalassemia.
地中海贫血是人类最常见的常染色体遗传病。地中海贫血的发病机制主要是由于珠蛋白基因的缺失或突变，导致珠蛋白链合成紊乱，其主要临床表现为慢性溶血性贫血。然而，地中海贫血的表观遗传学和发病机制的研究还处于起步阶段，尚未得到系统的认识。在这项研究中，我们比较了来自 14 名地中海贫血患者和 8 名健康个体的 22 个外周血样本的 RNA-seq 和全基因组亚硫酸氢盐测序（WGBS）结果，揭示了一个全基因组甲基化差异区域（DMR）图谱。功能富集分析显示，差异表达基因（DEGs）和差异甲基化基因（DMGs）所富集的生物学途径包括造血谱系、葡萄糖代谢和核糖体。为了进一步分析转录组和甲基组之间的相互作用，我们对 DEGs 和 DMGs 之间的重叠进行了全面分析，观察到生物过程显著富集了与免疫相关的基因（即我们的高甲基化和下调基因组）。地中海贫血相关基因的高甲基化和低甲基化区域表现出不同的分布模式。因此，我们通过对 DNA 甲基化和转录组学数据的多组学综合分析，进一步鉴定和验证了与地中海贫血相关的 DMGs 和 DEGs，并提供了一个全面的地中海贫血基因组图谱，这将有助于探索地中海贫血的表观遗传学机制和发病机制。
