Research Paper Volume 16, Issue 15 pp 11591—11605
Genome-wide methylation and gene-expression analyses in thalassemia
- 1 School of Medicine, Southern University of Science and Technology, Shenzhen 518055, Guangdong, China
- 2 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
- 3 Center for Reproductive Medicine, University of Hongkong-Shenzhen Hospital, Shenzhen 518053, Guangdong, China
- 4 Department of Hematology and Oncology, Shenzhen Children’s Hospital, Shenzhen 518038, Guangdong, China
- 5 Department of Infectious Diseases, Shenzhen Children’s Hospital, Shenzhen 518038, Guangdong, China
Received: December 5, 2023 Accepted: July 11, 2024 Published: August 9, 2024
https://doi.org/10.18632/aging.206037How to Cite
Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.