印记基因的产生、调控机制及相关疾病的研究进展

Research Progress in Generation,Regulatory Mechanisms of Imprinted Genes and Related Diseases

印记基因广泛存在于哺乳动物中,其有序调节并表达对正常胚胎及出生后个体的生长发育至关重要。印记基因的维持、擦除和重建主要通过以DNA甲基化为主的表观遗传修饰实现。印记基因簇的常见调控模型为绝缘子模型和长链非编码RNA模型。印记基因的表达紊乱与人类多种疾病密切相关,Igf2/H19紊乱会导致Beckwith-Wiedemann综合征或Silver-Russell综合征;Snurf-Snrpn紊乱会导致Angelman综合征或Prader-Willi综合征;Igf2r/Airn、Kcnq1/Kcnqlot1和Dlk1-Dio3的紊乱与肿瘤、中枢神经系统退行性疾病等相关。研究印记基因对于阐明相关疾病发病机制和发现治疗靶点具有重要意义。

Imprinted genes are present widely in mammals.Orderly regulation and expression of imprinted genes are essential for normal embryonic and postnatal individual growth and development.Maintenance,erasure and reconstruction of imprinted genes are mainly achieved through epigenetic modifications dominated by methylation of DNA.The common regulation models of imprinted gene clusters are insulator models and long non-coding RNA models.Disorders in the expression of imprinted genes are closely associated with a variety of human diseases,Igf2/H19 disorders can lead to Beckwith-Wiedemann syndrome or Silver-Russell syndrome;Snurf-Snrpn disorders can lead to Angelman syndrome or Prader-Willi syndrome;Igf2r/Airn,Kcnq1/Kcnqlot1 and Dlk1-Dio3 disorders are associated with tumors and degeneration of the central nervous system,etc.The study of imprinted genes is important for both elucidating the pathogenesis and discovering therapeutic targets of related diseases.