Doctoral Dissertation Improvement: Genetic Marker Bias Effects on Inferences of Human Evolutionary History

博士论文改进：遗传标记偏差对人类进化史推论的影响

• 批准号: 0622348
• 负责人: Todd Disotell
• 金额: --
• 依托单位: New York University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-15 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0622348&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Improvement; Genetic; Marker

Human beings carry evidence of much of their history as a species in patterns of DNA variation in their genomes. Anthropologists have used patterns of genetic variation in human populations to infer past human migrations and divergences between populations. Genetic data also have been used to distinguish between natural selection, human behavior, and random events, as influences on human evolution at the molecular level. However, patterns that are apparently indicative of evolutionary forces may instead be artifacts of biases towards the inclusion of particular types of genetic variants in a study. Biases can be introduced during the discovery of testable genetic variants or during the design of databases or gene chips. In this project, the researchers will examine the extent to which biases in the design of current public databases of human genetic variation (i.e. HapMap) and the latest tools for gathering genetic data (gene chips or microarrays) affect results of molecular anthropology studies. They ask whether or not pre-made gene chips and genetic databases widely used by the medical community for gene mapping are appropriate for inferring population history and human evolution, within what types of populations significant effects of bias would be expected, and the nature and consequences of such bias.As an example, this research will use predominantly Southeast Asian populations which were underrepresented in the original studies of the human genome and development of current gene mapping technologies. Saliva samples will be collected from individuals as a source of DNA from a minimum of four ethnic minorities (Akha, Lisu, Lahu, Hmong, or Karen), commonly referred to as Hill Tribes, residing in Northern Thailand. These populations are of interest because they are known to have complex migratory histories throughout Asia, and individuals are unlikely to marry outside of their ethnicity. DNA from other Asian and non-Asian majority populations is already available for use in this study. Genetic variation within and between each population will be measured, and this information will be compiled to create artificial simulated populations with which to test hypotheses, which will help the researchers to understand actual observations better. Results will then be analyzed for evidence of known kinds of evolutionary events for each group of genetic variants. Comparison of the results will show what types of biases have significant affects on such inferences, and allow for a more comprehensive genetic characterization of the populations under study.The broader impacts of this study include describing the extent to which the accuracy of scientists' views of human dispersal and population history may be affected by biases in widely-available genotyping tools and databases originally designed for gene mapping. This project will also facilitate international (Thailand and United States), interdisciplinary (Anthropology, Psychiatry, and Genetics), and institutional (New York University Graduate School of Arts and Sciences and Yale University School of Medicine) collaborations. Both samples and data collected for this study will be used for graduate student training of American and Thai researchers, with the intent to continue this international collaboration in the future.

人类的基因组中的 DNA 变异模式携带着其作为一个物种的大部分历史的证据。人类学家利用人类群体的遗传变异模式来推断过去的人类迁徙和群体之间的差异。 遗传数据还被用来区分自然选择、人类行为和随机事件，以在分子水平上影响人类进化。 然而，明显表明进化力量的模式可能是研究中包含特定类型遗传变异的偏见的产物。 在发现可测试的遗传变异期间或在设计数据库或基因芯片期间可能会引入偏差。 在这个项目中，研究人员将研究当前人类遗传变异公共数据库（即 HapMap）和收集遗传数据的最新工具（基因芯片或微阵列）设计中的偏差对分子人类学研究结果的影响程度。 他们询问医学界广泛用于基因图谱的预制基因芯片和遗传数据库是否适合推断人群历史和人类进化，在哪些类型的人群中预期会出现重大偏差影响，以及这种偏差的性质和后果。 例如，这项研究将主要使用东南亚人群，这些人群在人类基因组的原始研究和当前基因图谱技术的发展中代表性不足。 将从至少四个少数民族（阿卡族、傈僳族、拉祜族、苗族或克伦族）（通常被称为山地部落，居住在泰国北部）的个人中采集唾液样本作为 DNA 来源。 这些人群之所以引起人们的关注，是因为众所周知，他们在整个亚洲有着复杂的迁徙历史，而且个人不太可能与其他种族通婚。 来自其他亚洲和非亚洲大多数人群的 DNA 已可用于本研究。 每个种群内部和之间的遗传变异将被测量，这些信息将被编译以创建人工模拟种群来检验假设，这将有助于研究人员更好地理解实际观察结果。然后将对结果进行分析，以获取每组遗传变异的已知进化事件类型的证据。 结果的比较将显示哪些类型的偏差对此类推论有重大影响，并允许对所研究的种群进行更全面的遗传表征。这项研究的更广泛影响包括描述科学家对人类传播和种群历史的看法的准确性可能在多大程度上受到广泛使用的基因分型工具和最初为基因图谱设计的数据库中的偏差的影响。 该项目还将促进国际（泰国和美国）、跨学科（人类学、精神病学和遗传学）和机构（纽约大学艺术与科学研究生院和耶鲁大学医学院）合作。本研究收集的样本和数据将用于美国和泰国研究人员的研究生培训，以期在未来继续这项国际合作。