차세대 염기서열 및 단일염기다형성 데이터를 이용한 포유류의 유전체 변이와 유효집단크기 해독

학위논문 (박사)-- 서울대학교 대학원 : 농생명공학부, 2014. 8. 김희발.This doctoral dissertation consists of five studies related to mammalian genetic variation and effective population size using SNP data or NGS data. Effective population size is essential to measure data size, quality and genetic diversity of animal population. I thus investigated economic trait-associated genetic variation of domesticated animal using SNP data. In addition, I examined copy number variation related to domestication process of cattle using NGS data. In chapter 1, I introduced the basic background and necessity of the series of worked in this doctoral dissertation. The effective population size (Ne) is important to assess the genetic diversity of animal populations. In chapter 2, I characterized more accurate linkage disequilibrium in a sample of 96 dairy cattle producing milk in Korea and estimated Ne that is approximately 122. And I inferred historical Ne and I can knew that a rapid increase Ne over the past 10 generations, and increased slowly thereafter. These results can be rationalized using current knowledge of the history of the dairy cattle breeds producing milk in Korea. In chapter 3, I investigated the common minke whale (Balaenoptera acutorostrata) genome using next generation sequencing. After then, I estimated historical effective population size in the minke whale based on coalescent model to know when minke whale population size decreases rapidly. As a result, I guessed that minke whale population diversity downsized to approximately 3.1%. And strong predicted time of minke whale declination during Holocene is approximately between 194 and 902 years ago. These whole-genome sequencing offers a chance to better understand the population history of the largest aquatic mammals on earth. After knowing population characteristic, I investigated genetic variant related to economic traits of domesticated animal. In chapter 4, I identified SNPs related to horse racing performance. Thoroughbred, a relatively recent horse breed, is best known for its use in horse racing. Although myostatin (MSTN) variants have been reported to be highly associated with horse racing performance, the trait is more likely to be polygenic in nature. I conducted a two-stage genome-wide association study to search for genetic variants associated with the EBV. I identified 28 significant SNPs related to 17 genes. Among these, six genes have a function related to myogenesis and five genes are involved in muscle maintenance. To my knowledge, these genes are newly reported for the genetic association with racing performance of Thoroughbreds. It complements a recent horse GWAS of racing performance that identified other SNPs and genes as the most significant variants. These results will help to expand my knowledge of the polygenic nature of racing performance in Thoroughbreds. In chapter 5, I identified SNPs related to milk production of dairy cattle. Holsteins are known as the world's highest-milk producing dairy cattle. I inferred each EBVs using recent ridge regression BLUP. After then, I conducted multivariate genome-wide association study to search for genetic variants associated with the EBVs for milk production traits using SNP data. I identified 128 significant SNPs related to 47 genes. These genes were related to cellular component localization, protein localization, intracellular signaling cascade and microtubule. These genes are newly reported for the genetic association with milk production of Holstein. It complements a recent Holstein GWAS that identified other SNPs and genes as the most significant variants. These results will help to expand my knowledge of the polygenic nature of milk production in Holstein. Finally, I detected cattle copy number variations related to domestication process, as another genetic source except SNP. Copy number variation (CNV), a source of genetic diversity in mammals, has been shown to underlie biological functions related to production traits. Notwithstanding, there have been few studies conducted on CNVs using next generation sequencing at the population level. I used NGS data containing ten Holsteins, a dairy cattle, and 22 Hanwoo, a beef cattle. The sequence data for each of the 32 animals varied from 13.58-fold to almost 20-fold coverage. I detected a total of 6,811 deleted CNVs across the analyzed individuals (average length = 2,732.2 bp) corresponding to 0.74% of the cattle genome (18.6 Mbp of variable sequence). By examining the overlap between CNV deletion regions and genes, I selected 30 genes with the highest deletion scores. These genes were found to be related to the nervous system, more specifically with nervous transmission, neuron motion, and neurogenesis. I regarded these genes as having been effected by the domestication process. Further analysis of the CNV genotyping information revealed 94 putative selected CNVs and 954 breed-specific CNVs. This study provides useful information for assessing the impact of CNVs on cattle traits using NGS data at the population level.Abstract i Contents iv List of Tables vii List of Figures ix Abbreviation xv General Introduction 1 Chapter 1. Literature Review 8 1.1 Effective Population Size 9 1.2 Genome-wide Association Study 19 1.3 Copy Number Variation Using Next Generation Sequencing 27 Chapter 2. Accurate estimation of effective population size in the Korean dairy cattle based on linkage disequilibrium corrected by genomic relationship matrix 34 2.1 Abstract 35 2.2 Introduction 36 2.3 Materials and Methods 38 2.4 Results 48 2.5 Discussion 60 Chapter 3. Estimation of historical effective population size in the Minke whale based on coalescent model 65 3.1 Abstract 66 3.2 Introduction 67 3.3 Materials and Methods 68 3.4 Results 75 3.5 Discussion 80 Chapter 4. Multiple genes related to muscle identified through a joint analysis of a two-stage genome-wide association study for racing performance of 1,156 Thoroughbreds 82 4.1 Abstract 83 4.2 Introduction 84 4.3 Materials and Methods 86 4.4 Results 91 4.5 Discussion 116 Chapter 5. Multivariate GWAS of milk production traits using genomic estimated breeding value 122 5.1 Abstract 123 5.2 Introduction 124 5.3 Materials & Methods 127 5.4 Results 133 5.5 Discussion 149 Chapter 6. Deleted copy number variation of Hanwoo and Holstein using next generation sequencing at the population level 153 6.1 Abstract 154 6.2 Introduction 155 6.3 Materials & Methods 158 6.4 Results 169 6.5 Discussion 207 General Discussion 223 Reference 225 국문초록 250 감사의 글 253Docto

담시의 수용과 실험

학위논문(석사) --서울대학교 대학원 :영어영문학과(문학전공),2008. 8.Maste

契約의 成立에 關한 硏究 : 請約과 承諾을 중심으로

학위논문(석사)--서울대학교 대학원 :법학과,2004.Maste

경작토양으로부터 Carbofuran 분해 세균의 분리와 특성 규명

학위논문 (석사)-- 서울대학교 대학원 : 농생명공학부, 2011.2. 가종억.Maste

비강 및 부비동 반전성 유두종의 재발 및 발암원인으로 인간유두종바이러스 음성군에서 p53, p16의 발현에 관한 연구

Dept. of Medicine/석사[한글] [영문]Sinonasal inverted papillomas (SIPs) are recurrent and progressive unusual tumors of the nasal and paranasal sinus epithelium. Many reports have suggested human papilloma virus (HPV) infection is one of the causes of SIPs. However, the infection rates differ considerably among reporters, and pRb and p53 which are considered to interact with HPV viral genome were also affected in HPV-negative SIPs. p16 plays a critical role in the tumorigenesis of p16/cyclin D1/pRb pathway, and previous studies reported that p16 expression shows inverse relation with pRb which is usually inactivated due to HPV viral genome. Also, It has been reported that p53 shows reciprocal expression with HPV infection. However, p16 and p53 expressions according to disease courses such as recurrence or progression have not been studied along with HPV infection in SIPs. In this study, the clinical factors and representative proteins of cell cycle regulators, p16 and p53 were evaluated in patients with SIPs. HPV screening test were performed with 62 SIPs and they were sorted to control, recurrence and progression (to malignancy) groups. The semiquantitive scores for immunohistochemical stains of p16 and p53 (phosphorus and mutant form) and clinical factors such as sex, age, smoking history, operation methods, combined polyps, size of specimen, Krouse stage and time to recurrence and were compared between groups. The whole subjects were classified into four groups, p16+/p53-, p16-/p53-, p16+/p53+ and p16-/p53+, of which clinical factors also were compared. All SIPs showed HPV-negative, and endosopic surgery and advanced Krouse stage (p = 0.01 and p = 0.001, respectively) were associated with recurrence or progression. The p16 scored low (p = 0.004) and phosphorus and mutant forms of p53 (p = 0.001 and p = 0.014, respectively) scored highly in the recurrent or progression group significantly. There was difference of recurrence free survival (RFS) rate among alternative p16/p53 (phosphorus and mutant forms) groups significantly (p = 0.015 and p = 0.012, respectively), showing that the highest RFS rate was 82.4% in p16+/phosphorus form of p53- group and the lowest RFS rate was 33.3% in p16-/mutant form of p53+. In Kaplan-Meier analysis, the poorest disease courses were observed (p = 0.0003), demonstrating high possibility of recurrence in p16-/phosphorus form of p53+ group (p = 0.0009 vs p16-/mutant form of p53+ group).Thus, negativitiy of p16 and positivity of p53 might be related factors to poor clinical courses concerned with recurrence or progression and might be useful to predict disease course of HPV-negative SIPs at the first time of operation.ope

2017 탈석탄 친환경 에너지전환 국제 컨퍼런스(CNI세미나2017-140) (Alex Doukas,정구윤,안중기,Al Armendariz,Stefan Taschner,Li Jun,신동현)

- 개회사 : 충남연구원 강현수 원장 - 축사 : 산업통상자원부/환경부 장관, 충남 도의회 의장, 국회의원 - 특별연설 : 신 기후체제의 탈 석탄 전환 - 충남도지사 안희정 - 기조연설 : 세계에너지 전환의 흐름과 독일의 경험, 그리고 한국을 향한 제언 - Baerbel Hoehn - 발표1. 세계 탈석탄 동향과 금융투자 흐름 - Alex Doukas (미국) - 발표2. 발전회사 ENEL의 탈석탄 경험과 시사점 - 정구윤(이탈리아) - 사회 : 충남연구원 강현수 원장 - 발표1. 미세먼지 종합대책과 친환경 에너지 전환 - 안중기(환경부) - 발표2. 텍사스주 탈석탄 현황과 쟁점 - Al Armendariz(미국) - 발표3. 베를린 탈석탄 계획과 지방정부의 역할 - Stefan Taschner(독일) - 발표4. 허베이성 탈석탄 전략과 에너지 사용구조 개선 - Li Jun(중국) - 발표5. 충청남도 탈석탄 친환경 에너지전환을 위한 노력 - 신동헌(한국) - 사회 : 충청남도 기후에너지특별위원회 이유진 위원 - 좌장 : 대전세종연구원 박재묵 원장 - 세션2의 지방정부 발표자, 김홍장(당진시장), 손민우(그린피스), 여형범(충남연구원), 오동훈(한국중부발전) - 개회사 : 충남연구원 강현수 원장 - 축사 : 산업통상자원부/환경부 장관, 충남 도의회 의장, 국회의원 - 특별연설 : 신 기후체제의 탈 석탄 전환 - 충남도지사 안희정 - 기조연설 : 세계에너지 전환의 흐름과 독일의 경험, 그리고 한국을 향한 제언 - Baerbel Hoehn - 발표1. 세계 탈석탄 동향과 금융투자 흐름 - Alex Doukas (미국) - 발표2. 발전회사 ENEL의 탈석탄 경험과 시사점 - 정구윤(이탈리아) - 사회 : 충남연구원 강현수 원장 - 발표1. 미세먼지 종합대책과 친환경 에너지 전환 - 안중기(환경부) - 발표2. 텍사스주 탈석탄 현황과 쟁점 - Al Armendariz(미국) - 발표3. 베를린 탈석탄 계획과 지방정부의 역할 - Stefan Taschner(독일) - 발표4. 허베이성 탈석탄 전략과 에너지 사용구조 개선 - Li Jun(중국) - 발표5. 충청남도 탈석탄 친환경 에너지전환을 위한 노력 - 신동헌(한국) - 사회 : 충청남도 기후에너지특별위원회 이유진 위원 - 좌장 : 대전세종연구원 박재묵 원장 - 세션2의 지방정부 발표자, 김홍장(당진시장), 손민우(그린피스), 여형범(충남연구원), 오동훈(한국중부발전