Genetic variants at the EGLN1 locus associated with high-altitude adaptation in Tibetans are absent or found at low frequency in highland Andeans.
Genetic variants at the EGLN1 locus associated with high-altitude adaptation in Tibetans are absent or found at low frequency in highland Andeans.
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DOI：
10.1111/ahg.12299
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发表时间：
2019-05
影响因子：
1.9
通讯作者：
Simonson TS
中科院分区：
文献类型：
--
作者：
Heinrich EC;Wu L;Lawrence ES;Cole AM;Anza-Ramirez C;Villafuerte FC;Simonson TS
EGLN 1编码低氧诱导因子（HIF）途径脯氨酰羟化酶2（PHD 2），其作为HIF活性的氧敏感性调节剂。EGLN 1基因座在西藏和安第斯人群中表现出正选择的特征，并与西藏人的血红蛋白浓度相关。最近的报告提供了证据，表明EGLN 1第一外显子（rs 186996510，rs 12097901）内的蛋白质编码变体与西藏人的适应信号有关，但这些相同的变体是否存在并有助于安第斯高地人的适应尚不清楚。我们确定了这些适应性西藏等位基因的频率在克丘亚安第斯居民在高海拔（4,350米），除了个人的尼泊尔祖先居住在海平面。以前在藏族中发现的高频率rs 186996510 C（次要）等位基因在安第斯山脉中不存在（G：100%），在尼泊尔人中也很少见（C：11.8%，G：88.2%）。与藏人相比，在安第斯人（G：12.7%，C：87.3%）和尼泊尔人（G：23.5%，C：76.5%）中发现次要G等位基因rs 12097901的频率同样低。这些结果表明，在安第斯山脉涉及EGLN 1的适应涉及不同的机制比那些在西藏人描述。精确的安第斯适应变量仍有待确定。
EGLN1 encodes the hypoxia-inducible factor (HIF) pathway prolyl hydroxylase 2 (PHD2) that serves as an oxygen-sensitive regulator of HIF activity. The EGLN1 locus exhibits a signature of positive selection in Tibetan and Andean populations and is associated with hemoglobin concentration in Tibetans. Recent reports provide evidence for functional roles of protein-coding variants within the first exon of EGLN1 (rs186996510, rs12097901) that are linked to an adaptive signal in Tibetans, yet whether these same variants are present and contribute to adaptation in Andean highlanders is unknown. We determined the frequencies of these adaptive Tibetan alleles in Quechua Andeans resident at high altitude (4,350 m) in addition to individuals of Nepali ancestry resident at sea level. The rs186996510 C (minor) allele previously found at high frequency in Tibetans is absent in Andean (G: 100%) and rare among Nepali (C: 11.8%, G: 88.2%) cohorts. The minor G allele of rs12097901 is found at similarly low frequencies in Andeans (G: 12.7%, C: 87.3%) and Nepalis (G: 23.5%, C: 76.5%) compared to Tibetans. These results suggest that adaptation involving EGLN1 in Andeans involves different mechanisms than those described in Tibetans. The precise Andean adaptive variants remain to be determined.
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DOI：
10.1042/bj20140754
发表时间：
2014-09-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Shmakova A;Batie M;Druker J;Rocha S
通讯作者：
Rocha S
影响因子：
56.9
作者：
Jaakkola, P;Mole, DR;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
影响因子：
2.9
作者：
Bigham, Abigail W.;Wilson, Megan J.;Shriver, Mark D.
通讯作者：
Shriver, Mark D.
影响因子：
4.8
作者：
Song, Daisheng;Li, Lin-Sheng;Lee, Frank S.
通讯作者：
Lee, Frank S.
影响因子：
10.7
作者：
Peng, Yi;Yang, Zhaohui;Su, Bing
通讯作者：
Su, Bing