Effects of recent evolution on the genetic basis of human disease [electronic resource]
- Erik Corona.
- Physical description
- 1 online resource.
- In the last 100,000 years, humans have been subjected to multiple different evolutionary pressures. Migration events, changing food sources, climate change, and technological advances are some of the ways environmental changes have applied pressure on human populations to undergo change. Recent advances in methods to measure differences in DNA sequences have led to new powerful techniques to measure the effect of evolution on different human populations. Also due to the availability of recent explosion of genomic data, our understanding of genetic basis of human disease has grown significantly. However, our knowledge regarding the effect that recent evolution has had on the genetic susceptibility to disease has grown to a much lesser extent. There is a lack of studies attempting to place the genetic basis of disease in the context of recent evolutionary changes. I describe multiple ways in which recent evolutionary pressures on the human genome can lead to insights to understanding how evolution has impacted complex disease. I show that GWAS (Genome-Wide Association Studies) are particularly well suited to measure the effect of recent evolution in complex disease. I provide methodology to detect positive selection in human disease and are able to ascertain whether recent evolution has disproportionately increased or decreased the risk of inherited disease. In addition, I introduce a method to approximate when and where genetic risk differentiation for specific disease has occurred, starting when humans began migration out of Africa. Environmental changes in the last 10,000 years known to have created novel, diverse, and pervasive pathogens. I provide methodology to find positive selection in communicable disease. I identify populations that have most likely been severely impacted by specific pathogens in recent human history. I develop and apply methods to identify specific genetic variants important to both communicable and inherited disease that have been affected by evolutionary pressures. I find that type 1 diabetes has recently undergone strong positive selection towards increasing genetic risk in European derived populations. In addition type 2 diabetes and pancreatic cancer is associated with migration trajectories and I find genetic risk differentiation exceeding what is expected by genetic drift in a total of 11 complex diseases. Finally, I find evidence of positive selection in many distinct populations within proteins interacting bacillus anthracis and yersinia pestis, which cause anthrax and the bubonic plague, respectively. I have shown how recent evolution can lead to an increased understanding of both inherited and infectious disease.
- Publication date
- Submitted to the Program in Biomedical Informatics.
- Thesis (Ph.D.)--Stanford University, 2012.