本课题组在先前的研究中首次从世居藏族人群中筛选出 EGLN1、EPAS1、PTEN等10个与低氧适应相关的正选基因，后续的研究发现上述正选基因在高原蒙古族中同样具有多态性差异。最新的研究显示EGLN1等5个正选基因的单倍体分型差异与慢性高原具有很强的相关性，提示上述正选基因单倍体分型差异在低氧适应及CMS的发生发展过程中可能发挥一定的调控作用。为了进一步阐明上述基因单倍体分型差异的功能，本课题拟采用基因组捕获测序、转录组测序、转基因动物、荧光素酶报告法等分子生物学技术结合Hb、SaO2、肺动脉压等生理指标，在后基因组水平上研究正选基因转录激活区、编码区、转录后调控区单倍体分型差异的生物学功能，并建立以正选基因、miRNAs为作用基础的低氧ceRNAs调控网络，为低氧适应的基础研究及CMS发病机制提供新的理论依据，也为急慢性高原病的诊断、预防与治疗提供新的分子靶标。

Based on our previous genome-wide scans, we identified that positively selected haplotypes of EGLN1,EPAS1 and PPARA were significantly associated with high-altitude adaptation to this highland Tibetans. Recent results were shown that highland Mongolians shared hypoxia positively genes with Tibetan populations. Lasted results were shown that haplotype of EPAS1, EGLN1, EDNRA, CYP2E1 and PTEN were associated with chronic mountain sickness. It was indicating that positively selected genes may play an important role in CMS and hypoxia adaptation. To further identify the biological function of positively genes haplotypes and the mechanism of CMS,molecular biology assays(genetic seqencing,transcription seqencing,transgene animal,Lucimerse reporting assays, and so on) combined with physiological determination (HCT, Hb,SaO2,pulmonary arterial pressure and so on) were utilized to investigate the biological function of positively selected haplotypes in coding reign, transcriptional activation reign and post-transcriptional regulation reign at post-genome level, and establish a ceRNAs regulation signaling network based on positively gene and miRNAs. It will provide a new theoretical basis for hypoxia adaptation but also provide a new high altitude disease screening and diagnosis molecular target.