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

New York University, New York NY

Investigators

Abstract

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.