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• W3137010718 abstract "Author(s): Akbari, Ali | Advisor(s): Bafna, Vineet | Abstract: Adaptation is the central evolutionary process and is at the core of some of the greatest challenges facing humanity. HIV would likely cause nothing more than a harmless fever without the ability of the virus to adapt and eventually destroy the immune system. Cancer would be much more straightforward to treat if not for its ability to adapt to anti-cancer drugs. Malaria could be treated with cheap drugs such as Quinine instead of being one of the world's worst killers. In disease and health, we are in an arms race without fully understanding the rules of engagement. Humans have also adapted to live in harsh ecological niches, allowing them for example to digest milk sugars in adulthood, and to live at high altitudes with debilitating lack of Oxygen. Over 83 million people live at altitudes above 2,500 meters (8,200 ft) where the oxygen levels are 25% lower than at sea level. If not adapted, residing for a long time at such a harsh environment with low oxygen level can be fatal. One of the most striking example of high-altitude adaptation is the adaptation of Tibetan highlanders, where the favored genetic material is introgressed from archaic humans similar to Denisovans. Introgression is the introduction of genetic material into a population via interspecies mating. The complex pathways involved in hypoxia tolerance also inform upon our ability to understand ischemic diseases (stroke, cardiovascular diseases), and new molecular targets for these diseases. Therefore, this natural human experiment is a wonderful system to work with. When adaptation is genetic (inherited by offspring of adapted individuals), it leaves a variety of detectable signatures in genomes. Together with recent developments in DNA sequencing technologies in past decades, methods for detecting genomic regions under selection from population genomic data, have been actively developed. In contrast, little work has been done to identify the favored mutation in a selective sweep. Pinpointing the favored mutation among tens of thousands of other, hitchhiking, mutations is like a needle in a haystack problem.Identifying the favored mutation can provide a more precise picture of the origin of the selection; and allows people to do functional studies to improve the overall understanding of diseases. For example, adaptation to chronic hypoxia at high altitude can suggest targets for cardiovascular and other ischemic diseases. Also, identifying the favored mutation gives a high resolution picture revealing complicated evolutionary scenarios like multiple favored mutations and adaptive introgression.Here in this dissertation, we address the challenging but important problem of pinpointing the favored mutation in a selective sweep. We break the problem into smaller parts and very carefully craft them to accurately identify the favored mutation in a selective sweep, and also distinguish adaptively introgressed haplotypes from other models of selection." @default.
• W3137010718 created "2021-03-29" @default.
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• W3137010718 date "2018-01-01" @default.
• W3137010718 modified "2023-09-23" @default.
• W3137010718 title "Looking Into the Past: Identifying Genetic Mutations and Introgression Events that Shaped Human Adaptation" @default.
• W3137010718 hasPublicationYear "2018" @default.
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