中文摘要
众多研究表明遗传变异是非自杀性自伤行为(NSSI)的重要影响因素,而内含子遗传变异与NSSI的关联及作用机制未见报道。近年,由内含子转录的非编码RNA,特别是长链非编码(lnc)RNA调控基因表达而影响疾病发生及预后受到重点关注。我们最近通过全基因组芯片和生物信息学分析,推测脑源性神经营养因子(BDNF)基因内含子rs11822590和rs11825029可能通过影响lncRNA BDNF-AS和LINC00678的功能影响NSSI的易感性。本课题拟通过大样本人群在验证rs11822590和rs11825029与NSSI关联的基础上,运用RT-PCR、RNA Pull-down、Western Blot等分子生物学技术探索其影响BDNF-AS和LINC00678从转录后水平调控BDNF表达的分子机制,这一研究可能会在揭示NSSI的遗传病因机制上有所突破,并为NSSI预防和诊断提供新靶点。
英文摘要
It is reported that genetic variation is an important risk factor for non-suicidal self-injury (NSSI) among adolescents, however, there is no study have been explored the association between intron genetic variation and NSSI, neither their action mechanism. Most recently, it has been shown that non-coding RNA (ncRNA), especially long non-coding (lnc) RNA, which is transcribed by introns, play an important role in development and prognosis of disease through regulating gene expression. Results from the whole genome microarray and bioinformatics analysis have shown that two introns, rs11822590 and rs11825029, in brain-derived neurotrophic factor (BDNF) gene, may effect NSSI susceptibility through influencing the functions of lncRNA BDNF-AS and LINC00678, which encoded by the introns in BDNF. Therefore, the current study aims to estimate the association between rs11822590 and rs11825029 and NSSI with a large sample of population, and to explore the molecular mechanism of intron genetic variation affect BDNF-AS and LINC00678 regulate BDNF expression in post transcriptional level, RT-PCR, RNA Pull-down, western-blot and other molecular biological techniques will be used in the process of data collection. The current study may shed light on the genetic mechanism of NSSI and provide new targets for the prevention and diagnosis of NSSI.
