Genes and the fertility of Tibetan Women at High Altitude in Nepal

尼泊尔高海拔藏族妇女的基因与生育能力

• 批准号: 1153911
• 负责人: Cynthia Beall
• 金额: $ 39.62万
• 依托单位: Case Western Reserve University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1153911&HistoricalAwards=false
• 关键词: Genes; fertility; Tibetan; Women; Altitude

Tibetans have lived at altitudes above 3000m (~10,000') for at least 10,000 years and consequently have distinctive biological traits, including unexpectedly low levels of hemoglobin, the molecule that carries oxygen. Genes accounting for such hemoglobin levels were recently identified and occur at uniquely high frequency among Tibetans. The likely mechanism for this high frequency is higher fertility and child survival for those people with the low-hemoglobin forms of those genes. This research will test the hypothesis that Tibetan women at high altitude in Nepal with the low-hemoglobin variants of the genes have more surviving children than those with the other variants. 1350 women of Tibetan ethnicity residing at 3000m or higher who have completed their reproductive careers will provide DNA for typing the genes called EPAS1, EGLN1 and HIF1alpha that were previously found to regulate the response to hypoxia (low oxygen availability), such as that occurring at high altitudes. In addition, measurements of hemoglobin concentration and oxygen saturation of hemoglobin, as well as information on these women's fertility history and the survival of their children, will be collected. The predicted outcome is that women with the forms of the genes that are most frequent among Tibetans will have lower hemoglobin concentration, higher oxygen saturation of hemoglobin, and more surviving children. Those results will connect a severe environmental stress to biological and genetic variation and reproductive success, building a case for natural selection operating in a human population and improving our understanding of the processes of adapting to new environments. This U.S.-Nepalese collaborative research has health implications at all altitudes because these genes are necessary for intrauterine development, and they play central roles in the biology of diseases as diverse as osteo- and rheumatoid arthritis, heart failure, and cancer.

藏族人在海拔3000米(约10000英尺)以上生活了至少1万年，因此具有独特的生物学特征，包括出人意料的低水平血红蛋白，这种分子携带氧气。最近发现了导致这种血红蛋白水平的基因，并且这种基因在藏族中出现的频率非常高。这种高频率的可能机制是那些具有这些基因的低血红蛋白形式的人具有更高的生育率和儿童存活率。这项研究将检验这样一种假设，即在尼泊尔高海拔地区，携带低血红蛋白变异基因的藏族妇女比那些携带其他变异基因的藏族妇女有更多存活的孩子。1350名居住在海拔3000米或更高的藏族女性完成了她们的生殖生涯，她们将提供DNA，用于检测EPAS1、EGLN1和HIF1α基因，这些基因以前被发现调节对低氧(低氧可获得性)的反应，例如发生在高海拔地区的反应。此外，还将收集对血红蛋白浓度和血氧饱和度的测量，以及关于这些妇女的生育史及其子女存活率的信息。预测的结果是，拥有藏族中最常见的基因形式的女性将拥有较低的血红蛋白浓度，较高的血红蛋白氧饱和度，以及更多存活的孩子。这些结果将把严重的环境压力与生物和遗传变异以及生殖成功联系起来，为自然选择在人类群体中运作建立了理由，并提高了我们对适应新环境的过程的理解。这项美国和尼泊尔的合作研究对所有海拔地区的健康都有影响，因为这些基因是宫内发育所必需的，它们在骨性关节炎和类风湿性关节炎、心力衰竭和癌症等各种疾病的生物学中发挥着核心作用。