Download 제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회

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제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회
-행사명: 제3회 한국분자세포생물학회 이동성 유전인자 분과 학술대회
-행사 주제: Frontiers in Mobile Genetic Elements
-일시: 2013년 6월 28일(금), 13:00-18:00
-장소: 부산대학교 생물관 103호 세미나실
-참가방법 및 참가비: 현장참여/무료
-PROGRAM
13:00-13:10 : 등 록
13:10-13:20 : 환영인사 (김남수 교수, 이동성 유전인자 분과 회장)
Part I
13:20–15:00 Chair: 한복기 유전체센터장 (국립보건연구원)
13:20-13:40 안상중 박사 (국립수산과학원)
: MMTS, a new subfamily of Tc1-like transposons
13:40-14:00 이주미 박사 (동남권원자력의학원)
: Radiation effect on the cancer genome: DNA hypomethylation to genome instability
14:00-14:20 김대수 박사 (한국생명공학연구원)
: in silico Analysis of Transposable Elements in Cancer Associated Human Expressed
Sequences
14:20-14:40 허재원 박사 (국가영장류센터)
: Large-scale transcriptome sequencing and gene analyses in the crab-eating
macaque (Macaca fascicularis) for biomedical research
14:40-15:00 홍경원 박사 (국립보건연구원)
: Genome-wide studies of type 2 diabetes and the association with mobile genetic
elements
15:00-15:30 : Coffee Break, Group Photo
Young Scientist Presentation
15:30-16:00 Chair: 김희수 교수 (부산대학교 생명과학과)
15:30-15:40 정이든 (부산대학교 생명과학과)
: DNA methylation of transposable element links alternative splicing in CHM gene
15:40-15:50 문세영 (단국대학교 나노바이오의과학과)
: Evolutionary Fate of Species-Specific Endogenous Retroviruses (ERVs) in the Human
and Chimpanzee Lineages
15:50-16:00 이 재 (단국대학교 나노바이오의과학과)
: Identification of Human-specific AluS elements through comparing with other nonhuman primates
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제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회
Part II
16:00–17:00 Chair: 김남수 교수 (강원대학교 의생명과학과)
16:00-16:20 최익영 박사 (서울대학교, NICEM)
: Applications of NGS to Understand Genome Biology
16:20-16:40 진한준 박사 (단국대학교)
: Dissecting the genetic structure of Korean population using genome-wide SNP
arrays.
16:40-17:00 안 궁 박사 (테라젠이텍스)
: Comprehensive genome- and transcriptome-wide analyses of mutations associated
with microsatellite instability in Korean gastric cancers
17:00-17:30 Open Discussion
김남수 교수 (강원대학교), 김희수 교수 (부산대학교)
진한준 교수 (단국대학교), 한규동 교수 (단국대학교)
홍경원 박사 (국립보건연구원), 안상중 박사 (국립수산과학원),
김대수 박사 (한국생명공학연구원), 안 궁 박사 (테라젠이텍스)
이주미 박사 (동남권원자력의학원), 허재원 박사 (국가영장류센터)
17:30-20:00 Closing & Dinner
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제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회
MMTS, a new subfamily of Tc1-like transposons
Sang Jung Ahn1 and Hyung Ho Lee2
2
1 National Fisheries Research & Development Institute, Busan 619-902, Korea
Department of Biotechnology, Pukyong National University, Busan 608-737, Korea
A novel Tc1-like transposable element has been identified as a new DNA transposon in the
mud loach, Misgurnus mizolepis. The M. mizolepis Tc1-like transposon (MMTS) is comprised of
inverted terminal repeats and a single gene that codes Tc1-like transposase. The deduced amino acid
sequence of the transposase-encoding region of MMTS transposon contains motifs including DDE
motif, which was previously recognized in other Tc1-like transposons. However, putative MMTS
transposase has only 34-37% identity with well-known Tc1, PPTN, and S elements at the amino acid
level. In dot-hybridization analysis used to measure the copy numbers of the MMTS transposon in
genomes of the mud loach, it was shown that the MMTS transposon is present at about 3.36 x 104
copies per 2 x 109 bp, and accounts for approximately 0.027% of the mud loach genome. Here, we
also describe novel MMTS-like transposons from the genomes of carp-like fishes, flatfish species, and
cichlid fishes, which bear conserved inverted repeats flanking an apparently intact transposase gene.
Additionally, BLAST searches and phylogenetic analysis indicated that MMTS-like transposons
evolved uniquely in fishes, and comprise a new subfamily of Tc1-like transposons, with only modest
similarity to Drosophila melanogaster (foldback elements FB4, HB2 and HB1), Xenopus laevis,
Xenopus tropicalis, and Anopheles gambiae (Frisky).
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제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회
Radiation effect on the cancer genome: DNA hypomethylation
to genome instability
Joo Mi Yi
Research Institute, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan, South Korea
Ionizing radiation (IR) effects to genomic instability, which cause chromosomal aberrations,
deletions, insertions, and point mutations, is considered to be the precursor of tumorigenesis. Even
though effects on radiation exposure in cancer is very well-characterized by numbers of researchers,
the underlying epigenetic mechanism that drive alterations, especially site-specific changes in DNA
methylation patterns, remain elusive. Two types of epigenetic abnormalities, hypomethylation and
hypermethylation, are associates with cancer. Genomic hypermethylation in cancer has been observed
most often in CpG islands in gene’s promoter region. In contrast, hypomethylation in cancer is seen in
both highly and moderately mobile genetic elements such as DNA repeats, dispersed retrotransposons,
and endogenous retroviral elements. Growing evidence indicates that mobile genetic elements may
participate in the cancer progression and contribute to cancer initiating with hypomethylation in caner
genome. Here we focus on DNA methylation pattern change of mobile genetic elements in cancer
affected by IR and this could be involved in global hypomethylation and eventually contributed to
genome instability.
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제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회
in silico Analysis of Transposable Elements in Cancer Associated Human
Expressed Sequences
Dae-Soo Kim
Genome Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 111 Gwahangno,
Yuseong-gu, Daejeon 305-806, Republic of Korea
Transposable elements are the most abundant interspersed sequences in human genome. It has
been estimated that approximately 45% of the human genome comprises of transposable elements.
Recent studies have shown that transposable elements could affect coding sequences, splicing patterns,
and transcriptional regulation of human genes. In the present study, we investigated the transposable
elements in relation to human cancer. Our analysis pipeline adopted for screening methods of the
cancer specific expression from human expressed sequences. We developed a database for
understanding the mechanism of cancer development in relation to transposable elements. Totally, 999
genes were identified to be integrated in their mRNA sequences by transposable element. We believe
that our work might help many scientists who interested in cancer research to gain the insight of
transposable element for understanding the human cancer.
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제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회
Large-scale transcriptome sequencing and gene analyses in the crab-eating
macaque (Macaca fascicularis) for biomedical research
Jae-Won Huh
National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Ochang,
Chungbuk 363-883, Republic of Korea.
As a human replacement, the crab-eating macaque (Macaca fascicularis) is an invaluable nonhuman primate model for biomedical research, but the lack of genetic information on this primate has
represented a significant obstacle for its broader use. Here, we sequenced the transcriptome of 16
tissues originated from two individuals of crab-eating macaque (male and female), and identified
genes to resolve the main obstacles for understanding the biological response of the crab-eating
macaque. From 4 million reads with 1.4 billion base sequences, 31,786 isotigs containing genes
similar to those of humans, 12,672 novel isotigs, and 348,160 singletons were identified using the GS
FLX sequencing method. Approximately 86% of human genes were represented among the genes
sequenced in this study. Additionally, 175 tissue-specific transcripts were identified, 81 of which were
experimentally validated. In total, 4,314 alternative splicing (AS) events were identified and analyzed.
Intriguingly, 10.4% of AS events were associated with transposable element (TE) insertions. Finally,
investigation of TE exonization events and evolutionary analysis were conducted, revealing
interesting phenomena of human-specific amplified trends in TE exonization events. This report
represents the first large-scale transcriptome sequencing and genetic analyses of M. fascicularis and
could contribute to its utility for biomedical research and basic biology.
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제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회
Genome-wide studies of type 2 diabetes and the association
with mobile genetic elements
Kyung-Won Hong
Korea Center for Disease Control and Prevention Korea National Institute of Health Center for Genome Science
Division of Epidemiology and Health Index, Republic of Korea.
Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia, insulin
resistance and relative insulin deficiency. T2D is a leading cause of blindness, renal failure and limb
amputation, and a major risk factor for cardiovascular morbidity and mortality. Over the past years,
the capacity to perform large-scale high density genome-wide association studies (GWASs) has
provided the global view of the genetic etiology of T2D. More than 30 GWASs has been reported for
the T2D in various ethnic groups. Mobile genetic elements such as transposable elements (TEs) are a
major resource of genome instability and several reports suggest that the disease causing TEs in
human genes. However, few studies have been conducted for the TE effects on chronic metabolic
diseases. In this presentation, I will review the T2D GWAS results and will introduce a preliminary
study for the relationship between mobile genetic elements and T2D.
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제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회
Applications of NGS to Understand Genome Biology
Ik-Young Choi
National Instrumentation Center for Environmental Management, College of Agriculture and Life Sciences,
Seoul National University, Seoul 151-921, South Korea
The NGS technologies of genome DNA structure, expression profiling and epigenome
elements have been used widely as approaches in the expertise of genome biology and genetics. The
application to genome study has been particularly developed with the introduction of the nextgeneration DNA sequencer (NGS) Roche/454, Illumina/Solexa and PacBio systems along with
bioinformation analysis technologies of whole-genome de novo assembly, expression profiling, DNA
variation discovery, and genotyping. One of the advantages of the NGS systems is the costeffectiveness to obtain the result of high-throughput DNA sequencing for genome, RNAnome, and
miRNAnome studies. Both massive whole-genome shotgun paired-end sequencing and mate pairedend sequencing data are important steps for constructing de novo assembly of novel genome
sequencing data and for resequencing the samples with a reference genome DNA sequence. To
construct high-quality contig consensus sequences, each DNA fragment read length is important to
obtain de novo assembly with long reading sequences of the Roche/454 and PacBio systems. It is
necessary to have DNA sequence information from a multiplatform NGS with at least 2x and 30x
depth sequence of genome coverage using Roche/454 and Illumina/Solexa, respectively, for effective
an way of de novo assembly, as hybrid assembly for novel genome sequencing would be costeffective. In some cases, Illumina/Solexa data are used to construct scaffolds through de novo
assembly with high coverage depth and large diverse fragment mate paired-end information, even
though they are already participating in assembly and have made many contigs. Massive short-length
reading data from the Illumina/Solexa system is enough to discover DNA variation, resulting in
reducing the cost of DNA sequencing. MAQ and CLC software are useful to both SNP discovery and
genotyping through a comparison of resequencing data to a reference genome. Whole-genome
expression profile data are useful to approach genome system biology with quantification of
expressed RNAs from a whole-genome transcriptome, depending on the tissue samples, such as
control and exposed tissue. The long read sequence data of PacBio are more powerful to find full
length cDNA sequence through de novo assembly in any whole-genome sequenced species. An
average 30x coverage of a transcriptome with short read sequences of Illumina/Solexa is enough to
check expression quantification, compared to the reference EST sequence. In an in silico method,
conserved miRNA and novel miRNA discovery is available on massive miRNAnome data in any
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제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회
species. Particularly, the discovered target genes of miRNA could be robust to approach genome
biology study.
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제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회
Dissecting the genetic structure of Korean population using
genome-wide SNP arrays
Young Jin Kim1,2 and Han Jun Jin3
1
Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex,
Chungcheongbuk-do, Republic of Korea
2
Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-742, Republic of Korea
3
Department of Nanobiomedical Science, Dankook University, Cheonan 330-714, Republic of Korea
Genome-wide SNP arrays have generated unprecedented quantities of data allow the detection
of human evolutionary history and dense genome-wide data also enable the identification of distance
ancestry among individuals or ethnic groups. To explain wider aspects of the genetic structure of
Koreans and the East Asian population, we analyzed 79 individuals from the Korean HapMap project
at 555,352 common single-nucleotide polymorphism loci, and compared this data with the worldwide
population groups with the 53 ethnic groups from Human Genome Diversity Panel (HGDP-CEPH).
Population differentiation (FST), Principal Component Analyses, STRUCTURE and ADMIXTURE
are examined. In general, all the individual samples studies here were classified into subset of ethnic
groups according to their geographical origins. Korean HapMap individuals were grouped together
with East Asian populations from HGDP panel. Recently, a sub-population structure within Korean
population has been reported. Our result, however, revealed the genetic homogeneity of Korean
population. The ADMIXTURE analysis showed that, overall the Korean populations derive 79 % of
their genomic ancestry from southern Asia and have relatively little northern Asian ancestry (21 %).
The present work, therefore, provide the evidence that the male-biased southern-to-northern migration
influenced not only for the genetic make up of the Y chromosome in the Korean population but also,
its autosomal composition.
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제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회
Comprehensive genome- and transcriptome-wide analyses of mutations
associated with microsatellite instability in Korean gastric cancers
Kung Ahn
Theragen Etex Bio Institute, Suwon 443-270, Korea
Microsatellite instability (MSI) is a critical mechanism that drives genetic aberrations in
cancer. To identify the entire MS mutation, we performed the first comprehensive genome- and
transcriptome-wide analyses of mutations associated with MSI in Korean gastric cancer cell lines and
primary tissues. We identified 18,377 MS mutations of five or more repeat nucleotides in coding
sequences and untranslated regions of genes, and discovered 139 individual genes whose expression
was down-regulated in association with UTR MS mutation. In addition, we found that 90.5% of MS
mutations with deletions in gene regions occurred in UTRs. This analysis emphasizes the genetic
diversity of MSI-H gastric tumors and provides clues to the mechanistic basis of instability in
microsatellite unstable gastric cancers.
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제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회
Young Scientist 1.
DNA methylation of transposable element links
alternative splicing in CHM gene
Yi-Deun Jung, Yuri Choi, Ja-Rang Lee, and Heui-Soo Kim*
Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan 609-735, Korea
In eukaryotes genome, activity of transposable elements is suppressed by DNA methylation in
several regions such as promoter, enhancer, and regulatory region. However, in tumor cells, some
alternative transcripts including transposable elements are overexpressed because methylation of
transposable elements loosen. In addition, alternative transcripts play critical roles in differentiation,
development, and disease and are a major source for protein diversity in higher eukaryotes. Transcript
variants (A and B) of the CHM gene were detected in human cancer and normal tissues. Isoform B
transcript is created by an LTR12C element offering a canonical splicing site within the CHM gene.
Furthermore, isoform B transcript showed stronger expression in colon, testis and lung tumor
compared to normal tissues. Thus, we performed bisulfite sequences analysis to study methylation
levels in 2 sites of CHM splicing sites in tumor and adjacent normal tissues samples. The splicing site
of isoform A showed ubiquitous methylation pattern between normal and tumor. However, in isoform
B, we could find two differences between tumor and normal tissues. One is that splicing site derived
from LTR12C element was fully unmethylated in tumor and the other is opposite methylation status
of two CpG sites within alternative exon. In addition, isoform B transcript has several CTCF binding
motif in splicing site and showed increased expression level in CTCF knock-down colon cancer cells.
Thus, we provide evidence that the DNA methylation status and cis-acting factor in transposable
elements could affect alternative splicing.
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제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회
Young Scientist 2.
Evolutionary Fate of Species-Specific Endogenous Retroviruses (ERVs) in
the Human and Chimpanzee Lineages
Seyoung Mun, Wonseok Shin, and Kyudong Han*
Department of Nanobiomedical Science & WCU Research Center, Dankook University, Chunan 330-714, Republic of Korea
Endogenous retroviruses (ERVs) are eukaryotic transposable elements and exist as proviruses
in the vertebrate genomes. It is known that human endogenous retroviruses (HERVs) are classified
into various subfamilies, consisting of nearly ~4.3% of the human genome. Many studies about the
HERV-K elements have been conducted in the human genome but not in other primates. Here, we
tried to identify species-specific endogenous retroviruses: each HERV-K and PtERV which stands for
Pan troglodyte endogenous retrovirus. Through comparative genomics, we identified a total of 28
human-specific HERV-K insertions in human genomic database and 253 chimpanzee-specific PtERV
elements from the chimpanzee reference genome sequence; 121, 110, and 22 copies out of the PtERV
elements belong to full-length, solo LTRs, and truncated elements, respectively. We further
characterized them focusing on their structure and flanking sequences. In addition, we examined their
phylogenetic relationships using various computational methods. Our results showed that the speciesspecific ERV element is one of the sources modifying the genome and thus causing genomic
variations.
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제3회 한국분자세포생물학회 이동성 유전인자분과 학술대회
Young Scientist 3.
Identification of Human-specific AluS elements through comparing
with other non-human primates
Jae Lee and kyudong Han*
Department of Nanobiomedical Science & WCU Research Center, Dankook University, Chunan 330-714, Republic of Korea
The human genome retains a plenty of mobile elements about 45% among which, Alu element,
a family of SINE account for 10% with a > 1 millon copies. These Alu element was reported as
critical factor to cause human genetic disease. To detect human-specific feature distinguished from
other primates, we are focused on AluS element, largest family among various Alu families. First, we
collected total 263 human-specific AluS elements in human genome from previous study, Mills at el.,
2006. And then, we conducted computational analysis to compare human and other primate genome.
As a result, we identified 26 human-specific AluS elements and validated PCR amplification using
human and primate DNA samples. In addition, we also performed polymorphic test to estimate the
number of youngest AluS using 80 population samples. The majority (20/26) were identified as
human-specific elements but other three elements are failed to validate by PCR analysis. The two
elements were not failed to grasp. Because, they are located in Y chromosome whose sequences are
only provided in human and chimpanzee. The rest one element is confirmed incomplete lineage
sorting. Finally, we identified 20 authentic human-specific AluS elements. In addition, we found the
patterns of evolution such as independent insertion in primates, incomplete lineage sorting,
polymorphism among race and individuals, and African-American specific AluS element. Through
this study, we could suggest human-specific AluS elements contributed genomic structural changes
after divergence human and chimpanzee lineage.