A genome-wide gene expression signature of environmental geography in leukocytes of Moroccan Amazighs.
A genome-wide gene expression signature of environmental geography in leukocytes of Moroccan Amazighs.
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DOI：
10.1371/journal.pgen.1000052
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发表时间：
2008-04-11
期刊：
影响因子：
4.5
通讯作者：
Gibson, Greg
中科院分区：
文献类型：
--
作者：
Idaghdour, Youssef;Storey, John D.;Jadallah, Sami J.;Gibson, Greg
人类经历的不同环境可能会影响生理和疾病易感性。为了估计环境对转录本丰度的影响程度，我们检测了 46 名沙漠游牧民族、山区农业民族和沿海城市摩洛哥阿马齐格人的外周血白细胞样本中的基因表达。尽管人类的表达异质性很大，但多达三分之一的白细胞转录组被发现与区域之间的差异有关。全基因组多态性分析表明，总样本中的遗传分化是有限的，不太可能解释表达差异。 1,505 个 CpG 位点的甲基化分析表明甲基化对观察到的基因表达差异的贡献有限。遗传网络分析进一步表明，免疫功能的特定方面受到区域因素的强烈影响，并可能影响对呼吸道疾病和炎症性疾病的易感性。我们的结果显示了区域人口差异的强大全基因组基因表达特征，这些差异可能包括生活方式、地理和生物因素，这意味着这些因素在调节人类基因表达变异方面至少可以发挥与遗传差异一样大的作用。糖尿病、哮喘、抑郁症等复杂疾病的发病率在许多国家几乎成为流行病，并且与生活方式的转变同时发生。显然，这是现代文化和环境因素与人类历史遗传遗产相互作用的结果。为了估计生活方式和地理等环境因素对基因表达的影响程度，我们检测了来自三个摩洛哥阿马齐格族群的外周血白细胞样本的基因表达差异，这三个族群有着不同的生活方式：沙漠游牧民族、山区农业民族和沿海城市民族。我们的数据显示，多达三分之一的白细胞转录组与这三个区域之间的差异相关。网络分析表明，免疫功能的特定方面受到区域因素的强烈影响，并可能影响疾病的易感性。三个区域之间的遗传和甲基化差异是有限的，不太可能解释观察到的基因表达差异的程度。从这项研究中获得的见解强调了从传统生活方式到现代生活方式的转变可能对人类疾病易感性产生的影响，并进一步证明需要将基因表达谱与遗传关联研究结合起来以预测疾病易感性。
The different environments that humans experience are likely to impact physiology and disease susceptibility. In order to estimate the magnitude of the impact of environment on transcript abundance, we examined gene expression in peripheral blood leukocyte samples from 46 desert nomadic, mountain agrarian and coastal urban Moroccan Amazigh individuals. Despite great expression heterogeneity in humans, as much as one third of the leukocyte transcriptome was found to be associated with differences among regions. Genome-wide polymorphism analysis indicates that genetic differentiation in the total sample is limited and is unlikely to explain the expression divergence. Methylation profiling of 1,505 CpG sites suggests limited contribution of methylation to the observed differences in gene expression. Genetic network analysis further implies that specific aspects of immune function are strongly affected by regional factors and may influence susceptibility to respiratory and inflammatory disease. Our results show a strong genome-wide gene expression signature of regional population differences that presumably include lifestyle, geography, and biotic factors, implying that these can play at least as great a role as genetic divergence in modulating gene expression variation in humans. The incidence of complex diseases such as diabetes, asthma, and depression is almost epidemic in many countries and coincides with transition in lifestyles. Clearly this is a result of interaction between modern cultural and environmental factors with the genetic legacy of human history. To estimate the extent of the effects of environmental factors, including lifestyle and geography, on gene expression, we examined gene expression differentiation in peripheral blood leukocyte samples from three Moroccan Amazigh groups leading distinct ways of life: desert nomadic, mountain agrarian and coastal urban. Our data shows that as much as one third of the leukocyte transcriptome is associated with differences among the three regions. Network analysis implies that specific aspects of immune function are strongly affected by regional factors and may influence disease susceptibility. Genetic and methylation differentiation between the three regions is limited and is unlikely to explain the extent of the observed gene expression differentiation. Insight gained from this study highlights the impact transitions from traditional to modern lifestyles likely have on human disease susceptibility and further warrant the need to incorporate gene expression profiling alongside genetic association studies for the prediction of disease susceptibility.
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