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.

人类在其基因组中具有DNA变异模式的物种的大部分历史证据。人类学家使用人群中遗传变异的模式来推断过去的人类迁移和人群之间的分歧。 遗传数据也已被用来区分自然选择，人类行为和随机事件，因为在分子水平上对人类进化的影响。 但是，显然表明进化力的模式可能是偏见属于在研究中纳入特定类型的遗传变异的伪像。 在发现可测试遗传变异的过程中或在数据库或基因芯片的设计期间可以引入偏差。 在该项目中，研究人员将研究当前人类遗传变异（即HAPMAP）的公共数据库设计中偏见的程度，以及收集遗传数据（基因芯片或微阵列）的最新工具会影响分子人类学研究的结果。 他们询问医学界广泛使用的基因芯片和遗传数据库是否适用于推断人口历史和人类进化，在哪种类型的人群中，预期的偏见会产生重大影响，以及此类BIA的性质和后果。例如，这项研究将使用这项研究主要是在基因和基因研究中，这些研究主要是在基因中的发展，并且是基因的发展。 唾液样本将从个体中收集，作为至少四个少数民族（Akha，Lisu，Lahu，Hmong或Karen）的DNA来源，通常称为居住在泰国北部的Hill Tribes。 这些人群引起了人们的关注，因为他们在整个亚洲都有复杂的迁徙历史，并且个人不太可能在其种族之外结婚。 来自亚洲和非亚洲多数人群的DNA已经可用于本研究。 将测量每个人群内部和之间的遗传变异，并将汇编这些信息以创建人工模拟人群来检验假设，这将帮助研究人员更好地理解实际观察结果。然后，将分析结果，以获取每组遗传变异的已知进化事件的证据。 结果的比较将显示哪些类型的偏见对这种推论产生了重大影响，并允许对研究人群的更全面的遗传表征。这项研究的更广泛的影响包括描述科学家对人类分散和人口历史的准确性可能在多大程度上受到偏见的影响，以广泛的基因型工具和数据量为基因构成基因构成基因型的偏见。 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）以及机构（纽约大学艺术与科学研究生学院和耶鲁大学医学学院）合作。为这项研究收集的样本和数据都将用于美国和泰国研究人员的研究生培训，并打算将来继续这一国际合作。