应用全外显子组测序筛查一高原肺水肿家系易感基因

doi:10.16288/j.yczz.16-288

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Hereditas(Beijing) ›› 2017, Vol. 39 ›› Issue (2): 135-142.doi: 10.16288/j.yczz.16-288

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The susceptibility gene screening in a Chinese high-altitude pulmonary edema family by whole-exome sequencing

Yingzhong Yang^1,^4,⁵(),Yaping Wang²,Jin Xu³,Rili Ge^1,^4,⁵(),

1. Research Center for High Altitude Medical Science, Qinghai University School of Medicine, Xining 810001, China
2. Department of Internal Medicine, Qinghai Provincial People's Hospital, Xining 810007, China
3. Qinghai University School of Medicine, Xining 810001, China
4. Basic and Applied Key Laboratory for High Altitude Medical Science and Technology of Qinghai, Xining 810001, China
5. Qinghai-Utah United Key Laboratory for High Altitude Medical Science, Xining 810001, China

Received:2016-11-04 Revised:2017-01-04 Online:2017-01-12 Published:2017-01-12
Supported by:
the National Natural Science Foundation of China(31160232);Basic Applied Study Foundation of Qinghai(2016-ZJ-706)

Abstract

Abstract:

High-altitude pulmonary edema (HAPE) is one of idiopathic mountain sicknesses that occur in healthy lowlanders when they quickly ascend to altitudes exceeding 2500 m above sea levels within 1-7 days. Growing evidence suggests that genetics plays an important role in the risk of HAPE. In this study, we recruited a Chinese HAPE family and screened genetic variations in the 7 family members (including 6 family members with a medical history of HAPE and the propositus's mother) by whole-exome sequencing. The results showed 18 genetic variations (9 SNVs and 9 Indels) were related to HAPE. Two SNV sites (CFHR4 (p.L85F) and OXER1 (p.R176C)) were predicted to be damaging and alter protein functions by SIFT, PolyPhen-2 and PROVEAN software. The biological function of OXER1 was highly related to the hypoxia-inducible factor pathway. Therefore, those two sites were identified as candidate pathological variations. Moreover, other SNVs (NMB p.S150P, APOB p.I4194T, EIF4ENIF1 p.Q763P) and Indels (KCNJ12 p.EE333-334E, ANKRD31 p.LMN251-253LN, OR2A14 p.HFFC175-178HFC) were also predicted to be damaging as well, which also might be considered as potential candidate pathological variations related to HAPE. Collectively we firstly screened the susceptibility genes in a Chinese HAPE family by whole-exome sequencing, which will provide new clues for further mechanistic studies of HAPE.

Key words: HAPE, family, whole-exome sequencing, CFHR4, OXER1

Yingzhong Yang, Yaping Wang, Jin Xu, Rili Ge, . The susceptibility gene screening in a Chinese high-altitude pulmonary edema family by whole-exome sequencing[J]. Hereditas(Beijing), 2017, 39(2): 135-142.

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