• Genomics & Informatics
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• 제17권4호
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• pp.48.1-48.6
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• 2019

Over the last decade, genome-wide association studies (GWASs) have provided an unprecedented amount of genetic variations that are associated with various phenotypes. However, previous GWAS were mostly conducted in European populations, and these biased results for non-Europeans may result in a significant reduction in risk prediction for non-Europeans. An issue with the early GWAS was the winner's curse problem, which led to misleading results when constructing the polygenic risk scores (PRS). Therefore, more non-European population-based studies are needed to validate reported variants and improve genetic risk assessment across diverse populations. In this study, we validated 422 variants independently associated with glycemic indexes, liver enzymes, and type 2 diabetes in 125,872 samples from a Korean population, and further validated the results by assessing publicly available summary statistics from European GWAS (n = 898,130). Among the 422 independently associated variants, 284, 320, and 361 variants were replicated in Koreans, Europeans, and either one of the two populations. In addition, the effect sizes for Koreans and Europeans were moderately correlated (r = 0.33-0.68). However, 61 variants were not replicated in both Koreans and Europeans. Our findings provide valuable information on effect sizes and statistical significance, which is essential to improve the assessment of disease risk using PRS analysis.

• 말소리와 음성과학
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• 제2권3호
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• pp.65-73
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• 2010

No systematic study has examined the relationship between acoustic variability and /w/-deletion in Korean. Most previous studies on /w/-deletion have described /w/-variants in categorical terms, i.e., /w/-deletion or a full glide (Silva 1991; Kang 1997; Yun 2005). These studies are based either on impressionistic judgements without a systematic acoustic analysis or on an exclusive examination of internal acoustic variability of /w/ such as F2, without examining the availability of external acoustic cues such as voice onset time (VOT) of a consonant. However, given the important influence of the adjacent sounds for segmental realizations, it is necessary to examine possible acoustic variability in the differentiation of /w/-variants. The present study aims to address this issue by evaluating the acoustic properties of /CwV/, including VOT and formant transitions. In the analysis, 432 tokens in word-initial position (216 /CwV/ words and 216 /CV/ words) were examined. The results indicated that /w/ exhibits four different variants. Firstly, /w/ is realized as a full glide. Such a variant is characterized by a VOT difference and significant differences in F1 and F2 at voicing onset compared with /CwV/ and /CV/. Secondly, /w/ can be maintained but coarticulated with the following vowel. Such a variant is demonstrated by differences in VOT and F2. Thirdly, /w/ is categorically deleted, which is indicated by the absence of any differences in VOT, F1, and F2. Fourthly, /w/ overlaps a consonant. The F2 difference without VOT difference is manifested in the variant. In contrast to VOT, F1, and F2 differences, pitch plays little role in determining /w/-variants in Korean. These findings suggest that allophones can be produced along a gradient continuum of acoustic cues, exhibiting sounds intermediate between the full realization of a given category and its deletion. Furthermore, each variant can be cued by a set of internal and external acoustic cues.

• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.259-265
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• 2013

The anti-apoptotic effect of (-)-epigallocatechin-3-gallate (EGCG) during unilateral testicular torsion and detorsion (TT/D) was established in our previous study. In mice, the smallest inhibitor of apoptosis, survivin, is alternatively spliced into three variants, each suggested to have a unique function. Here, we assessed how EGCG exerts its protective effect through the expression of the different survivin splice variants and determined its effect on the morphology of the seminiferous tubules during TT/D. Three mouse groups were used: sham, TT/D+vehicle and TT/D treated with EGCG. The expression of the survivin variants (140 and 40) and other apoptosis genes (p53, Bax and Bcl-2) was measured with semi-quantitative RT-PCR. Histological analysis was performed to assess DNA fragmentation, damage to spermatogenesis and morphometric changes in the seminiferous tubules. In the TT/D+vehicle group, survivin 140 expression was markedly decreased, whereas survivin 40 expression was not significantly different. In parallel, there was an increase in the mRNA level of p53 and the Bax to Bcl-2 ratio in support of apoptosis induction. Histological analyses revealed increased DNA fragmentation and increased damage to spermatogenesis associated with decreased seminiferous tubular diameter and decreased germinal epithelial cell thickness in the TT/D+vehicle group. These changes were reversed to almost sham levels upon EGCG treatment. Our data indicate that EGCG protects the testis from TT/D-induced damage by protecting the morphology of the seminiferous tubules and modulating survivin 140 expression.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제42권5호
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• pp.278-283
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• 2016

Objectives: The maxillary sinus mucosa is reported to recover to preoperative sterility after sinus floor elevation. However, when drainage of maxillary sinus is impaired, recovery can be delayed and maxillary sinusitis can occur. Therefore, in this study, we investigated the correlations between anatomic variants that can interrupt the ostium of the maxillary sinus and incidence of complication after sinus lifting. Materials and Methods: The subjects are 81 patients who underwent sinus lifting in Wonkwang University Dental Hospital (Iksan, Korea). Computed tomography (CT) images of the subjects were reviewed for presence of nasal septum deviation, anatomic variants of the middle turbinate, and Haller cells. Correlations between anatomic variations and occurrence of maxillary sinusitis were statistically analyzed. Results: Patients with anatomic variants of ostio-meatal units, such as deviated nasal septum, concha bullosa or paradoxical curvature of the middle turbinate, or Haller cells, showed a higher rate of complication. However, only presence of Haller cell showed statistically significant. Conclusion: Before sinus lifting, CT images are recommended to detect anatomic variants of the ostio-meatal complex. If disadvantageous anatomic variants are detected, the use of nasal decongestants should be considered to reduce the risk of postoperative sinusitis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4239-4242
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• 2013

It is reported that the expression level of MLL3 in gastric cancer tissue highly correlates with tumor progression. However, whether MLL3 genetic variants are associated with the risk of gastric cancer remains unclear. In this study, we conducted a genotyping analysis for MLL3 in 314 cases of gastric cancer and 322 controls from the Chinese Han population. 4 SNPs (rs6943984, rs4725443, rs3800836, rs6464211) were selected for the present analysis. We found 2 SNPs (rs6943984, rs4725443) of MLL3 gene were significantly associated with the risk of gastric cancer : the rs6943984 with the minor allele A and rs4725443 with the minor allele C revealed strong associations with increased gastric cancer risk [P < 0.001, OR=1.97, 95% CI=1.48~2.64 and P <0.001, OR=2.23, 95% CI=1.54~3.24]. Haplotype analysis of the four SNPs showed that haplotype A-T-A-C, G-T-G-C, and G-C-A-C increased the risk of gastric cancer (P <0.001, P=0.18, and P<0.001, respectively), while haplotype G-T-A-C significantly reduced the risk of gastric cancer (P <0.001). We concluded that MLL3 variants are significantly associated with gastric cancer risk. Our results for the first time provided new insight into susceptibility factors of MLL3 gene variants in carcinogenesis of gastric cancer of the Chinese Han population.

• Toxicological Research
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• 제27권1호
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• pp.25-29
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• 2011

The cytochrome P450 (P450, CYP) are the superfamily of heme-containing monooxygenase enzymes, found throughout all nature including mammals, plants, and microorganisms. Mammalian P450 enzymes are involved in oxidative metabolism of a wide range of endo- and exogenous chemicals. Especially P450s involved in drug metabolisms are important for drug efficacy and polymorphisms of P450s in individuals reflect differences of drug responses between people. To study the functional differences of CYP2A6, CYP2D6, and CYP4A11 variants, we cloned the four CYP2A6, three CYP2D6, and three CYP4A11 variants, which were found in Korean populations, in mammalian expression vector pcDNA by PCR and examined their expressions in COS-7 mammalian cells using immunoblots using P450 specific polyclonal antibodies. Three of four CYP2A6, two of three CYP4A11, and two of three CYP2D6 variants showed expressions in COS-7 cells but the relative levels of expressions are remarkably different in those of each variants. Our findings may help to study and explain the differences between functions of CYP variants and drug responses in Korean populations.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1987-1991
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• 2016

Breast cancer has emerged as the most prevalent cancer among women worldwide, including in Indonesia. The contribution of genes associated with high-risk breast-ovarian cancers, BRCA1 and BRCA2, in the Indonesian population is relatively unknown. We have characterized family history of patients with moderate- to high-risk of breast cancer predisposition in 26 unrelated cases from Indonesia for BRCA1/2 mutation analyses using direct sequencing. Known deleterious mutations were not found in either BRCA1 or BRCA2 genes. Seven variants in BRCA2 were documented in 10 of 26 patients (38%). All variants were categorized as unclassified (VUSs). Two synonymous variants, c.3623A>G and c.4035T>C, were found in 5 patients. One variant, c4600T>C, was found in a 38 year old woman with a family history of breast cancer. We have found 4 novel variants in BRCA2 gene including c.6718C>G, c.3281A>G, c.10176C>G, and c4490T>C in 4 unrelated patients, all of them having a positive family history of breast cancer. In accordance to other studies in Asian population, our study showed more frequent variants in BRCA2 compared to BRCA1. Further studies involving larger numbers of hereditary breast cancer patients are required to reveal contribution of BRCA1/2 mutations and/or other predisposing genes among familial breast cancer patients in Indonesia.

• 한국음향학회지
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• 제20권2호
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• pp.35-43
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• 2001

음성 인식이나 음성 합성시 필요한 발음열을 수작업으로 작성할 경우 작성자의 음운변화 현상에 대한 전문적 언어지식을 비롯하여 많은 시간과 노력이 요구되며 일관성을 유지하기도 쉽지 않다. 또한 한국어의 음운 변화 현상은 단일 형태소의 내부와 복합어에서 결합된 형태소의 경계점, 여러 형태소가 결합해서 한 어절을 이룰 경우 그 어절 내부의 형태소의 경계점, 여러 어절이 한 어절을 이룰 때 구성 어절의 경계점에서 서로 다른 적용 양상을 보인다. 본 논문에서는 이러한 문제를 해결하기 위해서 형태음운론적 분석에 기반하여 문자열을 자동으로 발음열로 변환하는 발음 생성 시스템을 제안하였다. 이 시스템은 한국어에서 빈번하게 발생하는 음운변화 현상의 분석을 통해 정의된 음소 변동 규칙과 변이음 규칙을 다단계로 적용하여 가능한 모든 발음열을 생성한다. 각 음운변화 규칙을 포함하는 대표적인 언절 리스트를 이용하여 구성된 시스템의 안정성을 검증하였고, 발음사전 구성과 학습용 발음열의 유용성을 인식 실험을 통해 평가하였다. 그 결과 표제어 사이의 음운변화 현상을 반영한 발음사전의 경우 5-6％ 정도 나은 단어 인식률을 얻었으며, 생성된 발음열을 학습에 사용한 경우에서도 향상된 결과를 얻을 수 있었다.

• Genomics & Informatics
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• 제8권3호
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• pp.131-137
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• 2010

Genome-wide association studies (GWASs) have greatly contributed to the identification of common variants responsible for numerous complex traits. There are, however, unavoidable limitations in detecting causal and/or rare variants for traits in this approach, which depends on an LD-based tagging SNP microarray chip. In an effort to detect potential casual and/or rare variants for complex traits, such as type 2 diabetes (T2D) and triglycerides (TGs), we conducted a targeted resequencing of loci identified by the Korea Association REsource (KARE) GWAS. The target regions for resequencing comprised whole exons, exon-intron boundaries, and regulatory regions of genes that appeared within 1 Mb of the GWA signal boundary. From 124 individuals selected in population-based cohorts, a total of 0.7 Mb target regions were captured by the NimbleGen sequence capture 385K array. Subsequent sequencing, carried out by the Roche 454 Genome Sequencer FLX, generated about 110,000 sequence reads per individual. Mapping of sequence reads to the human reference genome was performed using the SSAHA2 program. An average of 62.2% of total reads was mapped to targets with an average 22X-fold coverage. A total of 5,983 SNPs (average 846 SNPs per individual) were called and annotated by GATK software, with 96.5% accuracy that was estimated by comparison with Affymetrix 5.0 genotyped data in identical individuals. About 51% of total SNPs were singletons that can be considered possible rare variants in the population. Among SNPs that appeared in exons, which occupies about 20% of total SNPs, 304 nonsynonymous singletons were tested with Polyphen to predict the protein damage caused by mutation. In total, we were able to detect 9 and 6 potentially functional rare SNPs for T2D and triglycerides, respectively, evoking a further step of replication genotyping in independent populations to prove their bona fide relevance to traits.

• Journal of Genetic Medicine
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• 제18권2호
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• pp.127-131
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• 2021

Autosomal recessive spinocerebellar ataxia 20 (SCAR20; OMIM #616354) is a recently described disorder that is characterized by ataxia, intellectual disability, cerebellar atrophy, macrocephaly, coarse face, and absent speech. It is caused by loss-of-function mutations in SNX14. To date, all cases with homozygous pathogenic variants have been identified in consanguineous families. This report describes the first Korean cases of SCAR20 family caused by homozygous variants in SNX14. Two siblings were referred to our clinic because of severe global developmental delay. They presented similar facial features, including a high forehead, long philtrum, thick lips, telecanthus, depressed nasal bridge, and broad base of the nose. Because the older sibling was unable to walk and newly developed ataxia, repeated brain magnetic resonance imaging (MRI) was performed at the age of 4 years, revealing progressive cerebellar atrophy compared with MRI performed at the age of 2 years. The younger sibling's MRI revealed a normal cerebellum at the age of 2 years. Whole-exome sequencing was performed, and homozygous variants, such as c.2746-2A>G, were identified in SNX14 from the older sibling. Sanger sequencing confirmed homozygous SNX14 variants in the two siblings as well as a heterozygous variant in both parents. This report extends our knowledge of the phenotypic and mutational spectrum of SCAR20. We also highlight the importance of deep phenotyping for the diagnosis of SCAR20 in individuals with developmental delay, ataxia, cerebellar atrophy, and distinct facial features.