Eylem Seç
Evolutionary Genomics of Infectious Disease Across Spatial and Temporal Scales
Başlık:
Evolutionary Genomics of Infectious Disease Across Spatial and Temporal Scales
Yazar:
O'Neill, Mary B., author.
ISBN:
9780438159570
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (241 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: Caitlin S. Pepperell Committee members: Chris Hittinger; Christina Kendziorski; Bruce Klein; Bret Payseur.
Özet:
Adaptation leaves population level genetic signatures that can be detected with modern sequencing technologies. This thesis dissects genetic signatures in natural populations of humans and human pathogens to understand how infectious disease has shaped their evolution. At the level of an individual host, I characterize genome-wide patterns of diversity of Mycobacterium tuberculosis (M.tb) residing in individual tuberculosis (TB) patients and compare these to diversity in a global survey of the bacterium. I find that the diversity generated within an individual host varies dramatically, likely as a function of disease severity, and that lipids of the M.tb cell envelope appear to be subject to selection. Moving beyond the individual host, I characterize the geographic structure among extant M.tb and reconstruct the demographic and migration histories of each of the seven currently circulating lineages. Results illuminate the independent evolutionary trajectories of each lineage in shaping the global prevalence of TB, as well as the role of host populations' mobility in the spread of disease. Switching from pathogen genomes to those of humans, I investigate the evolutionary history and role of selection in shaping global patterns of allele frequencies at a locus associated with asthma and rhinovirus C susceptibility. I find that the 'protective' variant arose in anatomically modern humans prior to the out-of-Africa exodus and identify signatures of positive selection. However, observed patterns are not consistent with a classical selective sweep. Lastly, I use a disease mapping strategy guided by population genetic and functional genomic studies of human immune response variation, to identify genetic variants mediating variable susceptibility to a rare fungal infection in a genetically isolated population with increased prevalence of the disease. Of the regions identified, I highlight regulatory variants in the promoter region of IL6 and an adjacent long non-coding RNA as candidate susceptibility loci. Collectively these empirical studies demonstrate the power and value of computational analyses in understanding the evolutionary arms race between hosts and pathogens and in generating promising loci and hypotheses for future research.
Notlar:
School code: 0262
Tüzel Kişi Ek Girişi:
Mevcut:*
Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(687904.1) | 687904-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
On Order
Liste seç
Bunu varsayılan liste yap.
Öğeler başarıyla eklendi
Öğeler eklenirken hata oldu. Lütfen tekrar deneyiniz.
:
Select An Item
Data usage warning: You will receive one text message for each title you selected.
Standard text messaging rates apply.