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Reduced representation bisulfite sequencing (RRBS) involves restriction enzyme digestion and size selection of the digested DNA fragments to generate the representative samplings before bisulfite conversion and sequencing. RRBS improved the efficiency of the utilization of tissue samples and reduced the cost compared to deep depth of whole genome methylation study. As a high cost-effective tool of methylation study, it has extensive application prospects in the research with large scale clinical samples.