서브메뉴
검색
Exploring Plasmodium falciparum Genetic Diversity to Understand Malaria Immunity and Infection Risk
Exploring Plasmodium falciparum Genetic Diversity to Understand Malaria Immunity and Infection Risk
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151319
- ISBN
- 9798382783420
- DDC
- 591
- 서명/저자
- Exploring Plasmodium falciparum Genetic Diversity to Understand Malaria Immunity and Infection Risk
- 발행사항
- [Sl] : Harvard University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 229 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- 주기사항
- Advisor: Neafsey, Daniel E.
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2024.
- 초록/해제
- 요약Plasmodium parasites, the causative agents of malaria, have a complex evolutionary history involving their arthropod vectors, vertebrate hosts, and environment. Plasmodium falciparum is the deadliest of these malaria parasites, causing the deaths of hundreds of thousands of humans each year. In malaria-endemic settings, humans do not develop sterilizing immunity to P. falciparum infection; instead, naturally acquired immunity (NAI) against symptomatic or severe disease builds with repeated exposure.Most of the P. falciparum genome is not diverse, except for small regions within antigens with extremely high diversity. For this diversity to be maintained in parasite populations, it must offer some level of fitness advantage. These pockets of diversity are thought to be the result of diversifying selection imposed by the human immune system, but it is less understood how the acquisition of immunity relies upon or interacts with these antigenic regions. In this work, we explore the diversity of P. falciparum parasites in natural infections within a longitudinal cohort, seeking to understand how parasite genetic diversity may reflect natural immunity.In Chapter 1, we review the current state of genomic surveillance for P. falciparum, as well as what is known about naturally acquired immunity and infection risk. In Chapter 2, we develop two methods for studying genetic diversity within P. falciparum. We compare these to other targeted sequencing methods and evaluate the best methods for a variety of use cases, including studies of relatedness, complexity of infection, and geographic attribution.In Chapter 3, we begin to explore genetic data that we generated from a longitudinal cohort from malaria-endemic Mali. We search these data for potential genetic signals of naturally acquired immunity, including natural infection duration, asymptomatic period length, and complexity of infection. In Chapter 4, we determine the molecular force of infection for each individual over the years of the longitudinal study. We then use those data to evaluate the heterogeneity of infection risk and explore potential contributors to this heterogeneity.Finally, in Chapter 5, we explore these findings in the broader context of malaria genomics and public health. We consider the potential limitations of this work, as well as explore potential next steps for these questions.
- 일반주제명
- Parasitology
- 일반주제명
- Bioinformatics
- 일반주제명
- Genetics
- 일반주제명
- Epidemiology
- 일반주제명
- Immunology
- 키워드
- Genomics
- 키워드
- Immunity
- 키워드
- Infection risk
- 키워드
- Malaria
- 기타저자
- Harvard University Medical Sciences
- 기본자료저록
- Dissertations Abstracts International. 85-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008250123s2024 us c eng d■001000017161168
■00520250211151319
■006m o d
■007cr#unu||||||||
■020 ▼a9798382783420
■035 ▼a(MiAaPQ)AAI31239028
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a591
■1001 ▼aLaVerriere, Emily.▼0(orcid)0000-0002-4750-4199
■24510▼aExploring Plasmodium falciparum Genetic Diversity to Understand Malaria Immunity and Infection Risk
■260 ▼a[Sl]▼bHarvard University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a229 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-12, Section: B.
■500 ▼aAdvisor: Neafsey, Daniel E.
■5021 ▼aThesis (Ph.D.)--Harvard University, 2024.
■520 ▼aPlasmodium parasites, the causative agents of malaria, have a complex evolutionary history involving their arthropod vectors, vertebrate hosts, and environment. Plasmodium falciparum is the deadliest of these malaria parasites, causing the deaths of hundreds of thousands of humans each year. In malaria-endemic settings, humans do not develop sterilizing immunity to P. falciparum infection; instead, naturally acquired immunity (NAI) against symptomatic or severe disease builds with repeated exposure.Most of the P. falciparum genome is not diverse, except for small regions within antigens with extremely high diversity. For this diversity to be maintained in parasite populations, it must offer some level of fitness advantage. These pockets of diversity are thought to be the result of diversifying selection imposed by the human immune system, but it is less understood how the acquisition of immunity relies upon or interacts with these antigenic regions. In this work, we explore the diversity of P. falciparum parasites in natural infections within a longitudinal cohort, seeking to understand how parasite genetic diversity may reflect natural immunity.In Chapter 1, we review the current state of genomic surveillance for P. falciparum, as well as what is known about naturally acquired immunity and infection risk. In Chapter 2, we develop two methods for studying genetic diversity within P. falciparum. We compare these to other targeted sequencing methods and evaluate the best methods for a variety of use cases, including studies of relatedness, complexity of infection, and geographic attribution.In Chapter 3, we begin to explore genetic data that we generated from a longitudinal cohort from malaria-endemic Mali. We search these data for potential genetic signals of naturally acquired immunity, including natural infection duration, asymptomatic period length, and complexity of infection. In Chapter 4, we determine the molecular force of infection for each individual over the years of the longitudinal study. We then use those data to evaluate the heterogeneity of infection risk and explore potential contributors to this heterogeneity.Finally, in Chapter 5, we explore these findings in the broader context of malaria genomics and public health. We consider the potential limitations of this work, as well as explore potential next steps for these questions.
■590 ▼aSchool code: 0084.
■650 4▼aParasitology
■650 4▼aBioinformatics
■650 4▼aGenetics
■650 4▼aEpidemiology
■650 4▼aImmunology
■653 ▼aGenomics
■653 ▼aImmunity
■653 ▼aInfection risk
■653 ▼aMalaria
■653 ▼aPlasmodium falciparum
■690 ▼a0718
■690 ▼a0715
■690 ▼a0369
■690 ▼a0982
■690 ▼a0766
■71020▼aHarvard University▼bMedical Sciences.
■7730 ▼tDissertations Abstracts International▼g85-12B.
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17161168▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
