• Genomics & Informatics
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• v.5 no.2
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• pp.61-67
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• 2007

The allele frequencies of markers as well as linkage disequilibrium (LD) can be changed in cases due to the LD between markers and the disease allele, exhibiting spurious associations of markers. To identify the true association, classical statistical tests for dealing with confounders have been applied to draw a conclusion as to whether the association of variants comes from LD with the known disease allele. However, a more direct test considering LD using estimated haplotype frequencies may be more efficient. The null hypothesis is that the different allele frequencies of a variant between cases and controls come solely from the increased disease allele frequency and the LD relationship with the disease allele. The haplotype frequencies of controls are estimated using the expectation maximization (EM) algorithm from the genotype data. The estimated frequencies are applied to calculate the expected haplotype frequencies in cases corresponding to the increase or decrease of the causative or protective alleles. The suggested method was applied to previously published data, and several APOE variants showed association with Alzheimer's disease independent from the APOE ${\varepsilon}4$ variant, rs429358, regardless of LD showing significant simulated p-values. The test results support the possibility that there may be more than one common disease variant in a locus.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2747-2751
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• 2014

Background: DNA repair pathways play a crucial role in maintaining the human genome. Previous studies associated DNA repair gene polymorphisms (XPD Lys751Gln, XRCC1 Arg280His and XRCC1 Arg399Gln) with nasopharyngeal carcinoma. These non-synonymous polymorphisms may alter DNA repair capacity and thus increase or decrease susceptibility. The present study aimed to determine the genotype distribution of XPD codon 751, XRCC1 codon 280 and codon 399 polymorphisms and haplotype associations among NPC cases and controls in the Malaysian population. Materials and Methods: We selected 157 NPC cases and 136 controls from two hospitals in Kuala Lumpur, Malaysia for this study. The polymorphisms studied were genotyped by PCR-RFLP assay and allele and genotype frequenci es, haplotype and linkage disequilibrium were determined using SNPstat software. Results: For the XPD Lys751Gln polymorphism, the frequency of the Lys allele was higher in cases than in controls (94.5% versus 85.0%). For the XRCC1 Arg280His polymorphism, the frequency of Arg allele was 90.0% and 89.0% in cases and controls, respectively and for XRCC1 Arg399Gln the frequency of the Arg allele was 72.0% and 72.8% in cases and controls respectively. All three polymorphisms were in linkage disequilibrium. The odds ratio from haplotype analysis for these three polymorphisms and their association with NPC was 1.93 (95%CI: 0.90-4.16) for haplotype CGC vs AGC allele combinations. The global haplotypte association with NPC gave a p-value of 0.054. Conclusions: Our study provides an estimate of allele and genotype frequencies of XRCC1Arg280His, XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms in the Malaysian population and showed no association with nasopharyngeal cancer.

• Korean Journal of Clinical Laboratory Science
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• v.56 no.3
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• pp.236-247
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• 2024

The human leukocyte antigen (HLA) system, which is part of the major histocompatibility complex (MHC) plays a vital role in immune responses by differentiating between itself and foreign cells and antigens. The significant diversity of alleles affects disease susceptibility and immune responses within different populations. Specifically, the HLA-A and HLA-DRB1 alleles are associated with various immune-related diseases, and understanding the frequency and haplotype associations of these alleles is vital for genetic and immunological research. To investigate the distribution of these characteristics in Koreans, we isolated peripheral blood mononuclear cells (PBMCs) from blood samples donated by volunteers at the Seoul Central Blood Bank and performed HLA typing on 790 samples. Our study found that the HLA-A and HLA-DRB1 alleles are widely distributed within the Korean population, with HLA-A^*24:02 (21.7%) and HLA-DRB1*09:01 (9.9%) being the most frequent. Significant haplotype associations between specific HLA-A and HLA-DRB1 alleles were identified using the Chi-square test, suggesting that certain genetic combinations may influence disease onset. This insight could contribute to the development of predictive and preventative strategies for various diseases. The unique genetic characteristics of the Korean population highlight the importance of studying the HLA allele and the haplotype distributions in this group as key indicators for understanding disease susceptibility.

• Genomics & Informatics
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• v.7 no.1
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• pp.1-12
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• 2009

An alternative way of constructing ancestral graphs, which is different from the coalescent-based approach, is proposed using population linkage disequilibrium (LD) data. The main difference from the existing method is the construction of the ancestral graphs based on variants instead of individual sequences. Therefore, the key of the proposed method is to use the order of allele ages in the graphs. Distinct from the previous age-estimation methods, allele ages are estimated from full haplotype information by examining the number of generations from the initial complete LD to the current decayed state for each two variants depending on the direction of LD decay between variants. Using a simple algorithmic procedure, an ancestral graph can be derived from the expected allele ages and current LD decay status. This method is different in many ways from previous methods, and, with further improvement, it might be a good replacement for the current approaches.

• Journal of Internet of Things and Convergence
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• v.4 no.2
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• pp.21-28
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• 2018

I investigated that ALK receptor tyrosine kinase (ALK) gene polymorphisms were contributed to susceptibility to ICH in Korean population. I recruited 156 ICH patients and 425 healthy controls for this study, respectively. rs1881421, rs1881420, rs3795850, and rs2246745 single nucleotide polymorphisms (SNPs) were genotyped. The genotype and allele distributions of tested four SNPs was analyzed using the SNPStats, SPSS 22.0, and the Haploview v.4.2 software. The Odd's ratios (OR), 95% confidence intervals (CI), and P values were calculated in allele and genotype models. I found that rs1881421, rs1881420, rs3795850, and rs2246745 SNPs of ALK gene (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). And distributions of CC, GT, and GC haplotypes between the ICH group and the control group also showed significant association with ICH (CC haplotype, p<0.001; GT haplotype, p=0.006; GC haplotype, p<0.001). These minor alleles of tested four SNPs in ALK gene were contributed to increased risk of development for ICH. Our findings suggested that the ALK gene may be a risk factor for susceptibility to ICH.The Korea Internet of Things Society.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3101-3109
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• 2015

Background: Methylenetetrahydrofolate reductase (MTHFR) is involved in amino acid synthesis and DNA function. Two common polymorphisms are reported, C677T and A1298C, that are implicated in a number of human diseases, including cancer. Objective: The association between MTHFR C677T and A1298C genotype and haplotype frequencies in risk for lung cancer (LC) was investigated in the Jordanian population. Materials and Methods: A total of 98 LC cases were studied for MTHFR C677T and A1298C polymorphisms, compared to 89 controls taken from the general population, employing the PCR-RFLP technique. Results: The frequency of the genotypes of MTHFR C677T among Jordanians was: CC, 59.6%, CT, 33%; and TT, 7.4% among LC cases and 49.4%, 40.2% and 10.3% among controls. No significant association was detected between genetic polymorphism at this site and LC. At MTHFR A12987C, the genotype distribution was AA, 29.5%; AC, 45.3%, and CC 25.3% among LC cases and 36.8%, 50.6% and 12.6% among controls. Carriers of the CC genotype were more likely to have LC (OR=2.5; 95%CI: 1.04-6; p=0.039) as compared to AA carriers. Smokers and males with the CC genotype were 9.9 and 6.7 times more likely to have LC, respectively ($OR_{smokers}=9.9$; 95%CI: 1.2-84.5, p=0.018; $OR_{men}=6.6$; 95%CI: 1.7-26.2, p=0.005). Haplotype analysis of MTHFR polymorphism at the two loci showed differential distribution of the CC haplotype (677C-1298C) between cases and controls. The CC haplotype was associated with an increased risk for lung cancer (OR=1.6; 95% CI: 1.03-2.4, p=0.037). Conclusions: The genetic polymorphism of MTHFR at 1298 and the CC haplotype (risk is apparently lower with the C allele at position 677) may modulate the risk for LC development among the Jordanian population. Risk associated with the 1298C allele is increased in smokers and in males. The results indicate that a critical gene involved in folate metabolism plays a modifying role in lung cancer risk, at least in the Jordanian population.

• Molecules and Cells
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• v.25 no.1
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• pp.20-29
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• 2008

Cytoplasmic male sterility (CMS), one of the most important traits in crop breeding, has been used for commercial seed production by $F_1$ hybrid cultivars of pepper (Capsicum annuum L.). To develop reliable molecular markers for allelic selection of the Restorer-of-fertility (Rf) gene, which is known to be a major determinant of pollen fertility restoration in peppers, a sequence of approximately 10 kb flanking an RAPD fragment closely linked to the Rf locus was obtained by genome walking. A homology search revealed that this sequence contained an LTR retrotransposon and a non-LTR LINE-like retrotransposon. Sequencing of this Rf-linked region to search for polymorphisms between a dominant and recessive allele revealed 98% nucleotide sequence identity between them. A third polymorphic haplotype of the Rf-linked sequence, which has 94-96% nucleotide sequence identity with the two previously isolated haplotypes, was identified among a large number of breeding lines. Utilizing polymorphic sequences in the haplotypes, PCR markers were developed for selection of particular haplotypes and used to examine the distribution of the haplotypes in diverse breeding lines, cultivars, and C. annuum germplasms. Surprisingly, the third haplotype was the predominant type in C. annuum germplasms, while its frequency in $F_1$ hybrid cultivars was relatively low. Meanwhile, analysis of breeding lines whose Rf allele genotypes and male-sterility phenotypes were already known revealed that the third haplotype was mainly present in exotic breeding lines that cause unstable male-sterility when combined with sterile cytoplasms.

• Genomics & Informatics
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• v.6 no.3
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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.

• Toxicological Research
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• v.18 no.3
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• pp.233-240
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• 2002

In view of the effect of $\beta_2$-Adrenergic receptors ($\beta_2$-AR) as a risk factor for essential hypertension, we investigated the Fnu4HI and MnlI RFLPs of $\beta_2$ -AR gene in the Korean patients with essential hypertension and normal controls. There were no significant differences in the allele and genotype of these polymorphisms between normotensive and essential hypertensive subjects. In ethnic comparison, the allele frequencies of these three sites contained Nde I RFLP reported the association with essential hypertension in Korean population previously, were very different from those of other ethnic populations studied. The significant linkage disequilibrium was detected only in hypertensive group between Nde I and Fnu4HI sites. The Fnu4HI RFLP was also significantly associated with plasma triglyceride (TG) level. Therefore, our results suggest that the significant association between Fnu4HI variation in the human $\beta_2$-AR gene and plasma TG level may reflect the potential role of human $\beta_2$-AR gene as one of the genetic components for cardiovascular risk.

• Horticultural Science & Technology
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• v.32 no.2
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• pp.210-216
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• 2014

The distribution of S-haplotypes and genetic relationships were evaluated for 47 accessions of 'Danji' radish (Raphanus sativus L. var. hortensis Baker f. gigantissimus Makino) originating from Jeju Island in South Korea. A total of 22 S-haplotype-specific SCAR markers for the S locus glycoprotein (SLG) and S receptor kinase (SRK) loci were tested, and six primer sets amplified locus-specific PCR fragments from at least one 'Danji' radish accession. S5 and S21 alleles atthe SLG locus were the most frequently distributed, and detected from 87.5% and 64.6% of the accessions, respectively. The frequency of the class-II haplotype at the SLG locus was 75%, more frequent than the class-I haplotype. The S23 allele at the SRK locus was detected from 7 accessions. Grouping of the accessions based on S-allele composition revealed three major groups, while 8 accessions showed a unique allelic composition. The genetic diversity of 47 'Danji' radishes and 1 'Gwandong' radish were also evaluated with 38 RAPD primers. A total of 312 bands were scored, and showed that 138 bands (44.2%) were monomorphic among the accessions, whereas 174 (55.8%) bands were polymorphic. Polymorphism rates ranged from 0.2 to 1.0, indicating significant variations in detecting polymorphism across RAPD primers. The genetic similarity coefficients among all pairs of the 48accessions varied from 0.62 to 0.93, and 42% of the comparisons exhibited values higher than 0.85. All the cultivars could be distinguished based on the DNA fingerprints revealed by RAPD. The comparisons between the dendrograms based on S-haplotypes and RAPDs indicate an unrelated and sporadic distribution for several accessions; however, there was a tendency for accessions with the same S-allelic composition to group into the same cluster.