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Mun S.,Dankook University | Mun S.,DKU Theragen Institute for NGS Analysis DTiNa | Lee J.,Dankook University | Lee J.,University of Florida | And 5 more authors.
PLoS ONE | Year: 2014

Endogenous retroviruses (ERVs), eukaryotic transposable elements, exist as proviruses in vertebrates including primates and contribute to genomic changes during the evolution of their host genomes. Many studies about ERVs have focused on the elements residing in the human genome but only a few studies have focused on the elements which exist in non-human primate genomes. In this study, we identified 256 chimpanzee-specific endogenous retrovirus copies (PtERVs: Pan troglodyte endogenous retroviruses) from the chimpanzee reference genome sequence through comparative genomics. Among the chimpanzee-specific ERV copies, 121 were full-length chimpanzee-specific ERV elements while 110 were chimpanzee-specific solitary LTR copies. In addition, we found eight potential retrotransposition-competent full-length chimpanzee-specific ERV copies containing an intact env gene, and two of them were polymorphic in chimpanzee individuals. Through computational analysis and manual inspection, we found that some of the chimpanzee-specific ERVs have propagated via non-classical PtERV insertion (NCPI), and at least one of the PtERVs may have played a role in creating an alternative transcript of a chimpanzee gene. Based on our findings in this study, we state that the chimpanzee-specific ERV element is one of the sources of chimpanzee genomic variations, some of which might be related to the alternative transcripts in the chimpanzee population. © 2014 Mun et al.


Jun J.,Personal Genomics Institute | Cho Y.S.,Personal Genomics Institute | Cho Y.S.,The Genomics Institute | Hu H.,Personal Genomics Institute | And 13 more authors.
BMC Genomics | Year: 2014

Background: The horse (Equus ferus caballus) is one of the earliest domesticated species and has played an important role in the development of human societies over the past 5,000 years. In this study, we characterized the genome of the Marwari horse, a rare breed with unique phenotypic characteristics, including inwardly turned ear tips. It is thought to have originated from the crossbreeding of local Indian ponies with Arabian horses beginning in the 12th century. Results: We generated 101 Gb (~30 × coverage) of whole genome sequences from a Marwari horse using the Illumina HiSeq2000 sequencer. The sequences were mapped to the horse reference genome at a mapping rate of ~98% and with ~95% of the genome having at least 10 × coverage. A total of 5.9 million single nucleotide variations, 0.6 million small insertions or deletions, and 2,569 copy number variation blocks were identified. We confirmed a strong Arabian and Mongolian component in the Marwari genome. Novel variants from the Marwari sequences were annotated, and were found to be enriched in olfactory functions. Additionally, we suggest a potential functional genetic variant in the TSHZ1 gene (p.Ala344>Val) associated with the inward-turning ear tip shape of the Marwari horses. Conclusions: Here, we present an analysis of the Marwari horse genome. This is the first genomic data for an Asian breed, and is an invaluable resource for future studies of genetic variation associated with phenotypes and diseases in horses. © 2014 Jun et al.


Lee W.,Dankook University | Mun S.,Dankook University | Mun S.,U.S. National Institutes of Health | Kang K.,Dankook University | And 3 more authors.
Gene | Year: 2015

Alu elements are the most successful short interspersed elements in primate genomes and their retrotransposition is a major source of genomic expansion. Alu elements integrate into genomic regions through target-site primed reverse transcription, which generates target site duplications (TSDs). Unexpectedly, we have identified target site triplications (TSTs) at some loci, where two Alu elements in tandem share one direct repeat. Thus, the three copies of the repeat are present. We located 212 TST loci in the human genome and examined 25 putative human-specific TST loci using PCR validation. As a result, 12 human-specific TST loci were identified. These findings suggest that unequal homologous recombination between TSDs can lead to TST. Through this mechanism, the copy number of Alu elements could have increased in primate genomes without new Alu retrotransposition events. This study provides new insight into the augmentation of Alu elements in the primate genome. © 2015 Elsevier B.V.


Kim Y.-J.,Dankook University | Kim Y.-J.,DKU Theragen Institute for NGS Analysis DTiNa | Ahn K.,Theragen BiO Institute | Gim J.-A.,Pusan National University | And 4 more authors.
Gene | Year: 2015

Segmental duplication, or low-copy repeat (LCR) event, occurs during primate evolution and is an important source of genomic diversity, including gain or loss of gene function. The human chromosome 7q 11.23 is related to the William-Beuren syndrome and contains large region-specific LCRs composed of blocks A, B, and C that have different copy numbers in humans and different primates. We analyzed the structure of POM121, NSUN5, FKBP6, and TRIM50 genes in the LCRs of block C. Based on computational analysis, POM121B created by a segmental duplication acquired a new exonic region, whereas NSUN5B (NSUN5C) showed structural variation by integration of HERV-K LTR after duplication from the original NSUN5 gene. The TRIM50 gene originally consists of seven exons, whereas the duplicated TRIM73 and TRIM74 genes present five exons because of homologous recombination-mediated deletion. In addition, independent duplication events of the FKBP6 gene generated two pseudogenes at different genomic locations. In summary, these clustered genes are created by segmental duplication, indicating that they show dynamic evolutionary events, leading to structure variation in the primate genome. © 2015 Elsevier B.V.


Kim Y.-J.,Dankook University | Kim Y.-J.,DKU Theragen Institute for NGS Analysis DTiNa
Genes and Genomics | Year: 2014

Transposable elements (TEs) are interspersed in the host genomic regions, and induce various effects to the host. Recent study shows TE sequences can provide microRNA (miRNA) sequences which have a crucial role in the organisms by silencing target mRNAs. In this study, 14 TE-derived miRNAs were identified by overlapping >50 % with expressed sequence tag. Among them, miR-330, miR-648, miR-1254, and miR-1825 were examined regarding their expression patterns and evolutionary conservation in various species. MiR-330 and miR-648 were highly expressed in the bone marrow and cerebellum tissues, while miR-1825 showed high expression in the fetal liver tissue. Additionally, MiR-1254 showed dominant expression in the skeletal muscle. These TE-derived miRNAs showed an inhibitory effect on the expression of their target genes, MLL2 and ARHGEF12. These findings confirmed that TEs play important roles to regulate gene expression by providing miRNA sequences and they may contribute to the evolution of biological complexity in human genome. © 2014, The Genetics Society of Korea and Springer-Science and Media.


Kim T.,Dankook University | Lee W.,Dankook University | Lee W.,DKU Theragen Institute for NGS Analysis DTiNa | Han K.,Dankook University | And 2 more authors.
Genes and Genomics | Year: 2015

Although there are many applications available for the analysis of chromatin immunoprecipitation with massively parallel DNA sequencing (ChIP-seq), users need some knowledge about the installation, alignment, and peak calling procedures prior to the analysis. Here, we present an easy-to-use application for ChIP-seq analysis called AutoChIP. With AutoChIP, installation of necessary programs, alignment of unmapped reads to a reference genome, and identification of genome-wide binding sites can be done in a single step with a large set of ChIP-seq data. Evaluation of the cocktail algorithm implemented in AutoChIP showed that it outperformed a single ChIP-seq tool in terms of the ratio of motif occurrences and the average height of normalized read density over the identified peaks. In addition, annotation of the identified peaks with the known gene and repeat elements information provides a comprehensive picture of the genome-wide binding sites of given proteins. Overall, AutoChIP provides a comprehensive platform to analyze a large set of ChIP-seq data in one step. © 2014, The Genetics Society of Korea and Springer-Science and Media.


Lee J.,Dankook University | Kim Y.-J.,Dankook University | Kim Y.-J.,DKU Theragen Institute for NGS Analysis DTiNa | Mun S.,Dankook University | And 4 more authors.
Gene | Year: 2015

Mobile elements are responsible for ~. 45% of the human genome. Among them is the Alu element, accounting for 10% of the human genome (> 1.1. million copies). Several studies of Alu elements have reported that they are frequently involved in human genetic diseases and genomic rearrangements. In this study, we investigated the AluS subfamily, which is a relatively old Alu subfamily and has the highest copy number in primate genomes. Previously, a set of 263 human-specific AluS insertions was identified in the human genome. To validate these, we compared each of the human-specific AluS loci with its pre-insertion site in other primate genomes, including chimpanzee, gorilla, and orangutan. We obtained 24 putative human-specific AluS candidates via the in silico analysis and manual inspection, and then tried to verify them using PCR amplification and DNA sequencing. Through the PCR product sequencing, we were able to detect two instances of near-parallel Alu insertions in nearby sites that led to computational false negatives. Finally, we computationally and experimentally verified 23 human-specific AluS elements. We reported three alternative Alu insertion events, which are accompanied by filler DNA and/or Alu retrotransposition mediated-deletion. Bisulfite sequencing was carried out to examine DNA methylation levels of human-specific AluS elements. The results showed that fixed AluS elements are hypermethylated compared with polymorphic elements, indicating a possible relation between DNA methylation and Alu fixation in the human genome. © 2014 Elsevier B.V.


Lee S.,Dankook University | Oh S.,Dankook University | Kang K.,Dankook University | Han K.,Dankook University | Han K.,DKU Theragen Institute for NGS Analysis DTiNa
BioMed Research International | Year: 2014

The availability of several whole genome sequences makes comparative analyses possible. In primate genomes, the priority of transposable elements (TEs) is significantly increased because they account for 45% of the primate genomes, they can regulate the gene expression level, and they are associated with genomic fluidity in their host genomes. Here, we developed the BLAST-like alignment tool (BLAT) based comparative analysis for transposable elements (BLATCAT) program. The BLATCAT program can compare specific regions of six representative primate genome sequences (human, chimpanzee, gorilla, orangutan, gibbon, and rhesus macaque) on the basis of BLAT and simultaneously carry out RepeatMasker and/or Censor functions, which are widely used Windows-based web-server functions to detect TEs. All results can be stored as a HTML file for manual inspection of a specific locus. BLATCAT will be very convenient and efficient for comparative analyses of TEs in various primate genomes. © 2014 Sangbum Lee et al.


Kang D.,Dankook University | Kim Y.-J.,Dankook University | Kim Y.-J.,DKU Theragen Institute for NGS Analysis DTiNa | Hong K.,Dankook University | And 2 more authors.
Genes and Genomics | Year: 2015

High-throughput sequencing analyses have revealed that transposable elements (TEs) comprise approximately half of the human genome and frequently involved in genomic rearrangements and instability by various mechanisms. Interestingly, many noncoding RNAs (ncRNAs) contain TEs and the TE-containing ncRNAs that have been implicated in cellular processes and various diseases in mammals. In this study, we retrieved 94 human long noncoding RNAs (lncRNAs; >200 nucleotides in length) from lncRNAdb and analyzed TEs which are embedded within the lncRNAs, focusing on their chromosomal distribution. The result showed that TEs occupy ~27 % of the lncRNA transcripts in mass and lncRNA containing TEs are enriched in human chromosome 11. We further analyzed subfamily of the TEs and found that most of the TEs belong to AluSx and L1 which are the most successful TE subfamilies in the human genome. Numerous lncRNAs have been reported to be expressed in a cell-type specific manner. Thus, using reverse transcription PCR with specific primers for the lncRNAs, we examined their expression pattern in human normal tissues and cancer cells. Most of the lncRNAs were universally amplified from 20 different types of normal human tissues but some of them displayed tissue-specific expression. Especially, 11 lncRNAs were expressed only in human cancer cells, implying the possibility of their involvement in carcinogenesis. © 2014, The Genetics Society of Korea and Springer-Science and Media.


Ha J.,Dankook University | Ha J.,DKU Theragen Institute for NGS Analysis DTiNa | Lee W.,Dankook University | Mun S.,Dankook University | And 3 more authors.
Genes and Genomics | Year: 2016

The human genome has various genomic structural variations such as insertion/deletions between human individuals. These structural variations have led to genomic fluidity and rearrangements in individuals and populations. To investigate Korean-specific structural genomic variations, we performed next generation sequencing with 30× mean coverage from 27 Korean individuals using illumina-HiSeq 2000 platform. We collected a total of 119 deletion loci as transposable element-mediated Korean-specific deletion (KSD) candidates. Of the 119 loci, 35 were filtered out due to computational overlapping regions. A total of 78 loci were validated by PCR amplification with 27 Korean individuals and 80 human individuals from four different populations. We confirmed deletion breakpoints of the 78 loci using Sanger sequencing. We also investigated different deletion mechanisms based on sequencing alignment analysis. We found at least one KSD locus in 80 human individual panel. It has not been previously reported in human genomes. Here, for the first time, we report transposable element-mediated KSD study based on whole genome sequencing data of 27 Korean. © 2015, The Genetics Society of Korea and Springer-Science and Media.

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