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Genomic and Transcriptomic Examination of Functional Elements and Absent Sequences
Genomic and Transcriptomic Examination of Functional Elements and Absent Sequences
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152649
- ISBN
- 9798384075530
- DDC
- 575
- 서명/저자
- Genomic and Transcriptomic Examination of Functional Elements and Absent Sequences
- 발행사항
- [Sl] : University of California, San Francisco, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 134 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-03, Section: B.
- 주기사항
- Advisor: Li, Hao.
- 학위논문주기
- Thesis (Ph.D.)--University of California, San Francisco, 2024.
- 초록/해제
- 요약Background: Genome-wide association studies have identified numerous disease-associated variants, but a vast majority are located in non-coding regions, making it challenging to understand their functional impact. This complexity necessitates new techniques to identify causal variants in non-coding regions and elucidate their specific cellular contexts and mechanisms of action. Here we present work i) examining mutations that create nullomers in the human genome to explore its potential utility in identifying pathogenic mutations and ii) a single-cell multi-omic study identifying the transcriptome and regulome of the human and mouse hypothalamus to identify regulatory regions of obesity-associated variants.Methods: (i) We generated all possible mutations of the human genome that can lead to emergence of a nullomer, and examine where in the genome they emerge. (ii) We apply single-cell RNA and ATAC sequencing to adult hypothalamus samples.Results and Conclusions: (i) Our findings highlight CpG hypermutability and methylated cytosines as key elements leading to resurfacing of nullomers in individuals. We also showcase that nullomers can have applications in disease annotation and pathogenic variant identification. (ii) We identified regulatory elements of hypothalamus cell types and mapped obesity-associated variants to cell-type specific peaks. We validated these regions to be enhancers using CRISPR editing and CRISPRi.
- 일반주제명
- Genetics
- 일반주제명
- Bioinformatics
- 일반주제명
- Biology
- 일반주제명
- Molecular biology
- 키워드
- Gene regulation
- 키워드
- Genomics
- 키워드
- Hypothalamus
- 키워드
- Nullomers
- 기타저자
- University of California, San Francisco Biochemistry and Molecular Biology
- 기본자료저록
- Dissertations Abstracts International. 86-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798384075530
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a575
■1001 ▼aChan, Candace S. Y.▼0(orcid)0000-0001-9667-7996
■24510▼aGenomic and Transcriptomic Examination of Functional Elements and Absent Sequences
■260 ▼a[Sl]▼bUniversity of California, San Francisco▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a134 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-03, Section: B.
■500 ▼aAdvisor: Li, Hao.
■5021 ▼aThesis (Ph.D.)--University of California, San Francisco, 2024.
■520 ▼aBackground: Genome-wide association studies have identified numerous disease-associated variants, but a vast majority are located in non-coding regions, making it challenging to understand their functional impact. This complexity necessitates new techniques to identify causal variants in non-coding regions and elucidate their specific cellular contexts and mechanisms of action. Here we present work i) examining mutations that create nullomers in the human genome to explore its potential utility in identifying pathogenic mutations and ii) a single-cell multi-omic study identifying the transcriptome and regulome of the human and mouse hypothalamus to identify regulatory regions of obesity-associated variants.Methods: (i) We generated all possible mutations of the human genome that can lead to emergence of a nullomer, and examine where in the genome they emerge. (ii) We apply single-cell RNA and ATAC sequencing to adult hypothalamus samples.Results and Conclusions: (i) Our findings highlight CpG hypermutability and methylated cytosines as key elements leading to resurfacing of nullomers in individuals. We also showcase that nullomers can have applications in disease annotation and pathogenic variant identification. (ii) We identified regulatory elements of hypothalamus cell types and mapped obesity-associated variants to cell-type specific peaks. We validated these regions to be enhancers using CRISPR editing and CRISPRi.
■590 ▼aSchool code: 0034.
■650 4▼aGenetics
■650 4▼aBioinformatics
■650 4▼aBiology
■650 4▼aMolecular biology
■653 ▼aGene regulation
■653 ▼aGenomics
■653 ▼aHypothalamus
■653 ▼aNullomers
■653 ▼aTranscriptional regulatory elements
■690 ▼a0369
■690 ▼a0715
■690 ▼a0306
■690 ▼a0307
■71020▼aUniversity of California, San Francisco▼bBiochemistry and Molecular Biology.
■7730 ▼tDissertations Abstracts International▼g86-03B.
■790 ▼a0034
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17163293▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
