Characterizing the Natural Genetic and Epigenetic Diversity of Human Populations

• NCJ Number: 309935
• Author(s): Shyamalika Gopalan
• Date Published: 2019
• Length: 176 pages
• Grant Number(s): 2016-DN-BX-0011
• Agencies: NIJ-Sponsored
• Publication Type: Thesis/Dissertation; Research (Applied/Empirical)
• Award: Developing forensic epigenomic age-estimation tools for diverse populations

Annotation

This dissertation research characterizes the natural genetic and epigenetic diversity of human populations.

Abstract

This study analyzes genome-wide patterns of change in DNA methylation with increasing age in sub-Saharan Africans and shows that certain sites in the genome can serve as accurate biomarkers of chronological age, even across highly diverse human populations. This dissertation presents several projects that together link topics at the forefront of human genetics today, from epigenetics to ancient DNA to the increased inclusion of natural genetic diversity. This research also identifies genetic variants that may influence baseline levels of DNA methylation at certain age-associated sites in the genome. The author characterizes patterns of DNA methylation and age in human bone in order to develop the first statistical method of estimating age from skeletal remains for forensic purposes. To this end, the researcher generated a dataset of genome-wide DNA methylation from bone samples collected from body donation programs and leveraged existing bone datasets, derived from living donors, to statistically identify strong biomarkers of age in this tissue type. In this dissertation, the researcher also analyze genetic data from the Chabu, a population of isolated hunter-gatherers from southwest Ethiopia, to understand their recent demographic history. By integrating genetic data from across eastern Africa, the author shows that the Chabu are genetically distinct from all nearby populations and show a genetic affinity to an ancient individual who predated the arrival of agriculture to this region. The results suggest that the Chabu are direct descendants of earlier populations of local hunter-gatherers. The researcher also show that the Chabu have experienced a precipitous decline in effective population size (Ne) over the past 50 generations, mirroring the demographic history of other hunter-gatherer populations in eastern Africa. Finally, the researcher also reviews the extensive literature surrounding archaic introgression and ancient DNA for a non-specialist audience.