The genetic architecture of adaptations to high altitude in Ethiopia.
The genetic architecture of adaptations to high altitude in Ethiopia.
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DOI：
10.1371/journal.pgen.1003110
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Di Rienzo A
中科院分区：
文献类型：
--
作者：
Alkorta-Aranburu G;Beall CM;Witonsky DB;Gebremedhin A;Pritchard JK;Di Rienzo A
虽然缺氧是生理过程的主要压力，但一些人类在高海拔地区生存了数千年，表明他们已经适应了缺氧条件。这一假设最近得到了对西藏高原人的研究的证实，该研究表明，候选基因中的多态性显示了自然选择的特征以及血红蛋白水平变化的重复关联信号。我们将基因组分析扩展到两个埃塞俄比亚民族：阿姆哈拉族和奥罗莫族。对于每个种族群体，我们对低海拔和高海拔居民进行了抽样，从而可以在不同海拔和不同种族群体之间进行遗传和表型比较。通过使用Illumina阵列在这些样品中收集全基因组SNP基因型数据。我们发现，与藏族血红蛋白变异相关的变异或同一位点的其他变异不影响藏族的特征。然而，在阿姆哈拉人中，SNP rs10803083与全基因组显著水平的血红蛋白水平相关。在两个种族组中没有观察到氧饱和度水平的显著基因型关联。基于等位基因频率差异的方法没有检测到候选缺氧基因中的离群值，但高地人和低地人之间最分化的变体在病原体防御中具有明确的作用。有趣的是，一个显着过量的等位基因频率分歧一贯检测到参与细胞周期控制和DNA损伤和修复的基因，从而指出了新的途径，高海拔适应。最后，通过比较高地人和低地人之间的CpG甲基化水平，在奥罗莫人的个体基因中发现了几个显著的信号。虽然缺氧是生理过程的主要压力，但一些人类在高海拔地区生存了数千年，表明他们已经适应了缺氧条件。与这一想法相一致，以前的研究已经确定了西藏高原人与血红蛋白水平降低相关的遗传变异，这是高海拔地区的一种有利表型。为了比较高海拔适应的遗传基础，我们分别收集了生活在高海拔和低海拔的蒙古人的遗传和表观遗传数据。我们发现，与藏族血红蛋白变异相关的变异或同一位点的其他变异不影响藏族的特征。然而，我们发现了一种不同的变体，它与埃塞俄比亚人的血红蛋白水平显著相关。基于高地人和低地人之间等位基因频率差异的方法检测到基因中具有明显防御病原体作用的强烈信号，这与海拔之间病原体的已知差异一致。最后，我们发现了一些全基因组的显着表观遗传差异海拔。这些结果表明，埃塞俄比亚和西藏高原人通过不同的变异和遗传位点适应了相同的环境压力。
Although hypoxia is a major stress on physiological processes, several human populations have survived for millennia at high altitudes, suggesting that they have adapted to hypoxic conditions. This hypothesis was recently corroborated by studies of Tibetan highlanders, which showed that polymorphisms in candidate genes show signatures of natural selection as well as well-replicated association signals for variation in hemoglobin levels. We extended genomic analysis to two Ethiopian ethnic groups: Amhara and Oromo. For each ethnic group, we sampled low and high altitude residents, thus allowing genetic and phenotypic comparisons across altitudes and across ethnic groups. Genome-wide SNP genotype data were collected in these samples by using Illumina arrays. We find that variants associated with hemoglobin variation among Tibetans or other variants at the same loci do not influence the trait in Ethiopians. However, in the Amhara, SNP rs10803083 is associated with hemoglobin levels at genome-wide levels of significance. No significant genotype association was observed for oxygen saturation levels in either ethnic group. Approaches based on allele frequency divergence did not detect outliers in candidate hypoxia genes, but the most differentiated variants between high- and lowlanders have a clear role in pathogen defense. Interestingly, a significant excess of allele frequency divergence was consistently detected for genes involved in cell cycle control and DNA damage and repair, thus pointing to new pathways for high altitude adaptations. Finally, a comparison of CpG methylation levels between high- and lowlanders found several significant signals at individual genes in the Oromo. Although hypoxia is a major stress on physiological processes, several human populations have survived for millennia at high altitudes, suggesting that they have adapted to hypoxic conditions. Consistent with this idea, previous studies have identified genetic variants in Tibetan highlanders associated with reduction in hemoglobin levels, an advantageous phenotype at high altitude. To compare the genetic bases of adaptations to high altitude, we collected genetic and epigenetic data in Ethiopians living at high and low altitude, respectively. We find that variants associated with hemoglobin variation among Tibetans or other variants at the same loci do not influence the trait in Ethiopians. However, we find a different variant that is significantly associated with hemoglobin levels in Ethiopians. Approaches based on the difference in allele frequency between high- and lowlanders detected strong signals in genes with a clear role in defense from pathogens, consistent with known differences in pathogens between altitudes. Finally, we found a few genome-wide significant epigenetic differences between altitudes. These results taken together imply that Ethiopian and Tibetan highlanders adapted to the same environmental stress through different variants and genetic loci.
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DOI：
10.1073/pnas.1002443107
发表时间：
2010-06-22
影响因子：
11.1
作者：
Beall, Cynthia M.;Cavalleri, Gianpiero L.;Zheng, Yong Tang
通讯作者：
Zheng, Yong Tang
影响因子：
3.2
作者：
Alemu, Abebe;Muluye, Dagnachew;Gebeyaw, Melkamu
通讯作者：
Gebeyaw, Melkamu
影响因子：
9.8
作者：
Bersaglieri, T;Sabeti, PC;Hirschhorn, JN
通讯作者：
Hirschhorn, JN
影响因子：
2.6
作者：
Beall, CM
通讯作者：
Beall, CM
影响因子：
4.5
作者：
Bigham A;Bauchet M;Pinto D;Mao X;Akey JM;Mei R;Scherer SW;Julian CG;Wilson MJ;López Herráez D;Brutsaert T;Parra EJ;Moore LG;Shriver MD
通讯作者：
Shriver MD