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.
Department of Gynecology and Obstetrics, The First Affiliated Hospital, Chongqiang Medical University, Chongqing, China.
Tian
T
Gao
Yanli
Y
Nie
Jianxin
J
Guo
D001324:Autoantigens / Q000235:genetics*; D016022:Case-Control Studies; D016000:Cluster Analysis; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006720:Homozygote; D006801:Humans; D025202:Molecular Diagnostic Techniques; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D011401:Promoter Regions, Genetic; D012261:Ribonucleoproteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017086:beta-Thalassemia / Q000175:diagnosis* / Q000235:genetics; D000097585:SS-B Antigen
D001324:Autoantigens; D005819:Genetic Markers; D012261:Ribonucleoproteins; D000097585:SS-B Antigen