• Genomics & Informatics
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• v.19 no.4
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• pp.37.1-37.7
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• 2021

Genome-wide association studies (GWASs) facilitated the discovery of countless disease-associated variants. However, GWASs have mostly been conducted in European ancestry samples. Recent studies have reported that these European-based association results may reduce disease prediction accuracy when applied in non-Europeans. Therefore, previously reported variants should be validated in non-European populations to establish reliable scientific evidence for precision medicine. In this study, we validated known associations with type 2 diabetes (T2D) and related metabolic traits in 125,850 samples from a Korean population genotyped by the Korea Biobank Array (KBA). At the end of December 2020, there were 8,823 variants associated with glycemic traits, lipids, liver enzymes, and T2D in the GWAS catalog. Considering the availability of imputed datasets in the KBA genome data, publicly available East Asian T2D summary statistics, and the linkage disequilibrium among the variants (r² < 0.2), 2,900 independent variants were selected for further analysis. Among these, 1,837 variants (63.3%) were statistically significant (p ≤ 0.05). Most of the non-replicated variants (n = 1,063) showed insufficient statistical power and decreased minor allele frequencies compared with the replicated variants. Moreover, most of known variants showed <10% genetic heritability. These results could provide valuable scientific evidence for future study designs, the current power of GWASs, and future applications in precision medicine in the Korean population.

• Genomics & Informatics
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• v.21 no.4
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• pp.48.1-48.8
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• 2023

Liver cancer is the fourth leading cause of death worldwide. Well-known risk factors include hepatitis B virus and hepatitis C virus, along with exposure to aflatoxins, excessive alcohol consumption, obesity, and type 2 diabetes. Genomic variants play a crucial role in mediating the associations between these risk factors and liver cancer. However, the specific variants involved in this process remain under-explored. This study utilized a bioinformatics approach to identify genetic variants associated with liver cancer from various continents. Single-nucleotide polymorphisms associated with liver cancer were retrieved from the genome-wide association studies catalog. Prioritization was then performed using functional annotation with HaploReg v4.1 and the Ensembl database. The prevalence and allele frequencies of each variant were evaluated using Pearson correlation coefficients. Two variants, rs2294915 and rs2896019, encoded by the PNPLA3 gene, were found to be highly expressed in the liver tissue, as well as in the skin, cell-cultured fibroblasts, and adipose-subcutaneous tissue, all of which contribute to the risk of liver cancer. We further found that these two SNPs (rs2294915 and rs2896019) were positively correlated with the prevalence rate. Positive associations with the prevalence rate were more frequent in East Asian and African populations. We highlight the utility of this population-specific PNPLA3 genetic variant for genetic association studies and for the early prognosis and treatment of liver cancer. This study highlights the potential of integrating genomic databases with bioinformatic analysis to identify genetic variations involved in the pathogenesis of liver cancer. The genetic variants investigated in this study are likely to predispose to liver cancer and could affect its progression and aggressiveness. We recommend future research prioritizing the validation of these variations in clinical settings.

• Journal of Animal Reproduction and Biotechnology
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• v.39 no.2
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• pp.138-144
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• 2024

Background: As the number of households raising companion dogs increases, the pet genetic analysis market also continues to grow. However, most studies have focused on specific purposes or native breeds. This study aimed to collect genomic data through single nucleotide polymorphism (SNP) chip analysis of companion dogs in South Korea and perform genetic diversity analysis and SNP annotation. Methods: We collected samples from 95 dogs belonging to 26 breeds, including mixed breeds, in South Korea. The SNP genotypes were obtained for each sample using an Axiom^TM Canine HD Array. Quality control (QC) was performed to enhance the accuracy of the analysis. A genetic diversity analysis was performed for each SNP. Results: QC initially selected SNPs, and after excluding non-diverse ones, 621,672 SNPs were identified. Genetic diversity analysis revealed minor allele frequencies, polymorphism information content, expected heterozygosity, and observed heterozygosity values of 0.220, 0.244, 0.301, and 0.261, respectively. The SNP annotation indicated that most variations had an uncertain or minimal impact on gene function. However, approximately 16,000 non-synonymous SNPs (nsSNPs) have been found to significantly alter gene function or affect exons by changing translated amino acids. Conclusions: This study obtained data on SNP genetic diversity and functional SNPs in companion dogs raised in South Korea. The results suggest that establishing an SNP set for individual identification could enable a gene-based registration system. Furthermore, identifying and researching nsSNPs related to behavior and diseases could improve dog care and prevent abandonment.

• Journal of Korean Society of Forest Science
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• v.80 no.2
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• pp.246-254
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• 1991

Genetic structure of a Pinus densiflora population consisting of two subpopulations on the north-and south-facing slopes of a mountain was studied by allozyme analysis. Allozyme variants in aspartate aminotransferase(AAT), glutmate dehydrogenase(GDH) and leucine aminopeptidase(LAP) systems are encoded, at least, by eight loci ; five for AAT, one for GDH and two for LAP. Average number of alleles examined over six loci was 3.33. Average heterozygosity and genetic diversity computed over six loci were, respectively, 0.19 and 2.76 for parental population, 0.17 and 2.22 for progeny population. Differences in allelic frequencies between maternal sources at many of the investigated loci were found and between subpopulations on the north- and south-facing slopes. Allele frequencies of maternal origin at some of the loci were significantly different from each other between the two subpopulations. Thus it appears that the matings within and between subpopulations were not random and the mountain ridge that divides the north-and south-facing slopes isolate the two suhpopulations reproductively to a great extent. Some of the genotypes both in parental and progeny(embryo) groups deviate significantly from the Hardy-Weinberg equilibrium state. It appears from the result that the pine population is originated from a few limited ancestral trees and thus consanguineous matings are prevalent in this pine population.

• Journal of Preventive Medicine and Public Health
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• v.44 no.3
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• pp.125-130
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• 2011

Objectives: The microRNA (miRNA) miR-196a2 may play an important role in lung cancer development and survival by altering binding activity of target mRNA. In this study, we evaluated their associations with the susceptibility of non-small cell lung cancers (NSCLC) by case-control study in a Korean population. Methods: We performed genotyping analyses for miR-196a2 rs11614913 T/C at miRNA regions in a case-control study using blood samples of 406 NSCLC patient and 428 cancer-free control groups. Results: The total C allele frequencies for miR-196a2 were 48.8% for the patients and 45.6% for the controls; and the genotype frequencies of TT, TC, and CC were 23.7%, 55.2%, and 21.1% for the patients and 31.1%, 46.35%, and 22.4% for the controls (p<0.05). Participants who possesses TC/CC genotypes showed high risk for NSCLC compared to those possessed TT genotypes (OR, 1.42; 95% CI, 1.03 to 1.96). The association was persisted in 60 and older age group, male, smokers, those without family history for cancer. However, no significant association of CC genotypes in recessive genetic model was observed. Conclusions: In conclusion, this case-control study provides evidence that miR-196a2 rs11614913 C/T polymorphisms are associated with a significantly increased risk of NSCLC in a dominant model, indicating that common genetic polymorphisms in miR-196a2 rs11614913 are associated with NSCLC. The association of miR196a2 rs11614913 polymorphisms and NSCLC risk require confirmation through additional larger studies.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9973-9978
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• 2014

Background: Hypoxia inducible factor-1 alpha (HIF-$1{\alpha}$) is the key regulator of cellular responses to hypoxia and plays a central role in tumour growth. Presence of Single nucleotide polymorphisms (SNPs) in the critical regulatory domains of HIF-$1{\alpha}$ may result in the overexpression of the protein and subsequent changes in the expression of the downstream target genes. The aim of study was to investigate the association of three SNPs (g.C111A, g.C1772T and g.G1790A) of HIF-$1{\alpha}$ with the risk of breast cancer in North Indian sporadic breast cancer patients. Materials and Methods: A total of 400 subjects, including 200 healthy controls and 200 patients with breast cancer were recruited in this study. Genotypes were determined using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. Results: The CC and CA genotype frequency of HIF-$1{\alpha}$ g.C111A polymorphism was 100 vs 99% and 0 vs 1% in breast cancer patients and healthy controls respectively. The frequencies of CC, CT and TT genotype of g.C1772T polymorphism were 76 vs 74.5%, 19 vs 21% and 5 vs 4.5% in breast cancer patients and control individuals respectively. There was no significant difference in genotype and allele frequencies of HIF-$1{\alpha}$ g.C1772T polymorphism between cases and control individuals (p>0.05). For g.G1790A genotypes, all patients and controls had only GG genotype. Conclusions: The three HIF-$1{\alpha}$ polymorphisms (g.C111A, g.C1772T and g.G1790A) are not associated with breast cancer risk in North-West Indian patients.

• Korean Journal of Biological Psychiatry
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• v.11 no.1
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• pp.26-32
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• 2004

Background:The dopaminergic genes have been implicated with some personality traits. Many recent studies indicated that there is a correlation between D2 dopamine receptor gene(DRD2) polymorphisms and the personality traits. The purpose of this study is to investigate a possible association between DRD2 gene (TaqI A, TaqI B) polymorphism and personality traits. Methods:The subjects were consisted of 173 blood-unrelated young female Koreans with a mean age(${\pm}SD$) of 13.88(${\pm}0.29$) years. These volunteers were recruited from one of the junior high schools in Seoul and were tested by the Korean version of the Temperament and Character Inventory(TCI). Genotyping of the DRD2 polymorphisms by PCR methods were carried out. Two DRD2 gene polymorphisms were classified and individually assessed as follows:TaqI A1+ vs A1-, TaqI B1+ vs B-. The associations between the TCI scores and TaqI A, TaqI B polymorphisms were assessed by Student's t-test. Results:In the 173 subjects, the allele frequencies of the DRD2 TaqI A1, TaqI B1 alleles ranged from 0.42 to 0.43, and these results are quite different from the ranges of 0.15-0.20 in the case of a Caucasian population. The genotype frequencies of DRD2(TaqI A1, TaqI B1) variants showed no significant deviation from the Hardy-Weinberg equilibrium. RD4(dependence vs. independence) of Cloninger's TCI, a sub-dimension of Reward Dependence, was significantly higher in the subjects having DRD2 less frequent alleles than those without these alleles. Conclusion:This study suggests that the female subjects carrying the less frequent DRD2 alleles exhibited higher reward-dependent personality trait compared to those without these alleles.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.8
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• pp.4559-4565
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• 2013

Background: Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA synthesis and repair. We here aimed to investigate two common polymorphisms, C677T and A1298C, with genotype and haplotype frequencies in colorectal cancer (CRC) cases among Jordanian. Materials and Methods: 131 CRC cases were studied for MTHFR C677T and A1298C polymorphisms, compared to 117 controls taken from the general population, employing the PCR-RFLP technique. Results: We found the frequency of the three different genotypes of MTHFR C677T among Jordanians to be CC: 61.7%, CT: 35.2%, and TT 3.1% among CRC cases and 50.9%, 38.8% and 10.3% among controls. Carriers of the TT genotype were less likely to have CRC (OR=0.25; 95%CI: 0.076-0.811; p=0.021) as compared to those with the CC genotype. Genotype analysis of MTHFR A12987C revealed AA: 38.9%, AC: 45%, and CC 16% among CRC cases and 37.4%, 50.4% and 12.2% among controls. There was no significant association between genetic polymorphism at this site and CRC. Haplotype analysis of MTHFR polymorphism at the two loci showed differential distribution of the TA haplotype (677T-1298A) between cases and controls. The TA haplotype was associated with a decreased risk for colorectal cancer (OR=0.6; 95% CI: 0.4-0.9, p=0.03). Conclusions: The genetic polymorphism of MTHFR at 677 and the TA haplotype may modulate the risk for CRC development among the Jordanian population. Our findings may reflect an importance of genes involved in folate metabolism in cancer risk.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.6
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• pp.775-778
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• 2006

Sarabi cows (n = 136) from the Sarabi Breeding Station were genotyped at bovine lymphocyte antigen (BoLA)-DRB3.2 locus by a genotyping system that used the polymerase chain reaction and restriction fragment length polymorphism. Genomic DNA was extracted from whole blood samples. A two-step polymerase chain reaction was carried out in order to amplify a 284 base-pair fragment of target gene. Nested-PCR products were digested with three restriction endonuclease enzymes RsaI, BstYI and HaeIII. Digested fragments were analyzed by polyacrylamide gel electrophoresis. Twenty-six BoLA-DRB3.2 alleles were identified with frequencies ranging from 0.4 to 15.1%. Six new allele types observed in this study have not been reported previously. Identified alleles include: BoLA-DRB3.$2^*1$, $^*2$, $^*4$, $^*6$, $^*8$, $^*12$, $^*13$, $^*14$, $^*15$, $^*16$, $^*17$, $^*23$, $^*24$, $^*25$, $^*28$, $^*32$, $^*34$, $^*35$, $^*36$, $^*37$, $^*42$, $^*46$, $^*51$, $^*kba$, $^*laa$ and $^*vaa$. Their frequencies were found to be 0.4, 0.4, 0.7, 11.4, 1.1, 1.8, 2.9, 2.2, 4.4, 9.6, 1.1, 13.6, 0.4, 0.4, 1.1, 0.7, 0.4, 6.2, 2.2, 3.7, 1.1, 7.7, 1.5, 15.1, 2.6 and 7.3% respectively. The six most frequent alleles (DRB3.2 $^*6$, $^*16$, $^*23$, $^*46$, $^*kba$ and $^*vaa$) accounted for 64.7% of the alleles in the population of this herd. Numerous studies on this locus, covering different breeds, has revealed the existence of various alleles in this locus, and new investigations have introduced novel alleles. With respect to the high number of the observed alleles in this survey and the novelty of some alleles with no previous record of reporting, it is plausible to conclude that the BoLA-DRB3.2 locus is highly polymorphic in Iranian native Sarabi cows.

• Journal of Animal Science and Technology
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• v.45 no.1
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• pp.13-22
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• 2003

Growth Hormone (GH) gene is a member of gene family through the evolutionary process from a small common ancestral gene by a series of gene duplications. The role of the GH in growth and performance controls has been extensively studied in human, mice and livestock. Many researchers have considered GH as a strong candidate gene for evaluation of genetic polymorphisms that could be associated with economic traits in cattle. We report here a novel missense mutation within the exon 5 of the bovine Growth Hormone (bGH) gene. We could amplified 522 bp fragments from eight unrelated Hanwoo cattle by PCR, then, subsequently cloned and sequenced. An Msp I RFLP corresponding to a C to T transition was observed at position 2258 nt. From this result, we could predict a missense mutation (Arg to Trp) at codon 166 in a highly conserved region among many mammals. Codominant Mendelian segregation of the two alleles, Msp I (+) and Msp I (－), was observed in two full-sib F2 families (n = 32, African taurine Bos taurus ${\times}$ African zebu Bos indicus) and eight half-sib Hanwoo families. For the availability of genetic marker, we have performed PCR-RFLP with a large number of individual animals from 15 different cattle breeds (European and Asian taurines, and African indicines). Consideration of breed frequencies of Msp I (－) allele in relation to breed type and their geographic origins, shows higher frequencies in humped breeds or Asian cattle breeds than in humpless or European breeds. This result indicates that the missense mutation can be contributed the functional significance such as the signal transduction through the receptor binding, also may be used as a marker for selection of the economic traits in Hanwoo.