Coming dissertations at Uppsala university
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Investigating African population structure using genomes and proteomes
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-537831
Modern humans originated in Africa and this continent is home to the highest genetic diversity in the world. Despite this, Africa remains an understudied region. In this thesis, I use genetic and proteomic data to unravel the demographic history of modern humans in Africa. By employing various methods on different data types, I explore both broad genetic patterns, as well as fine-scale structure in African populations. In Paper I, I focus on the methodological aspects of researching maternal histories in sub-Saharan Africa. I explore mitochondrial haplogroup assignment in African populations when genome-wide SNP array data is available and conclude that mitochondrial haplogroup frequencies inferred from most common SNP arrays used for human population analysis should be considered with caution. In Paper II, I developed a long-range sequence assay to amplify full-sequence mitochondrial genomes and used this novel method to generate complete mitogenomes from underrepresented regions in Africa. Combined with published mitogenomes, these data provide an overview of African mitochondrial haplogroups and give insights into the maternal background of the African continent. By analyzing female effective population sizes over time, I discovered that two population expansions happened earlier than previously thought. In the next paper, Paper III, I utilized target enrichment to sequence portions of the Y chromosome from sub-Saharan African men. This study gives an overview of the paternal lineages of the studied populations and identifies three types of geographical distributions across the Y haplogroups in our dataset. As DNA preservation and survival are limited, I shift the focus from DNA to proteins in Paper IV. I explored the use of proteomics in ancient individuals to decipher deep population structure in Africa by investigating the potential differences in protein sequences between the two groups representing the deepest population divergence in the tree of all modern humans. I identify amino acid variation between Southern African hunter-gatherer Khoe-San groups on the one hand, and the rest of humanity on the other hand and show that these amino acids can be investigated in ancient individuals from Africa. In Paper V, I investigate the demographic histories of one population specifically; the South African Coloured (SAC), the most admixed population of South Africa. Using genotype data from these individuals, I identify geographical differences in ancestry proportions and sex-biased admixture in the SAC. Taken altogether, my work has deepened our understanding of continental and regional genetic structure in African populations.
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Epigenetic Insights into the Impact of Endocrine Disruptors on (Neuro)phenotype - From Developmental to Multigenerational Effects
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-537437
Anthropogenic chemicals are pervasive in the environment, posing significant challenges due to their potential effects on human and wildlife health. Among these, endocrine disrupting chemicals (EDCs) are particularly concerning, as developmental exposure to EDCs has been linked to adverse outcomes later in life and across generations. Epigenetic mechanisms, which are crucial for embryonic development and play a key role in cell specification and the determination of phenotypic traits, may provide insights into how EDCs exert long-term effects. This thesis explores the connection between real-life developmental exposure to EDCs and epigenetic alterations, with a particular focus on neuro-phenotypical effects.
A previous epidemiological study demonstrated an association between prenatal co-exposure to eight EDCs (referred to as Mixture N1) and language delay in children, suggesting an impact of this mixture on neurodevelopment. Further research showed that in utero exposure to Mixture N1 altered gene expression and behavior in adult mice. In this study, the potential role of epigenetic mechanisms underlying these long-term effects was investigated by analyzing DNA methylation. Mixture N1 decreased DNA methylation in males at three genes associated with the hypothalamus-pituitary-adrenal (HPA) axis: glucocorticoid receptor (Nr3c1), mineralocorticoid receptor (Nr3c2), and corticotropin-releasing hormone receptor 1 (Crhr1). The decrease in Nr3c1 methylation was correlated with increased gene expression and with behavioral alterations. However, in vitro experiments did not provide evidence that Mixture N1 induced these epigenetic alterations during development.
This thesis also explored multi-generational effects of exposure to perfluorooctanesulfonic acid (PFOS) and perfluorobutanesulfonic acid (PFBS), two environmental pollutants with endocrine-disrupting properties. Zebrafish were exposed to chemicals during development at environmentally relevant concentrations. The exposure led to changes in behaviors, transcriptome, and DNA methylation, with significant DNA methylation changes observed in neuro-related genes. These alterations were also detected in their offspring (F1) and extended to the subsequent generation (F2). The investigation then focused on the potential mechanisms behind these transgenerational effects. Changes in RNA levels and RNA methylation, specifically m6A, were analyzed during early development in F2. PFOS was selected for this analysis due to its higher impact on neuro-phenotypical alterations. It was found that transcript levels and m6A patterns were altered in F2. These changes were associated with genes involved in epigenetic processes and translation, suggesting a possible role in the inheritance of neuro-phenotypical traits.
Overall, this thesis offers new insights into the connections between real-life exposure to EDCs, their impact on neuro-phenotypes, and the potential underlying epigenetic mechanisms.
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Essays on Environmental and Monetary Policy
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-537897
Essay I: This paper examines the impact of environmental policy in the form of emissions trading on income inequality in an endogenous growth model, an area that has received less attention thus far. We integrate pollution and environmental policy into a Schumpeterian growth framework to establish a theoretical relationship between the stringency of environmental policy and income inequality. Our analysis reveals that the nexus varies depending on the elasticity of labor supply. Specifically, a stricter environmental policy in the form of a lower cap for pollution permits increases income inequality when labor supply is inelastic. In the case of elastic labor supply, the relationship between environmental policy and income inequality becomes more involved and depends on parameter values. We show that a stricter environmental policy decreases income inequality under a reasonable calibration.
Essay II: This study incorporates pollution and environmental policy into an endogenous growth framework to evaluate the impact of environmental policy in the form of emissions trading on the economic takeoff of an economy. We find that a stricter environmental policy with a lower cap for pollution permits delays industrialization and decreases the economic growth rate along the transition path, but it does not affect long-run economic growth. Finally, we calibrate the model to current underdeveloped countries to examine whether the trade-off between environmental preservation and early industrialization is substantial for these countries. Due to their sufficiently high population growth, underdeveloped countries can safeguard the environment, notwithstanding a mere delay of a few years in the industrialization process.
Essay III (with Hanfeng Chen and Matthias Hänsel): Interest rates on new central bank digital currencies (CBDCs) can be expected to enter the monetary policy toolkit soon. Using an extended Sidrauski (1967) model featuring an oligopsonistic banking sector, we study the complex transmission of interest rates on CBDC, which generally involves both direct and indirect effects. This is because a CBDC rate cut not only affects the rate on the CBDC itself, but also induces non-competitive deposit providers to adjust their spreads, as the new substitute for their products becomes relatively less attractive. A calibration exercise suggests that the indirect effects depend strongly on the sources of deposit market power: If driven by high concentration, they substantially amplify the aggregate effects of the CBDC policy rate, both in response to transitory shocks as well as regarding its long-run welfare effects.