DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Lee, Jeong Ho | - |
dc.contributor.advisor | 이정호 | - |
dc.contributor.author | Kim, Ja Hye | - |
dc.date.accessioned | 2022-04-21T19:33:35Z | - |
dc.date.available | 2022-04-21T19:33:35Z | - |
dc.date.issued | 2021 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=964721&flag=dissertation | en_US |
dc.identifier.uri | http://hdl.handle.net/10203/295590 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 의과학대학원, 2021.8,[iii, 57 p. :] | - |
dc.description.abstract | 1.49 variants per individual with average 6.17% of VAF in the early-stage vs 8.46 variants per individual with average 1.5% of VAF in the late-stage. Each of the early- and late-stage mutations has a distinct mutational signature compared to tumor-originated mutations. Regarding brain somatic mosaicism, I found that mutational signatures were specific to brain regions. Thus, this study provides new insight into somatic mutations arising in early and late developmental stages and their biological implication. Focal cortical dysplasia (FCD) is a cortical developmental malformation presenting intractable epilepsy, which is largely caused by somatic mutations that abnormally activate the mTOR pathway. This condition is the most cause of epileptic surgery in childhood. Even intensive diagnostic effort, many children with FCD type II remain without a molecular diagnosis. Then, in the part 2, I optimized the affected cell sorting system with subsequent bioinformatic analysis of whole genome sequencing. I was able to identify the causative mutations in 4 of 14 patients in genes encoding mTOR pathway components | - |
dc.description.abstract | Most somatic mutations arising during the normal development present at various levels in single or multiple tissues, depending on the developmental stage and the affected organs. However, it remains unclear how the human developmental stages or mutation-carrying organs affect somatic mutations’ features. In the first part, I performed a systemic and comprehensive analysis of low-level somatic mutations using deep whole-exome sequencing (average read depth ~500x) data in a total 498 of matched multiple tissues (e.g. brain, blood, and others) from 190 individuals. Interestingly, I found that the early-stage mutations (shared in multiple organs) showed significantly lower number but higher variant allele frequency (VAF), compared to the late-stage mutations (in a single organ) | - |
dc.description.abstract | 2 ultra-low-level somatic mutations and 2 germline structural variations. The cell sorting method and comprehensive bioinformatic algorithm is a great way to find the cause of the disease in patient without molecular diagnosis using conventional sequencing in FCDII. | - |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | Brain somatic mutations▼aWhole exome sequencing▼aMutation signature▼aFocal cortical dysplasia▼aWhole genome sequencing▼aCell isolation▼aUltra-low-level somatic mutation | - |
dc.subject | 뇌 체성 돌연변이▼a전장 엑솜 시퀀싱▼a돌연변이 시그니쳐▼a국소 피질 이형성증▼a전장 지놈 시퀀싱▼a세포 분리▼a초저빈도 체성 돌연변이 | - |
dc.title | Dissecting genomic landscape of somatic mutations in human brain | - |
dc.title.alternative | 인간 뇌 체성 돌연변이의 총괄적 분석 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 325007 | - |
dc.description.department | 한국과학기술원 :의과학대학원, | - |
dc.contributor.alternativeauthor | 김자혜 | - |
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