Hypermethylation of the gene LARP2 for noninvasive prenatal diagnosis of β-thalassemia based on DNA methylation profile
In order to identify epigenetic markers of β-thalassemia, a genome-wide profiling method named differential methylation hybridization was used to search these differentially methylated genes. Unsupervised hierarchical clustering and molecular annotation system were used to analyze the data, and methylation-specific PCR and real-time PCR were used to confirm the differentially methylated genes. This system was validated by detecting 13 cases, 10 of which were homo-zygous β-thalassaemia. Totally 113 genes were identified as methlyation-enriched genes (ratio ≥ 2.0, P < 0.05) and 96 genes were identified as hypomethylated genes in both groups (ratio ≤ 0.5, P < 0.05). The promoter of the gene of La ribonucleoprotein domain family (LARP2) was significantly hypermethylated in β-thalassemia, and the expression of LARP2 was significantly lower in β-thalassemia. Hypermethylation of the LARP2 promoter was correlated with its lower expression in β-thalassemia and our chip-based DNA methylation detection system can provide earlier diagnosis of β-thalassemia using this epigenetic marker.
Keywordsβ-Thalassemia LARP2 DNA methylation profile Bioinformatics DMH MAS
This work is supported by National Nature Science Foundation (31001010) and Natural Science Foundation Project of CQ CSTC (cstcjjA10092).
Conflict of interest
These authors fully declare any financial or other potential conflict of interest.
- 1.Ashraf EKI, Natalie PT (2006) MMASS: an optimized array-based method for assessing CpG island methylation. Nucleic Acids Res 20(34):e136–e148Google Scholar
- 7.Bottardi S, Aumont A, Grosveld F (2003) Developmental stage-specific epigenetic control of human-globin gene expression is potentiated in hematopoietic progenitor cells prior to their transcriptional activation. Blood 5:1540–1569Google Scholar
- 17.Gurvich N, Berman MG, Wittner BS et al (2004) Association of valproate-induced teratogenesis with histone deacetylase inhibition in vivo. FASEB J 9:1166–1168Google Scholar
- 26.Parrella P, Torre A, Copetti M (2009) High specificity of quantitative methylation-specific PCR analysis for MGMT promoter hypermethylation detection in gliomas. J Biomed Biotechnol 10:1155–1163Google Scholar
- 28.Ross J, Bottardi S, Bourgoin V (2009) Differential requirement of a distal regulatory region for pre-initiation complex formation at globin gene promoters. Nucleic Acids Res. doi: 10.1093/nar/gkp545
- 32.Steven AB (2004) Gene-promoter hypermethylation as a biomarker in lung cancer. Nat Rev 4:1038–1049Google Scholar
- 33.Sun H, Palaniswamy SK, Pohar TT (2006) MPromDb: an integrated resource for annotation and visualization of mammalian gene promoters and ChIP-chip experimental data. Nucleic Acids Res 34:99–103Google Scholar
- 39.Yan PS, Chen CM, Shi H (2002) Applications of CpG island microarrays for high-throughput analysis of DNA methylation. J Nutr 132:S2430–S2434Google Scholar
- 41.Zare M, Jazii FR, Alivand MR (2009) Qualitative analysis of adenomatous polyposis coli promoter: hypermethylation, engagement and effects on survival of patients with esophageal cancer in a high risk region of the world, a potential molecular marker. BMC Cancer 10:1186–1198Google Scholar