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Selective Whole Genome Amplification (SWGA) Reveals Population Genomics of Leishmania braziliensis Directly from Patient Skin Biopsies / Olivia A Pilling.
Dissertations & Theses @ University of Pennsylvania Available online
Dissertations & Theses @ University of Pennsylvania- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Pilling, Olivia A., author.
- Language:
- English
- Subjects (All):
- Parasitology.
- Genetics.
- Dermatology.
- Oncology.
- Cell and Molecular Biology--Penn dissertations.
- Penn dissertations--Cell and Molecular Biology.
- Local Subjects:
- Parasitology.
- Genetics.
- Dermatology.
- Oncology.
- Cell and Molecular Biology--Penn dissertations.
- Penn dissertations--Cell and Molecular Biology.
- Physical Description:
- 1 online resource (178 pages)
- Contained In:
- Dissertations Abstracts International 85-12B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania, 2022.
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- Language Note:
- English
- Summary:
- In Brazil, Leishmania braziliensis is the main causative agent of cutaneous leishmaniasis (CL), a neglected tropical disease. CL manifests with varying degrees of severity often with high rates of treatment failure. Understanding the parasite factors that contribute to disease presentation and treatment outcome remains a challenge due to difficulties in isolating and culturing parasites from patient lesions. Here we present the development of selective whole genome amplification (SWGA) for Leishmania and demonstrate that this method enables culture-independent analysis of parasite genomes obtained directly from primary patient skin samples. SWGA proves versatile across various Leishmania species found in different host species, which suggests that this method can be applied to both experimental infection models and clinical studies. Analysis of skin biopsies collected from patients in Corte de Pedra, Bahia, Brazil, showed extensive parasite genomic diversity. Integration of SWGA data with published whole genome data from cultured parasite isolates identified region-specific variants in Northeast Brazil, where treatment failure rates are notably high. We also compared parasite genomes from patients that cured and failed treatment and found unique variants associated with treatment failure. While there is no single variant or closely spaced variants specific to treatment outcome, a potential hotspot region linked to treatment failure emerged. SWGA offers a straightforward method to generate Leishmania genomes directly from patient samples, unlocking opportunities to explore the parasite's population genomics and its association with clinical phenotypes in the host.
- Notes:
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- Advisors: Beiting, Daniel P.; Committee members: Odom John, Audrey R.; Bittinger, Kyle; Brisson, Dustin; Moncla, Louise H.; Scott, Phillip.
- Department: Cell and Molecular Biology.
- Ph.D. University of Pennsylvania 2024.
- Local Notes:
- School code: 0175
- ISBN:
- 9798382835945
- Access Restriction:
- Restricted for use by site license.
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