• 생물정신의학
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• 제16권2호
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• pp.121-126
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• 2009

Objectives : The serotonin transporter gene(SLC6A4) is one of the most widely studied candidate genes in autism spectrum disorder(ASD), but there have been conflicting results from studies into the association between SLC6A4 and ASD. The aim of this study was to evaluate the association between single nucleotide polymorphisms(SNPs) in the SLC6A4 gene and ASD in the Korean population. Methods : We selected 12 SNPs in SLC6A4 and observed the genotype of 151 Korean ASD trios. We tested the family-based association for each individual polymorphism and haplotype by using the standard TDT method in Haploview(http://www.broad.mit.edu/mpg/haploview/). Results : Through transmission-disequilibrium testing and haplotype analysis, we could not find any statistically significant transmitted allele or haplotype. In addition, a case-control association test with Korean HapMap data did not reveal any statistical significance. Conclusion : Although serotonin-related genes must be considered candidate genes for ASD, we suggest that common SNPs of SLC6A4 are not important markers for associations with Korean ASD.

• The Korean Journal of Physiology and Pharmacology
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• 제12권3호
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• pp.125-129
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• 2008

The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of matrix metallopeptidase 2 (MMP2) are associated with obesity. MMP2 is an enzyme with proteolytic activity against matrix and nonmatrix proteins, particularly basement membrane constituents. To identify the relationship between polymorphisms of MMP2 and overweight/obese, we genotyped 5 SNPs (rs17242319, rs1053605, rs243849, rs2287074, and rs10775332) of the coding region of MMP2 using the Golden Gate assay on an Illumina BeadStation 500 GX. One hundred and forty two overweight/obese ($BMI\;{\ge}\;23$) and 145 normal (BMI 18 to < 23) subjects were analyzed. SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs were used for the analysis of genetic data. A linkage disequilibrium (LD) block was discovered among the 5 SNPs selected, including rs17242319, rs1053605, rs243849, and rs2287074. Of the 5 polymorphisms, 2 synonymous SNPs [rs17242319 (Gly226Gly) and rs10775332 (Phe602Phe)] were found significant associations with overweight/obese. Recently, rs1132896 replaced rs17242319 as a new number (SNP database, BUILD 129). In haplotype analysis using Haploview, a haplotype (haplotype: CCCA) containing a meaningful polymorphism (rs17242319) was found to be significantly different. The results suggest that MMP2 may be associated with overweight/obese in Korean population.

• Genomics & Informatics
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• 제6권3호
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• pp.130-135
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• 2008

The haplotypes of a 200 kb region in the human chromosome X terminal band (q28) were analyzed using the International HapMap Project Phasell data, which had been collected for three analysis panels (YRI, CEU, and CHB＋JPT). When multiple linkage disequilibrium blocks were encountered for a panel, the neighboring haplotypes that had crossover rate of 5% or more in the panel were combined to generate 'haploid' configurations. This resulted in 8, 7, and 5 'haploid' configurations for the panels of YRI, CEU, and CHB＋JPT, respectively. The multiple sequence alignment of these 'haploids' was used for the calculation of allele-sharing distances and the subsequent principal coordinate analysis. Two 'haploids' in CEU and CHB＋JPT were hypothesized as 'parental' in light of the observations that the successive recombinants of these haploids can model two other haploids in CEU and CHB＋JPT, and that their configurations were consistent with those in YRI. This study demonstrates the utility of haplotype phylogeny in understanding population evolution.

• 사물인터넷융복합논문지
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• 제4권2호
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• pp.21-28
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• 2018

본 연구에서는 ALK receptor tyrosine kinase (ALK) 유전자의 단일염기다형성이 뇌출혈의 발병에 관여하는 지를 연구하였다. 156명의 뇌출혈 환자와 425명의 정상인를 모집하였으며 네 개의 단일염기다형성에 대하여 상관성을 살펴보았다. 통계분석에서는 SNPstats, SPSS22.0, Haploview 프로그램을 활용하였다. Odd ratio, 95% 신뢰구간에서는 genotype 모델 및 allele 모델에서 계산하였다. 통계분석결과, rs1881421, rs1881420, rs3795850, rs2246745 의 단일염기다형성이 뇌출혈과 관련하여 유의성을 보였다. (rs1881421, OR=2.02, 95% CI=1.54-2.64, p<0.001; rs1881420, OR=0.53, 95% CI=1.16-2.01, p=0.003; rs3795850, OR=1.54, 95% CI=1.17-2.02, p=0.002; rs2246745, OR=1.95, 95% CI=1.46-2.60, p<0.001 in each allele analysis). CC, GT, and GC haplotypes 빈도 역시 유의성을 보였다. 네 개의 단일염기다형성의 minor allele 가 뇌출혈의 발병을 증가시키는데 기여하였다. 이러한 연구 결과는 ALK 유전자가 뇌출혈의 위험성과 관련 있음을 시사한다.

• Asian-Australasian Journal of Animal Sciences
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• 제31권5호
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• pp.643-649
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• 2018

Objective: POU class 1 homeobox 1 (POU1F1) mediates growth hormone expression and activity by altering transcription, eventually resulting in growth rate variations. Therefore, we aimed to identify chicken POU1F1 polymorphisms and evaluate the association between single nucleotide polymorphisms (SNPs) and growth-related traits, and logistic growth curve parameter traits (${\alpha}$, ${\beta}$, and ${\gamma}$). Methods: Three SNPs (M_1 to M_3) were used to genotype 585 $F_1$ and 88 $F_0$ birds from five Korean native chicken lines using a polymerase chain reaction-restriction fragment length polymorphism method. Results: Single marker analyses and traits association analyses showed that M_2 was significantly associated with body weight at two weeks, weight gain from hatch to 2 weeks, and weight gain from 16 to 18 weeks (p<0.05). M_3 was significantly associated with weight gain from 14 to 16 weeks and from 16 to 18 weeks, and asymptotic body weight (${\alpha}$) (p<0.05). No traits were associated with M_1. The POU1F1 haplogroups were significantly associated with weight gain from 14 to 16 weeks (p = 0.020). Linkage disequilibrium test and Haploview analysis shown one main haploblock between M_2 and M_3 SNP. Conclusion: Thus, POU1F1 significantly affects the growth of Korean native chickens and their growth curve traits.

• Genomics & Informatics
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• 제14권4호
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• pp.196-204
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• 2016

Many researchers have found that one of the most important characteristics of the structure of linkage disequilibrium is that the human genome can be divided into non-overlapping block partitions in which only a small number of haplotypes are observed. The location and distribution of haplotype blocks can be seen as a population property influenced by population genetic events such as selection, mutation, recombination and population structure. In this study, we investigate the effects of the density of markers relative to the full set of all polymorphisms in the region on the results of haplotype partitioning for five popular haplotype block partition methods: three methods in Haploview (confidence interval, four gamete test, and solid spine), MIG++ implemented in PLINK 1.9 and S-MIG++. We used several experimental datasets obtained by sampling subsets of single nucleotide polymorphism (SNP) markers of chromosome 22 region in the 1000 Genomes Project data and also the HapMap phase 3 data to compare the results of haplotype block partitions by five methods. With decreasing sampling ratio down to 20% of the original SNP markers, the total number of haplotype blocks decreases and the length of haplotype blocks increases for all algorithms. When we examined the marker-independence of the haplotype block locations constructed from the datasets of different density, the results using below 50% of the entire SNP markers were very different from the results using the entire SNP markers. We conclude that the haplotype block construction results should be used and interpreted carefully depending on the selection of markers and the purpose of the study.

• Journal of Korean Neurosurgical Society
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• 제49권1호
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• pp.8-12
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• 2011

Objective: Ossification of the posterior longitudinal ligament (OPLL) has a strong genetic component. Specific gene polymorphisms may be associated with OPLL in several genes which regulate calcification in chondrocytes, change of extracellular collagen matrix and secretions of many growth factors and cytokines controlling bone morphogenesis. Toll-like receptor 5 (TLR5) may playa role in the pathogenesis of OPLL by intermediate nuclear factor-kappa B (NF-${\kappa}B$). The current study focused on coding single nucleotide polymorphisms (SNPs) of TLR5 for a case-control study investigating the relationship between TLR5 and OPLL in a Korean population. Methods: A total of 166 patients with OPLL and 231 controls were recruited for a case-control association study investigating the relationship between SNPs of TLR5 gene and OPLL. Four SNPs were genotyped by direct sequencing (rs5744168, rs5744169, rs2072493, and rs5744174). SNP data were analyzed using the SNPStats, SNPAnalyzer, Haploview, and Helixtree programs. Multiple logistic regression analysis with adjustment for age and gender was performed to calculate an odds ratio (OR). Results: None of SNPs were associated with OPLL in three alternative models (codominant, dominant, and recessive models; p> 0.05). A strong linkage disequilibrium block, including all 4 SNPs, was constructed using the Gabriel method. No haplotype was significantly associated with OPLL in three alternative models. Conclusion: These results suggest that Toll-like receptor 5 gene may not be associated with ossification of the posterior longitudinal ligament risk in Korean population.

• Molecular & Cellular Toxicology
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• 제5권2호
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• pp.160-164
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• 2009

Notch signaling plays a crucial role in development of the nervous system. Neurodevelopmental hypothesis on etiology of schizophrenia has been implicated. The aim of this study is to determine whether single nucleotide polymorphisms (SNPs) of Notch homolog 4 (Drosophila) (NOTCH4) gene are associated with schizophrenia. This study included 283 schizophrenia patients diagnosed according to DSM-IV and 301 normal control subjects. Control subjects without history of psychiatric disorders were recruited. Four missense SNPs [rs915894 (exon 3, Lys117Gln), rs2071282 (exon 4, Pro204Leu), rs422951 (exon 6, Thr320Ala), and rs17604492 (exon 18, Gly942Arg)] of NOTCH4 gene were genotyped by the direct sequencing method. Multiple logistic regression models (codominant, dominant, and recessive models) were employed to evaluate odds ratio, 95% confidence interval, and p value. For analysis of genetic data, SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs were also used. Of 4 SNPs, rs2071282 was weekly associated with schizophrenia in two alternative models (codominant model, P=0.049; dominant, P=0.041). However, these associations were not significant after Bonferroni correction. At 4 SNPs, one linkage disequilibrium (LD) block was made. This block consisted of rs915894 and rs2071282. In haplotype analysis, AC haplotype was weakly associated with schizophrenia (dominant, P=0.04). This association was disappeared after Bonferroni correction. Our result shows possibility that some SNPs of NOTCH4 gene may be weekly associated with development of schizophrenia in Korean population. However, replication result by other population will be needed.

• Journal of Korean Neurosurgical Society
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• 제52권1호
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• pp.7-13
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• 2012

Objective : The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of fibroblast growth factor (FGF) 2 gene and fibroblast growth factor receptor (FGFR) genes are associated with ossification of the posterior longitudinal ligament (OPLL). Methods : A total of 157 patients with OPLL and 222 controls were recruited for a case control association study investigating the relationship between SNPs of FGF2, FGFR1, FGFR2 and OPLL. To identify the association among polymorphisms of FGF2 gene, FGFR1, FGFR2 genes and OPLL, the authors genotyped 9 SNPs of the genes (FGF2 : rs1476217, rs308395, rs308397, and rs3747676; FGFR1 : rs13317 and rs2467531; FGFR2 : rs755793, rs1047100, and rs3135831) using direct sequencing method. SNPs data were analyzed using the SNPStats, SNPAnalyzer, Haploview, and Helixtree programs. Results : Of the SNPs, a SNP (rs13317) in FGFR1 was significantly associated with the susceptibility of OPLL in the codominant (odds ratio=1.35, 95% confidence interval=1.01-1.81, p=0.048) and recessive model (odds ratio=2.00, 95% confidence interval=1.11-3.59, p=0.020). The analysis adjusted for associated condition showed that the SNP of rs1476217 (p=0.03), rs3747676 (p=0.01) polymorphisms in the FGF2 were associated with diffuse idiopathic skeletal hyperostosis (DISH) and rs1476217 (p=0.01) in the FGF2 was associated with ossification of the ligament flavum (OLF). Conclusion : The results of the present study revealed that an FGFR1 SNP was significantly associated with OPLL and that a SNP in FGF2 was associated with conditions that were comorbid with OPLL (DISH and OLF).

• Asian-Australasian Journal of Animal Sciences
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• 제32권3호
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• pp.341-349
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• 2019

Objective: Internal organs indirectly affect economic performance and well-being of animals. Study of internal organs during later layer period will allow full utilization of layer hens. Hence, we conducted a genome-wide association study (GWAS) to identify potential quantitative trait loci or genes that potentially contribute to internal organ weight. Methods: A total of 1,512 chickens originating from White Leghorn and Dongxiang Blue-Shelled chickens were genotyped using high-density Affymetrix 600 K single nucleotide polymorphism (SNP) array. We conducted a GWAS, linkage disequilibrium analysis, and heritability estimated based on SNP information by using GEMMA, Haploview and GCTA software. Results: Our results displayed that internal organ weights show moderate to high (0.283 to 0.640) heritability. Variance partitioned across chromosomes and chromosome lengths had a linear relationship for liver weight and gizzard weight ($R^2=0.493$, 0.753). A total of 23 highly significant SNPs that associated with all internal organ weights were mainly located on Gallus gallus autosome (GGA) 1 and GGA4. Six SNPs on GGA2 affected heart weight. After the final analysis, five top SNPs were in or near genes 5-Hydroxytryptamine receptor 2A, general transcription factor IIF polypeptide 2, WD repeat and FYVE domain containing 2, non-SMC condensin I complex subunit G, and sonic hedgehog, which were considered as candidate genes having a pervasive role in internal organ weights. Conclusion: Our findings provide an understanding of the underlying genetic architecture of internal organs and are beneficial in the selection of chickens.