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Investigating the FAIM2 Locus in Predisposition to Childhood Obesity
Investigating the FAIM2 Locus in Predisposition to Childhood Obesity
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211150935
- ISBN
- 9798382830766
- DDC
- 575
- 서명/저자
- Investigating the FAIM2 Locus in Predisposition to Childhood Obesity
- 발행사항
- [Sl] : University of Pennsylvania, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 138 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- 주기사항
- Advisor: Grant, Struan F. A.
- 학위논문주기
- Thesis (Ph.D.)--University of Pennsylvania, 2024.
- 초록/해제
- 요약The ch12q13 obesity locus is among the most significant childhood obesity loci identified in genome-wide association studies. This locus resides in a non-coding region within FAIM2; thus, the underlying causal variant(s) presumably influence disease susceptibility via an influence on cis-regulation within the genomic region. I implicated rs7132908 as a putative causal variant at this locus leveraging a combination of our inhouse 3D genomic data, public domain datasets, and several computational approaches. Using a luciferase reporter assay in human primary astrocytes, I observed allele-specific cis-regulatory activity of the immediate region harboring rs7132908. Motivated by this finding, I went on to generate isogenic human embryonic stem cell lines homozygous for either rs7132908 allele with CRISPR-Cas9 homology-directed repair to assess changes in gene expression due to genotype and chromatin accessibility throughout a differentiation to hypothalamic neurons, a key cell type known to regulate feeding behavior. I observed that the rs7132908 obesity risk allele influenced the expression of FAIM2 along with other genes, decreased the proportion of neurons produced during differentiation, up-regulated cell death gene sets, and conversely down-regulated neuron differentiation gene sets. I have therefore functionally validated rs7132908 as a causal obesity variant which temporally regulates nearby effector genes at the ch12q13 locus and influences neurodevelopment and survival.
- 일반주제명
- Genetics
- 일반주제명
- Neurosciences
- 일반주제명
- Bioinformatics
- 일반주제명
- Epidemiology
- 일반주제명
- Endocrinology
- 키워드
- Hypothalamus
- 키워드
- Obesity locus
- 키워드
- Risk variant
- 기타저자
- University of Pennsylvania Cell and Molecular Biology
- 기본자료저록
- Dissertations Abstracts International. 85-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798382830766
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a575
■1001 ▼aLittleton, Sheridan H.
■24510▼aInvestigating the FAIM2 Locus in Predisposition to Childhood Obesity
■260 ▼a[Sl]▼bUniversity of Pennsylvania▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a138 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-12, Section: B.
■500 ▼aAdvisor: Grant, Struan F. A.
■5021 ▼aThesis (Ph.D.)--University of Pennsylvania, 2024.
■520 ▼aThe ch12q13 obesity locus is among the most significant childhood obesity loci identified in genome-wide association studies. This locus resides in a non-coding region within FAIM2; thus, the underlying causal variant(s) presumably influence disease susceptibility via an influence on cis-regulation within the genomic region. I implicated rs7132908 as a putative causal variant at this locus leveraging a combination of our inhouse 3D genomic data, public domain datasets, and several computational approaches. Using a luciferase reporter assay in human primary astrocytes, I observed allele-specific cis-regulatory activity of the immediate region harboring rs7132908. Motivated by this finding, I went on to generate isogenic human embryonic stem cell lines homozygous for either rs7132908 allele with CRISPR-Cas9 homology-directed repair to assess changes in gene expression due to genotype and chromatin accessibility throughout a differentiation to hypothalamic neurons, a key cell type known to regulate feeding behavior. I observed that the rs7132908 obesity risk allele influenced the expression of FAIM2 along with other genes, decreased the proportion of neurons produced during differentiation, up-regulated cell death gene sets, and conversely down-regulated neuron differentiation gene sets. I have therefore functionally validated rs7132908 as a causal obesity variant which temporally regulates nearby effector genes at the ch12q13 locus and influences neurodevelopment and survival.
■590 ▼aSchool code: 0175.
■650 4▼aGenetics
■650 4▼aNeurosciences
■650 4▼aBioinformatics
■650 4▼aEpidemiology
■650 4▼aEndocrinology
■653 ▼aChildhood obesity
■653 ▼aGenome-wide association studies
■653 ▼aHypothalamus
■653 ▼aObesity locus
■653 ▼aRisk variant
■690 ▼a0369
■690 ▼a0317
■690 ▼a0766
■690 ▼a0409
■690 ▼a0715
■71020▼aUniversity of Pennsylvania▼bCell and Molecular Biology.
■7730 ▼tDissertations Abstracts International▼g85-12B.
■790 ▼a0175
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160215▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
