应用全外显子组测序筛查一高原肺水肿家系易感基因

发布时间：2018-06-01 09:14

本文选题：高原肺水肿 + 家系　；参考：《遗传》2017年02期

【摘要】：高原肺水肿(high-altitude pulmonary edema,HAPE)是一种高原特发性疾病,其发病与遗传因素有一定关联。本研究对一个HAPE相关的家系展开遗传学调查,然后利用外显子组测序筛查了包括先证者在内的6名HAPE病史成员以及先证者的母亲共7个成员的遗传变异,结果发现18个HAPE相关的潜在遗传变异(9个SNVs和9个Indels)。利用SIFT,Poly Phen-2和PROVEAN等3种软件对这些遗传变异进行蛋白功能危害性分析,结果发现定位于CFHR4基因的SNV(p.L85F)以及定位于OXER1基因的SNV(p.R176C)具有高危害性,且OXER1的功能与HAPE低氧诱导通路存在高度关联,它们可作为该家系中HAPE相关的候选病理性变异。此外,还有部分SNVs(NMB p.S150P、APOB p.I4194T和EIF4ENIF1 p.Q763P)以及Indels(KCNJ12 p.EE333-334E、ANKRD31p.LMN251-253LN和OR2A14 p.HFFC175-178HFC),其遗传变异同样具有一定危害,可作为潜在的HAPE相关遗传变异。本研究首次通过外显子组测序直接筛选与一中国HAPE家系相关的遗传变异,为后续揭示HAPE发病机制提供了新线索。
[Abstract]:High altitude pulmonary (HAPE) is a high altitude idiopathic disease, which is associated with genetic factors. In this study, genetic investigation was carried out on a family associated with HAPE, and the genetic variation of 6 HAPE history members, including the proband, and 7 members of the mother of the proband were screened using exon group sequencing. The results showed that there were 18 potential genetic variations associated with HAPE (9 SNVs and 9 Indels). Using sift Phen-2 and PROVEAN to analyze the protein function hazard of these genetic variations, it was found that SNVP. L85F) and SNVp.R176C, which were located in CFHR4 gene and OXER1 gene, were highly harmful. The function of OXER1 is highly correlated with HAPE hypoxia induced pathway, and they can be used as candidate pathological variation of HAPE in this family. In addition, some SNVs(NMB p.S150PnAPOB p.I4194T and EIF4ENIF1 p.Q763P), Indels(KCNJ12 p.EE333-334EKRD31p. LMN251-253LN and OR2A14 p.HFFC175-178HFCN also have some harm, which can be used as potential HAPE related genetic variation. In this study, the genetic variation associated with a Chinese HAPE pedigree was screened directly by exon sequencing for the first time, which provided a new clue for further revealing the pathogenesis of HAPE.
【作者单位】：青海大学医学院高原医学研究中心;青海省高原医学应用基础重点实验室;青海-犹他高原医学联合重点实验室;青海省人民医院;青海大学医学院;
【基金】：国家自然科学基金项目(编号:31160232) 青海省科技厅应用基础基金项目(编号:2016-ZJ-706)资助~~
【分类号】：R594.3

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