• Title/Summary/Keyword: GWAS

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A New Paradigm to Mitigate Osteosarcoma by Regulation of MicroRNAs and Suppression of the NF-${\kappa}B$ Signaling Cascade

  • Mongre, Raj Kumar;Sodhi, Simrinder Singh;Ghosh, Mrinmoy;Kim, Jeong Hyun;Kim, Nameun;Sharma, Neelesh;Jeong, Dong Kee
    • Development and Reproduction
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    • v.18 no.4
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    • pp.197-212
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    • 2014
  • Osteosarcoma (OS) is one of the most common malignant primary bone tumors and NF-${\kappa}B$ appears to play a causative role, but the mechanisms are poorly understood. OS is one of the pleomorphic, highly metastasized and invasive neoplasm which is capable to generate osteoid, osteoclast and osteoblast matrix. Its high incidence has been reported in adolescent and children. Cell signal cascade is the pivotal functional mechanism acquired during the differentiation, proliferation, growth and survival of the cells in neoplasm including OS. The major limitation to the success of chemotherapy in OS is the development of multidrug resistance (MDR). Answers to all such queries might come from the knock-in experiments in which the combined approach of miRNAs with NF-${\kappa}B$ pathway is put into use. Abnormal miRNAs can modulate several epigenetical switching as a hallmark of number of diseases via different cell signaling. Studies on miRNAs have opened up the new avenues for both the diagnosis and treatment of cancers including OS. Collectively, through the present study an attempt has been made to establish a new systematic approach for the investigation of microRNAs, bio-physiological factors and their target pairs with NF-${\kappa}B$ to ameliorate oncogenesis with the "bridge between miRNAs and NF-${\kappa}B$". The application of NF-${\kappa}B$ inhibitors in combination with miRNAs is expected to result in a more efficient killing of the cancer stem cells and a slower or less likely recurrence of cancer.

Genome wide association test to identity QTL for dressing percentage in Hanwoo (전장 유전체 관련성 분석을 통한 한우 도체수율 관련 양적형질좌위 탐색)

  • Lee, Seung Hwan;Lim, Dajeong;Dang, Chang Gwan;Chang, Sun Sik;Kim, Hyeong Cheul;Jeon, Gi Jun;Yeon, Seong Hum;Jang, Gul Won;Park, Eung Woo;Oh, Jae Don;Lee, Hak Kyo;Lee, Jun Heon;Kang, Hee Sul;Yoon, Duhak
    • Korean Journal of Agricultural Science
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    • v.40 no.2
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    • pp.155-162
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    • 2013
  • Genome-wide association study was performed on data from 266 Hanwoo steers derived from 66 sire using bovine 10K mapping chip in Hanwoo (Korean Cattle). SNPs were excluded from the analysis if they failed in over 5% of the genotypes, had median GC scores below 0.6, had GC scores under 0.6 in less than 90% of the samples, deviated in heterozygosity more than 3 standard deviations from the other SNPs and were out of Hardy-Weinberg equilibrium for a cutoff p-value of $1^{-15}$. Unmapped and SNPs on sex chromosomes were also excluded. A total of 4,522 SNPs were included in the analysis. To test an association between SNP and QTL, GWAS for five genetic mode (additive, dominant, overdominant, recessive and codominant) was implemented in this study. Three SNPs (rs29018694, ss46526851 and rs29018222) at a threshold p< $1.11{\times}10^{-5}$ were detected on BTA12 and BTA21 for dressing percentages in codominant and recessive genetic mode. The G allele for rs29018694 has 4.9% higher dressing percentage than A allele, while the T allele for ss46526851 has 2.57 % higher dressing percentage than C allele. Therefore, rs29018694 SNP showed a bigger effect than the other two SNPs (ss46526851 and rs29018222) in this study. In conclusion, this study identifies three loci with moderate effects and many loci with infinitesimally small effect across genome in Hanwoo.

Analysis of Chicken Feather Color Phenotypes Classified by K-Means Clustering using Reciprocal F2 Chicken Populations (K-Means Clustering으로 분류한 닭 깃털색 표현형의 분석)

  • Park, Jongho;Heo, Seonyeong;Kim, Minjun;Cho, Eunjin;Cha, Jihye;Jin, Daehyeok;Koh, Yeong Jun;Lee, Seung-Hwan;Lee, Jun Heon
    • Korean Journal of Poultry Science
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    • v.49 no.3
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    • pp.157-165
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    • 2022
  • Chickens are a species of vertebrate with varying colors. Various colors of chickens must be classified to find color-related genes. In the past, color scoring was performed based on human visual observation. Therefore, chicken colors have not been measured with precise standards. In order to solve this problem, a computer vision approach was used in this study. Image quantization based on k-means clustering for all pixels of RGB values can objectively distinguish inherited colors that are expressed in various ways. This study was also conducted to determine whether plumage color differences exist in the reciprocal cross lines between two breeds: black Yeonsan Ogye (YO) and White Leghorn (WL). Line B is a crossbred line between YO males and WL females while Line L is a reciprocal crossbred line between WL males and YO females. One male and ten females were selected for each F1 line, and full-sib mating was conducted to generate 883 F2 birds. The results indicate that the distribution of light and dark colors of k-means clustering converged to 7:3. Additionally, the color of Line B was lighter than that of Line L (P<0.01). This study suggests that the genes underlying plumage colors can be identified using quantification values from the computer vision approach described in this study.

Genome-wide association study for loin muscle area of commercial crossbred pigs

  • Menghao Luan;Donglin Ruan;Yibin Qiu;Yong Ye;Shenping Zhou;Jifei Yang;Ying Sun;Fucai Ma;Zhenfang Wu;Jie Yang;Ming Yang;Enqin Zheng;Gengyuan Cai;Sixiu Huang
    • Animal Bioscience
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    • v.36 no.6
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    • pp.861-868
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    • 2023
  • Objective: Loin muscle area (LMA) is an important target trait of pig breeding. This study aimed to identify single nucleotide polymorphisms (SNPs) and genes associated with LMA in the Duroc×(Landrace×Yorkshire) crossbred pigs (DLY). Methods: A genome-wide association study was performed using the Illumina 50K chip to map the genetic marker and genes associated with LMA in 511 DLY pigs (255 boars and 256 sows). Results: After quality control, we detected 35,426 SNPs, including six SNPs significantly associated with LMA in pigs, with MARC0094338 and ASGA0072817 being the two key SNPs responsible for 1.77% and 2.48% of the phenotypic variance of LMA, respectively. Based on previous research, we determined two candidate genes (growth hormone receptor [GHR] and 3-oxoacid Co A-transferase 1 [OXCT1]) that are associated with fat deposition and muscle growth and found further additional genes (MYOCD, ARHGAP44, ELAC2, MAP2K4, FBXO4, FBLL1, RARS1, SLIT3, and RANK3) that are presumed to have an effect on LMA. Conclusion: This study contributes to the identification of the mutation that underlies quantitative trait loci associated with LMA and to future pig breeding programs based on marker-assisted selection. Further studies are needed to elucidate the role of the identified candidate genes in the physiological processes involved in LMA regulation.

Genome Wide Association Study for Phytophthora sojae Resistance with the Two Races Collected from Main Soybean Production Area in Korea with 210 Soybean Natural Population

  • Beom-Kyu Kang;Su-Vin Heo;Ji-Hee Park;Jeong-Hyun Seo;Man-Soo Choi;Jun-Hoi Kim;Jae-Bok Hwang;Ji-Yeon Ko;Yun-Woo Jang;Young-Nam Yun;Choon-Song Kim
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2022.10a
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    • pp.202-202
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    • 2022
  • Recently days, soybean production in paddy field is increasing, from 4,422 ha in 2016 to 10,658 ha in 2021 in Korea. It is easy for Phytophthora stem and root rot (PSR) occurring in paddy field condition, when it is poorly drained soils with a high clay content, and temporary flooding and ponding. Therefore PSR resistant soybean cultivar is required. The objective of this study is to identify QTL region and candidate genes relating to PSR resistance of the race in main soybean cultivation area in Korea. 210 soybean materials including cultivars and germplasm were used for inoculation and genome-wide association study (GWAS). Inoculation was conducted using stem-scar method with 2 replications in 2-year for the race 3053 from Kimje and 3617 from Andong. 210 materials were genotyped with Soya SNP 180K chip, and structure analysis and association mapping were conducted with QTLMAX V2. The results of inoculation showed that survival ratio ranged from 0% to 96.7% and mean 9.7% for 3053 and ranged from 0% to 100% and mean 7.6% for 3617. Structure analysis showed linkage disequillibrium (LD) was decayed below r2=0.5 at 335kb of SNP distance. Significant SNPs (LOD>7.0) were identified in Chr 1, 2, 3, 4, 5, 11, 14, 15 for 3053 and Chr 1, 2, 3, 7, 10, 14 for 3617. Especially, LD blocks (AX-90455181;15,056,628bp~AX-90475572;15,298,872bp) in Chr 2 for 3053 and 3067 were duplicated. 29 genes were identified on these genetic regions including Glyma.02gl47000 relating to ribosome recycling factor and defense response to fungus in Soybase.

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A genome-wide association study for the fatty acid composition of breast meat in an F2 crossbred chicken population

  • Eunjin Cho;Minjun Kim;Sunghyun Cho;Hee-Jin So;Ki-Teak Lee;Jihye Cha;Daehyeok Jin;Jun Heon Lee
    • Journal of Animal Science and Technology
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    • v.65 no.4
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    • pp.735-747
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    • 2023
  • The composition of fatty acids determines the flavor and quality of meat. Flavor compounds are generated during the cooking process by the decomposition of volatile fatty acids via lipid oxidation. A number of research on candidate genes related to fatty acid content in livestock species have been published. The majority of these studies focused on pigs and cattle; the association between fatty acid composition and meat quality in chickens has rarely been reported. Therefore, this study investigated candidate genes associated with fatty acid composition in chickens. A genome-wide association study (GWAS) was performed on 767 individuals from an F2 crossbred population of Yeonsan Ogye and White Leghorn chickens. The Illumina chicken 60K significant single-nucleotide polymorphism (SNP) genotype data and 30 fatty acids (%) in the breast meat of animals slaughtered at 10 weeks of age were analyzed. SNPs were shown to be significant in 15 traits: C10:0, C14:0, C18:0, C18:1n-7, C18:1n-9, C18:2n-6, C20:0, C20:2, C20:3n-6, C20:4n-6, C20:5n-3, C24:0, C24:1n-9, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA). These SNPs were mostly located on chromosome 10 and around the following genes: ACSS3, BTG1, MCEE, PPARGC1A, ACSL4, ELOVL4, CYB5R4, ME1, and TRPM1. Both oleic acid and arachidonic acid contained the candidate genes: MCEE and TRPM1. These two fatty acids are antagonistic to each other and have been identified as traits that contribute to the production of volatile fatty acids. The results of this study improve our understanding of the genetic mechanisms through which fatty acids in chicken affect the meat flavor.

Association of Six Susceptibility Loci with Prostate Cancer in Northern Chinese Men

  • Zhang, Yu-Rong;Xu, Yong;Yang, Kuo;Liu, Ming;Wei, Dong;Zhang, Yao-Guang;Shi, Xiao-Hong;Wang, Jian-Ye;Yang, Fan;Wang, Xin;Liang, Si-Ying;Zhao, Cheng-Xiao;Wang, Fei;Chen, Xin;Sun, Liang;Zhu, Xiao-Quan;Zhu, Ling;Yang, Yi-Ge;Tang, Lei;Jiao, Hai-Yan;Huo, Zheng-Hao;Yang, Ze
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.12
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    • pp.6273-6276
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    • 2012
  • Background/Aim: Six prostate cancer (PCa) susceptibility loci were identified in a genome-wide association study (GWAS) in populations of European decent. However, the associations of these 6 single-nucleotide polymorphisms (SNPs) with PCa has remained tobe clarified in men in Northern China. This study aimed to explore the loci associated with PCa risk in a Northern Chinese population. Methods: Blood samples and clinical information of 289 PCa patients and 288 controls from Beijing and Tianjin were collected. All risk SNPs were genotyped using polymerase chain reaction (PCR)-high resolution melting curve technology and gene sequencing. Associations between PCa and clinical covariates (age at diagnosis, prostate-specific antigen [PSA], Gleason score, tumor stage, and level of aggressiveness) and frequencies of alleles and genotypes of these SNPs were analyzed using genetic statistics. Results: Among the candidate SNPs, 11p15 (rs7127900, A) was associated with PCa risk (P = 0.02, odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.09-2.46). Genotypes showed differences between cases and controls on 11p15 (rs7127900, A), 11q13 (rs7931342, T), and HNF1B (rs4430796, A) (P = 0.03, P = 0.01, and P = 0.04, respectively). The genotype TG on 11q13 (rs7931342, T) was positively associated with an increased Gleason score (P = 0.04, OR = 2.15, 95% CI = 1.02-4.55). Patients carrying TG on 17q24 (rs1859962, G) were negatively associated with an increased body mass index (BMI) (P = 0.03, OR = 0.44, 95% CI = 0.21-0.92) while those with AG on HNF1B (rs4430796, A) were more likely to have PSA increase (P = 0.002). Conclusion: Our study suggests that 11p15 (rs7127900, A) could be a susceptibility locus associated with PCa in Northern Chinese. Genotype TG on 11q13 (rs7931342, T) could be related to an increased Gleason score, AG on HNF1B (rs4430796, A) could be associated with PSA increase, and TG on 17q24 (rs1859962, G) could be negatively associated with an increased BMI in Chinese men with PCa.

Current status and prospects of molecular marker development for systematic breeding program in citrus (감귤 분자육종을 위한 분자표지 개발 현황 및 전망)

  • Kim, Ho Bang;Kim, Jae Joon;Oh, Chang Jae;Yun, Su-Hyun;Song, Kwan Jeong
    • Journal of Plant Biotechnology
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    • v.43 no.3
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    • pp.261-271
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    • 2016
  • Citrus is an economically important fruit crop widely growing worldwide. However, citrus production largely depends on natural hybrid selection and bud sport mutation. Unique botanical features including long juvenility, polyembryony, and QTL that controls major agronomic traits can hinder the development of superior variety by conventional breeding. Diverse factors including drastic changes of citrus production environment due to global warming and changes in market trends require systematic molecular breeding program for early selection of elite candidates with target traits, sustainable production of high quality fruits, cultivar diversification, and cost-effective breeding. Since the construction of the first genetic linkage map using isozymes, citrus scientists have constructed linkage maps using various DNA-based markers and developed molecular markers related to biotic and abiotic stresses, polyembryony, fruit coloration, seedlessness, male sterility, acidless, morphology, fruit quality, seed number, yield, early fruit setting traits, and QTL mapping on genetic maps. Genes closely related to CTV resistance and flesh color have been cloned. SSR markers for identifying zygotic and nucellar individuals will contribute to cost-effective breeding. The two high quality citrus reference genomes recently released are being efficiently used for genomics-based molecular breeding such as construction of reference linkage/physical maps and comparative genome mapping. In the near future, the development of DNA molecular markers tightly linked to various agronomic traits and the cloning of useful and/or variant genes will be accelerated through comparative genome analysis using citrus core collection and genome-wide approaches such as genotyping-by-sequencing and genome wide association study.

Construction of Genetic Linkage Map and Identification of Quantitative Trait Loci in Populus davidiana using Genotyping-by-sequencing (Genotyping-by-sequencing 기법을 이용한 사시나무(Populus davidiana) 유전연관지도 작성 및 양적형질 유전자좌 탐색)

  • Suvi Kim;Yang-gil Kim;Dayoung Lee;Hye-jin Lee;Kyu-Suk Kang
    • Journal of Korean Society of Forest Science
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    • v.112 no.1
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    • pp.40-56
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    • 2023
  • Tree species within the Populus genus grow rapidly and have an excellent capacity to absorb carbon, conferring substantial ability to effective purify the environment. Poplar breeding can be achieved rapidly and efficiently if a genetic linkage map is constructed and quantitative trait loci (QTLs) are identified. Here, a high-density genetic linkage map was constructed for the control pollinated progeny using the genotyping-by-sequencing (GBS) technique, which is a next-generation sequencing method. A search was also performed for the genes associated with quantitative traits located in the genetic linkage map by examining the variables of height and diameter at root collar, and resilience to insect damage. The height and diameter at root collar were measured directly, while the ability to recover from insect damage was scored in a 4-year-old breeding population of aspen hybrids (Odae19 × Bonghyeon4 F1) established in the research forest of Seoul National University. After DNA extraction, paternity was confirmed using five microsatellite markers, and only the individuals for which paternity was confirmed were used for the analysis. The DNA was cut using restriction enzymes and the obtained DNA fragments were prepared using a GBS library and sequenced. The analyzed results were sorted using Populus trichocarpa as a reference genome. Overall, 58,040 aligned single-nucleotide polymorphism (SNP) markers were identified, 17,755 of which were used for mapping genetic linkages. The genetic linkage map was divided into 19 linkage groups, with a total length of 2,129.54 cM. The analysis failed to identify any growth-related QTLs, but a gene assumed to be related to recovery from insect damage was identified on linkage group (chromosome) 4 through genome-wide association study.