• Journal of Genetic Medicine
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• 제20권1호
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• pp.1-5
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• 2023

Until now, rare disease studies have mainly been carried out by detecting simple variants such as single nucleotide substitutions and short insertions and deletions in protein-coding regions of disease-associated gene panels using diagnostic next-generation sequencing in association with patient phenotypes. However, several recent studies reported that the detection rate hardly exceeds 50% even when whole-exome sequencing is applied. Therefore, the necessity of introducing whole-genome sequencing is emerging to discover more diverse genomic variants and examine their association with rare diseases. When no diagnosis is provided by whole-genome sequencing, additional omics techniques such as RNA-seq also can be considered to further interrogate causal variants. This paper will introduce a description of these multi-omics techniques and their applications in rare disease studies.

• 대한의생명과학회지
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• 제25권2호
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• pp.190-195
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• 2019

Hemoglobin (Hb) concentrations and hematocrit (Hct) values can be changed by factors such as erythrocyte production, destruction, and bleeding. In addition, variants in the protein expression involved in the amount of red blood cells that determine Hb metabolism or Hct value can increase susceptibility to complex blood diseases. Previous studies have reported significant single nucleotide polymorphisms (SNPs) by applying a genome-wide association study (GWAS) on Hb levels and Hct values in European population. In this study, we confirmed whether the significant SNPs are replicated in Koreans. In previous studies, 26 and 18 SNPs with a significant correlation Hb and Hct were identified in Korean genotype data, and 21 and 12 SNPs were selected, respectively. The SNPs of PRKCE (rs10495928), TMPRSS6 (rs2235321, rs5756505, rs855791) were significantly associated with Hb (P<0.05). In the association analysis of Hct, the SNPs of HBS1L (rs6920211, rs9389268, rs9483788), PRKCE (rs4953318), SCGN (rs9348689) and TMPRSS6 (rs2413450) genes showed a significant correlation (P<0.05). Replicated SNPs and not replicated SNPs showed the difference of genetic distance calculated by Fst. The replicated SNPs with a significant correlation showed similar allele frequencies, whereas the not replicated SNPs showed a large difference in allele frequency. All replicated SNPs with significant correlations had Fst values less than 0.05, indicating that the genetic distance between the groups was close. On the other hand, the not replicated SNPs showed that the Fst value was 0.05 or more and the genetic distance was relatively large.

• Asian-Australasian Journal of Animal Sciences
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• 제32권2호
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• pp.176-182
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• 2019

Objective: This study was conducted to investigate basic information on genetic structure and characteristics of Limousin population in Hungary. Obtained results will be taken into consideration when adopting the new breeding strategy by the Association of Hungarian Limousin and Blonde d'Aquitaine Breeders (AHLBB). Methods: Genetic diversity and phylogenetic relationship of 3,443 Limousin cattle from 16 different herds were investigated by performing genotyping using 18 microsatellite markers. Amplified DNA was genotyped using an automated genetic analyzer. Results: Mean of effective alleles ($n_e$) of the populations was 3.77. Population C had the lowest number of effective alleles (3.01) and the lowest inbreeding coefficient ($F_{IS}$) value (-0.15). Principal component analysis of estimated genetic distance ($F_{ST}$) values (p<0.000) revealed two herds (C and E) distinct from the majority of other Limousin herds. The pairwise $F_{ST}$ values of population C compared to the others (0.066 to 0.120) fell into the range of moderate genetic distance: 0.050 to 0.150, while population E displayed also moderate genetic distance ($F_{ST}$ values in range 0.052 to 0.064) but only to six populations (G, H, J, L, N, and P). $F_{ST(C-E)}$ was 0.148, all other pairs -excluding C and E herds- displayed low genetic distance ($F_{ST}$<0.049). Population D, F, I, J, K, L, N, O, and P carried private alleles, which alleles belonged to 1.1% of the individuals. Most probable number of clusters (K) were 2 and 7 determined by Structure and BAPS software. Conclusion: This study showed useful genetic diversity and phylogenetic relationship data that can be utilized for the development of a new breeding strategy by AHLBB. The results presented could also contribute to the proper selection of animals for further whole genome scan studies of Limousins.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2231-2235
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• 2015

Genome-wide association studies (GWASs) of the entire genome provide a systematic approach for revealing novel genetic susceptibility loci for breast cancer. However, genetic association studies have hitherto been primarily conducted in women of European ancestry. Therefofre we here performed a pilot GWAS with a single nucleotide polymorphism (SNP) array 5.0 platform from $Affymetrix^{(R)}$ that contains 443,813 SNPs to search for new genetic risk factors in 89 breast cancer cases and 46 healthy women of Indonesian ancestry. The case-control association of the GWAS finding set was evaluated using PLINK. The strengths of allelic and genotypic associations were assessed using logistic regression analysis and reported as odds ratios (ORs) and P values; P values less than $1.00{\times}10^{-8}$ and $5.00{\times}10^{-5}$ were required for significant association and suggestive association, respectively. After analyzing 292,887 SNPs, we recognized 11 chromosome loci that possessed suggestive associations with breast cancer risk. Of these, however, there were only four chromosome loci with identified genes: chromosome 2p.12 with the CTNNA2 gene [Odds ratio (OR)=1.20, 95% confidence interval (CI)=1.13-1.33, $P=1.08{\times}10^{-7}$]; chromosome 18p11.2 with the SOGA2 gene (OR=1.32, 95%CI=1.17-1.44, $P=6.88{\times}10^{-6}$); chromosome 5q14.1 with the SSBP2 gene (OR=1.22, 95%CI=1.11-1.34, $P=4.00{\times}10^{-5}$); and chromosome 9q31.1 with the TEX10 gene (OR=1.24, 95%CI=1.12-1.35, $P=4.68{\times}10^{-5}$). This study identified 11 chromosome loci which exhibited suggestive associations with the risk of breast cancer among Indonesian women.

• 한국유전체학회:학술대회논문집
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• 한국유전체학회 2005년도 The 14th Korea Genome Conference
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• pp.24-24
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• 2005

• Asian-Australasian Journal of Animal Sciences
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• 제15권8호
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• pp.1222-1226
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• 2002

Estimates of genetic correlation between direct and maternal effects for weaning weight of beef cattle are often negative in field data. The biological existence of this genetic antagonism has been the point at issue. Some researchers perceived such negative estimate to be an artifact from poor modeling. Recent studies on sources affecting the genetic correlation estimates are reviewed in this article. They focus on heterogeneity of the correlation by sex, selection bias caused from selective reporting, selection bias caused from splitting data by sex, sire by year interaction variance, and sire misidentification and inbreeding depression as factors contributing sire by year interaction variance. A biological justification of the genetic antagonism is also discussed. It is proposed to include the direct-maternal genetic covariance in the analytical models.

• Toxicological Research
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• 제20권4호
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• pp.299-305
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• 2004

Adult periodontitis (AP) is a chronic inflammatory disease whose etiology is not well defined. Some studies suggested that the clinical characteristics of this disease may be in part explained by genetic factors, and some attempts to find genetic markers for this disease were successful. The interleukin-1 (IL-1) gene family as one of genetic factors may influence the expression of adult periodontitis. The aim of present study is to investigate the frequencies of genetic polymorphisms in the IL-1 gene family encoding three genes (IL-1A, IL-1B and IL-1RN) in Korean AP patients and periodontically healthy controls. There were no significant differences in genotype and allele frequencies of these polymorph isms between two groups, respectively. However, -511 polymorphism of IL-1 B gene was significantly associated with mean pocket depth (MPD, mm) value in AP patients (P<0.05). Therefore, our results suggest that -511 polymorphism in the IL-1B gene may be useful as a genetic marker for the severity of AP in Koreans.

• Asian-Australasian Journal of Animal Sciences
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• 제21권2호
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• pp.177-180
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• 2008

In this study, cattle microsatellite markers recommended for diversity studies of cattle by the EU AIRE 2066 Concerted Action Group were used to study the genetic diversity of 105 Thai swamp buffalo which were randomly selected from eight different research stations of the Department of Livestock Development, Thailand. Of 34 primer pairs, 16 were successfully amplified while the rest showed non-specific amplification. The lowest number of alleles was two while the highest was nine, with an average of 4.7 alleles per locus. The average unbiased heterozygosity for all eight populations was 0.5233, with a low of 0.4772 (Samui) and a high of 0.5616 (Burirum). The genetic distance ranged from 0.0574 to 0.2575. Populations from Lopburi and Burirum showed the closest relationship, whereas Srisagat and Samui were the most divergent. The results generated with the primers recommended by the EU AIRE 2066 Concerted Action Group are at a slight variance from our previous study, possibly as a result of the number of specific amplification products obtained, suggesting that cattle markers may not be optimal for studies of the genetic diversity of the Thai swamp buffalo.

• Genomics & Informatics
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• 제5권2호
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• pp.56-60
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• 2007

Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common craniofacial birth defect that is the result of a mixture of genetic and environmental factors. While studies have identified a number of different candidate genes and loci for the etiology of CL/P, the results have not been consistent among different ethnic groups. To study the genetic association of the candidate genes in Korean patients affected by CL/P, we genotyped 97 nonsyndromic CL/P patients and 100 control individuals using single nucleotide polymorphic markers at the MTHFR, TGFA, and IRF6 genes. We report that the T3827C marker at TGFA showed significant association with nonsyndromic CL/P, but all the other markers tested were not significantly associated with nonsyndromic CL/P in Korean patients.

• Asian Pacific Journal of Cancer Prevention
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• 제13권1호
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• pp.111-115
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• 2012

Variants of X-ray repair cross-complementing group 1 (XRCC1) are involved in the development of cancer, but studies investigating the association of XRCC1-77T>C polymorphism with cancer risk have reported conflicting results. To clarify the effect of the XRCC1 -77T>C polymorphism on cancer risk, we performed a meta-analysis by conducting searches of the published literature in PubMed, Embase and CBM databases. Finally, 13 studies were included into our meta-analysis, involving a total of 11, 678 individuals. Subgroup analyses were performed by ethnicity and cancer type. The results of this meta-analysis showed that there was significant association between the C variant of XRCC1-77T>C polymorphism and cancer risk in all four genetic comparison models (ORC vs. T =1.19, 95%CI 1.07-1.31, P = 0.001; OR homozygote model =1.28, 95%CI 1.07-1.52, P = 0.007; OR recessive genetic model =1.22, 95%CI 1.04-1.44, P = 0.015; OR dominant model =1.21, 95% CI 1.07-1.35, P = 0.001). In the subgroup analyses based on ethnicity, the association was still significant in the Asian population (all p values<0.001), but not in the Caucasian population (all p values > 0.05). Thus, the XRCC1 -77T>C polymorphism is associated with cancer risk, and individuals with XRCC1 -77C variant have a significantly higher cancer risk, particularly in the Asian population.