Kim, Hea-Ji;Yun, Sin Weon;Yu, Jeong Jin;Yoon, Kyung Lim;Lee, Kyung-Yil;Kil, Hong-Ryang;Kim, Gi Beom;Han, Myung-Ki;Song, Min Seob;Lee, Hyoung Doo;Ha, Kee Soo;Sohn, Sejung;Ebata, Ryota;Hamada, Hiromichi;Suzuki, Hiroyuki;Kamatani, Yoichiro;Kubo, Michiaki;Ito, Kaoru;Onouchi, Yoshihiro;Hong, Young Mi;Jang, Gi Young;Lee, Jong-Keuk;The Korean Kawasaki Disease Genetics Consortium
Genomics & Informatics
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v.16
no.2
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pp.36-41
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2018
Kawasaki disease (KD) is an acute febrile vasculitis predominately affecting infants and children. The dominant incidence age of KD is from 6 months to 5 years of age, and the incidence is unusual in those younger than 6 months and older than 5 years of age. We tried to identify genetic variants specifically associated with KD in patients younger than 6 months or older than 5 years of age. We performed an age-stratified genome-wide association study using the Illumina HumanOmni1-Quad BeadChip data (296 cases vs. 1,000 controls) and a replication study (1,360 cases vs. 3,553 controls) in the Korean population. Among 26 candidate single nucleotide polymorphisms (SNPs) tested in replication study, only a rare nonsynonymous SNP (rs4365796: c.1106C>T, p.Thr369Met) in the lymphoid enhancer binding factor 1 (LEF1) gene was very significantly associated with KD in patients younger than 6 months of age (odds ratio [OR], 3.07; $p_{combined}=1.10{\times}10^{-5}$), whereas no association of the same SNP was observed in any other age group of KD patients. The same SNP (rs4365796) in the LEF1 gene showed the same direction of risk effect in Japanese KD patients younger than 6 months of age, although the effect was not statistically significant (OR, 1.42; p = 0.397). This result indicates that the LEF1 gene may play an important role as a susceptibility gene specifically affecting KD patients younger than 6 months of age.
Athletic performance is an important criteria used for the selection of superior horses. However, little is known about exercise-related epigenetic processes in the horse. DNA methylation is a key mechanism for regulating gene expression in response to environmental changes. We carried out comparative genomic analysis of genome-wide DNA methylation profiles in the blood samples of two different thoroughbred horses before and after exercise by methylated-DNA immunoprecipitation sequencing (MeDIP-Seq). Differentially methylated regions (DMRs) in the pre-and post-exercise blood samples of superior and inferior horses were identified. Exercise altered the methylation patterns. After 30 min of exercise, 596 genes were hypomethy-lated and 715 genes were hypermethylated in the superior horse, whereas in the inferior horse, 868 genes were hypomethylated and 794 genes were hypermethylated. These genes were analyzed based on gene ontology (GO) annotations and the exercise-related pathway patterns in the two horses were compared. After exercise, gene regions related to cell division and adhesion were hypermethylated in the superior horse, whereas regions related to cell signaling and transport were hypermethylated in the inferior horse. Analysis of the distribution of methylated CpG islands confirmed the hypomethylation in the gene-body methylation regions after exercise. The methylation patterns of transposable elements also changed after exercise. Long interspersed nuclear elements (LINEs) showed abundance of DMRs. Collectively, our results serve as a basis to study exercise-based reprogramming of epigenetic traits.
Sodhi, Simrinder Singh;Jeong, Dong Kee;Sharma, Neelesh;Lee, Jun Heon;Kim, Jeong Hyun;Kim, Sung Hoon;Kim, Sung Woo;Oh, Sung Jong
Korean Journal of Poultry Science
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v.40
no.3
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pp.223-234
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2013
Poultry industry is abounding day by day as it engrosses less cost of investment per bird as compared to large animals. Poultry have the most copious genomic tool box amongst domestic animals for the detection of quantitative trait loci (QTL) and marker assisted selection (MAS). Use of multiple markers and least square techniques for mapping of QTL affecting quality and production traits in poultry is in vogue. Examples of genetic tests that are available to or used in industry programs are documented and classified into causative mutations (direct markers), linked markers in population-wide linkage disequilibrium (LD) with the QTL (LD markers), and linked markers in population wide equilibrium with the QTL (LE markers). Development of genome-wide SNP assays, role of 42 K, 60 K (Illumina) and 600 K (Affymetrix$^{(R)}$ Axim$^{(R)}$) SNP chip with next generation sequencing for identification of single nucleotide polymorphism (SNP) has been documented. Hybridization based, PCR based, DNA chip and sequencing based are the major segments of DNA markers which help in conducting of MAS in poultry. Economic index-marker assisted selection (EI-MAS) provides platform for simultaneous selection for production traits while giving due weightage to their marginal economic values by calculating predicted breeding value, using information on DNA markers which are normally associated with relevant QTL. Understanding of linkage equilibrium, linkage dis-equilibrium, relation between the markers and gene of interest are quite important for success of MAS. This kind of selection is the most useful tool in enhancing disease resistance by identifying candidate genes to improve the immune response. The application of marker assisted selection in selection procedures would help in improvement of economic traits in poultry.
Background: Sperm DNA damage is underlying aetiology of poor implantation and pregnancy rates but also affects health of offspring and may also result in denovo mutations in germ line and post fertilization. This may result in complex diseases, polygenic disorders and childhood cancers. Childhood cancer like retinoblastoma (RB) is more prevalent in developing countries and the incidence of RB has increased more than three fold in India in the last decade. Recent studies have documented increased incidence of cancers in children born to fathers who consume alcohol in excess and tobacco or who were conceived by assisted conception. The aetiology of childhood cancer and increased disease burden in these children is lin ked to oxidative stress (OS) and oxidative DNA damage( ODD) in sperm of their fathers. Though several antioxidants are in use to combat oxidative stress, the effect of majority of these formulations on DNA is not known. Yoga and meditation cause significant decline in OS and ODD and aid in regulating OS levels such that reactive oxygen speues meditated signal transduction, gene expression and several other physiological functions are not disrupted. Thus, this study aimed to analyze sperm ODD as a possible etiological factor in childhood cancer and role of simple life style interventions like yoga and meditation in significantly decreasing seminal oxidative stress and oxidative DNA damage and thereby decreasing incidence of childhood cancers. Materials and Methods: A total of 131 fathers of children with RB (non-familial sporadic heritable) and 50 controls (fathers of healthy children) were recruited at a tertiary center in India. Sperm parameters as per WHO 2010 guidelines and reactive oxygen species (ROS), DNA fragmentation index (DFI), 8-hydroxy-2'-deoxy guanosine (8-OHdG) and telomere length were estimated at day 0, and after 3 and 6 months of intervention. We also examined the compliance with yoga and meditation practice and smoking status at each follow-up. Results: The seminal mean ROS levels (p<0.05), sperm DFI (p<0.001), 8-OHdG (p<0.01) levels were significantly higher in fathers of children with RB, as compared to controls and the relative mean telomere length in the sperm was shorter. Levels of ROS were significantly reduced in tobacco users (p<0.05) as well as in alcoholics (p<0.05) after intervention. DFI reduced significantly (p<0.05) after 6 months of yoga and meditation practice in all groups. The levels of oxidative DNA damage marker 8-OHdG were reduced significantly after 3 months (p<0.05) and 6 months (p<0.05) of practice. Conclusions: Our results suggest that OS and ODD DNA may contribute to the development of childhood cancer. This may be due to accumulation of oxidized mutagenic base 8OHdG, and elevated MDA levels which results in MDA dimers which are also mutagenic, aberrant methylation pattern, altered gene expression which affect cell proliferation and survival through activation of transcription factors. Increased mt DNA mutations and aberrant repair of mt and nuclear DNA due to highly truncatred DNA repair mechanisms all contribute to sperm genome hypermutability and persistant oxidative DNA damage. Oxidative stress is also associated with genome wide hypomethylation, telomere shortening and mitochondrial dysfunction leading to genome hypermutability and instability. To the best of our knowledge, this is the first study to report decline in OS and ODD and improvement in sperm DNA integrity following adoption of meditation and yoga based life style modification.This may reduce disease burden in next generation and reduce incidence of childhood cancers.
Based on the place of its origin, pear tree (Pyrus spp.) is largely divided into European pears (P. communis, cultivated mainly in Europe and the U.S.) and Asian pears (P. pyrifolia, P. bretschneideri, and P. ussuriensis, distributed and grown in East Asian countries including China, Japan, and Korea). Most pear trees have 17 chromosomes (diploidy, 2n=2x=34). Their genetic studies and precise cultivar breeding are highly restricted by conditions such as self-incompatibility controlled by S-locus and juvenility as one major character of fruit crops. Genetic studies on Pyrus have been promoted by the development of various molecular markers. These markers are being utilized actively in various genetic studies, including genetic relationship analysis, genetic mapping, and QTL analysis. In addition, research on pear genetic linkage maps has been extended to studies for the identification of QTL for target traits such as disease resistance and genetic loci of useful traits. NGS technology has radically reduced sequencing expenses based on massive parallel reactions to enable high-capacity and high-efficiency. NGS based genome analyses have been completed for Chinese pear 'Danshansuli' and European pear 'Bartlett'. In Korea, GWAS for agricultural valuable traits such as floral structure, ripening, and total soluble contents have been conducted through resequencing. GBS has been performed for 'Whangkeumbae', 'Cheongsilri', and 'Minibae'.
Objective: Porcine respiratory disease is one of the most important health problems causing significant economic losses. To understand the genetic basis for susceptibility to swine enzootic pneumonia (EP) in pigs, we detected 102,809 single nucleotide polymorphisms in a total of 249 individuals based on genome-wide sequencing data. Methods: Genome comparison of susceptibility to swine EP in three pig breeds (Jinhua, Erhualian, and Meishan) with two western lines that are considered more resistant (Duroc and Landrace) using cross-population extended haplotype homozygosity and F-statistic (FST) statistical approaches identified 691 positively selected genes. Based on quantitative trait loci, gene ontology terms and literature search, we selected 14 candidate genes that have convincible biological functions associated with swine EP or human asthma. Results: Most of these genes were tested by several methods including transcription analysis and candidate genes association study. Among these genes: cytochrome P450 1A1 and catenin beta 1 (CTNNB1) are involved in fertility; transforming growth factor beta receptor 3 plays a role in meat quality traits; Wnt family member 2, CTNNB1 and transcription factor 7 take part in adipogenesis and fat deposition simultaneously; plasminogen activator, urokinase receptor (completely linked to AXL receptor tyrosine kinase, r2 = 1) plays an essential role in the successful ovulation of matured oocytes in pigs; colipase like 2 (strongly linked to SAM pointed domain containing ETS transcription factor, r2 = 0.848) is involved in male fertility. Conclusion: These adverse genes susceptible to swine EP may be selected while selecting for economic traits (especially reproduction traits) due to pleiotropic and hitchhiking effect of linked genes. Our study provided a completely new point of view to understand the genetic basis for susceptibility or resistance to swine EP in pigs thereby, provides insight for designing sustainable breed selection programs. Finally, the candidate genes are crucial due to their potential roles in respiratory diseases in a large number of species, including human.
To understand the molecular structure and pathogenesis mechanism of Korean garlic viruses, we have isolated cDNA clones for garlic viruses. The partial nucleotide sequences of 24 cDNA clones were determined and those of five clones containing poly(A) tail were compared with sequences of other plant viruses. One of these clones, V9, has a primary structure similar to the carlavirus group, suggesting that the clone V9 derived from a part of garlic latent virus (GLV). Northern blot analysis with the clone V9 as a probe demonstrated that GLV genome is 8.5 knt long and has a poly(A) tail. The clone V9 encodes coat protein (CP) of 33 kDa and nucleic acid binding protein of 10 kDa in different reading frame. The hexanucleotide motif, 5'-ACCUAA, which is conserved in the 3' noncoding region arid was proposed to be a cis-acting element involved in the production of negative strand genomic RNA was noticed. Complementary sequence to the hexanucleotide motif, 5'-TTAGGT, is also found in the positive strand of V9 RNA. The putative CP gene was cloned into the pRSET-A expression vector and expressed in E. coli BL21. The expressed recombinant V9CP protein was purified by $Ni^{2+}$ NTA affinity chromatography. The anti-V9CP antibody recognizes 34 kDa polypeptide which could be CP of GLV in infected garlic leaf extract. Immunoblot and Northern blot analysis of various cultivars shows wide occurrence of GLV in Korean garlic plants.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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v.37
no.6
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pp.550-555
/
2011
Chromosomal loss of heterozygosity (LOH) is a common mechanism for the inactivation of tumor suppressor genes in human epithelial cancers. LOH patterns can be generated through allelotyping using polymorphic microsatellite markers; however, owing to the limited number of available microsatellite markers and the requirement for large amounts of DNA, only a modest number of microsatellite markers can be screened. Hybridization to single nucleotide polymorphism (SNP) arrays using Affymetarix GeneChip Mapping 10 K 2.0 Array is an efficient method to detect genome-wide cancer LOH. We determined the presence of LOH in oral SCCs using these arrays. DNA was extracted from tissue samples obtained from 10 patients with tongue SCCs who presented at the Hospital of Tokyo Dental College. We examined the presence of LOH in 3 of the 10 patients using these arrays. At the locus that had LOH, we examined the presence of LOH using microsatellite markers. LOH analysis using Affymetarix GeneChip Mapping 10K Array showed LOH in all patients at the 1q31.1. The LOH regions were detected and demarcated by the copy number 1 with the series of three SNP probes. LOH analysis of 1q31.1 using microsatellite markers (D1S1189, D1S2151, D1S2595) showed LOH in all 10 patients (100). Our data may suggest that a putative tumor suppressor gene is located at the 1q31.1 region. Inactivation of such a gene may play a role in tongue tumorigenesis.
Single nucleotide polymorphisms (SNPs) are the most abundant forms of human genetic variations and resources for mapping complex genetic traits and disease association studies. We have constructed a linkage disequilibrium (LD) map of chromosome 22 in Korean samples and compared it with those of other populations, including Yorubans in Ibadan, Nigeria (YRI), Centre d'Etude du Polymorphisme Humain (CEPH) reference families (CEU), Japanese in Tokyo (JPT) and Han Chinese in Beijing (CHB) in the HapMap database. We genotyped 4681 of 111,448 publicly available SNPs in 90 unrelated Koreans. Among genotyped SNPs, 4167 were polymorphic. Three hundred and five LD blocks were constructed to make up 18.6% (6.4 of 34.5 Mb) of chromosome 22 with 757 tagSNPs and 815 haplotypes (frequency $\geq$ 5.0%). Of 3430 common SNPs genotyped in all five populations, 514 were monomorphic in Koreans. The CHB + JPT samples have more than a 72% overlap with the monomorphic SNPs in Koreans, while the CEU + YRI samples have less than a 38% overlap. The patterns of hot spots and LD blocks were dispersed throughout chromosome 22, with some common blocks among populations, highly concordant between the three Asian samples. Analysis of the distribution of chimpanzee-derived allele frequency (DAF), a measure of genetic differentiation, Fst levels, and allele frequency difference (AFD) among Koreans and the HapMap samples showed a strong correlation between the Asians, while the CEU and YRI samples showed a very weak correlation with Korean samples. Relative distance as a quantitative measurement based upon DAF, Fst, and AFD indicated that all three Asian samples are very proximate, while CEU and YRI are significantly remote from the Asian samples. Comparative genome-wide LD studies provide useful information on the association studies of complex diseases.
Journal of the Korean Data and Information Science Society
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v.26
no.6
/
pp.1249-1258
/
2015
DGAT1(diacylglycerol O-acyltransferase1) gene is well known as a major gene of milk production in dairy cattle. This study was conducted to investigate how the DGAT1 gene effect on milk yield was appeared from the genome wide association (GWA) using high density whole genome SNP chip. The data set used in this study consisted of 353 Korean Holstein sires with 50k SNP genotypes and deregressed estimated breeding values of milk yield. After quality control 41,051 SNPs were selected and locations on chromosome were mapped using UMD 3.1. Bayesian regression of BayesB method (pi=0.99) was used to estimate the SNP effects and genomic breeding values. Percentages of variance explained by 1 Mb non-overlapping windows were calculated to detect the QTL region. As the result of this study, top 1 and 3 of 2,516 windows were seen around DGAT1 gene region and 0.51% and 0.48% of genetic variance were explained by these two windows. Although SNPs on the DGAT1 gene region are excluded in commercial 50k SNP chip, the effect of DGAT1 gene seem to be reflected on GWA by the SNPs which are in linkage disequilibrium with DGAT1 gene.
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