• Asian-Australasian Journal of Animal Sciences
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• v.28 no.6
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• pp.771-781
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• 2015

Thoroughbred, a relatively recent horse breed, is best known for its use in horse racing. Although myostatin (MSTN) variants have been reported to be highly associated with horse racing performance, the trait is more likely to be polygenic in nature. The purpose of this study was to identify genetic variants strongly associated with racing performance by using estimated breeding value (EBV) for race time as a phenotype. We conducted a two-stage genome-wide association study to search for genetic variants associated with the EBV. In the first stage of genome-wide association study, a relatively large number of markers (~54,000 single-nucleotide polymorphisms, SNPs) were evaluated in a small number of samples (240 horses). In the second stage, a relatively small number of markers identified to have large effects (170 SNPs) were evaluated in a much larger number of samples (1,156 horses). We also validated the SNPs related to MSTN known to have large effects on racing performance and found significant associations in the stage two analysis, but not in stage one. We identified 28 significant SNPs related to 17 genes. Among these, six genes have a function related to myogenesis and five genes are involved in muscle maintenance. To our knowledge, these genes are newly reported for the genetic association with racing performance of Thoroughbreds. It complements a recent horse genome-wide association studies of racing performance that identified other SNPs and genes as the most significant variants. These results will help to expand our knowledge of the polygenic nature of racing performance in Thoroughbreds.

• Genomics & Informatics
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• v.21 no.3
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• pp.33.1-33.11
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• 2023

Type 2 diabetes mellitus (T2DM) is a multifactorial, polygenic, and metabolically complicated disease. A large number of genes are responsible for the biogenesis of T2DM and calpain10 (CAPN10) is one of them. The association of numerous CAPN10 genetic polymorphisms in the development of T2DM has been widely studied in different populations and noticed inconclusive results. The present study is an attempt to evaluate the plausible association of CAPN10 polymorphism SNP-19 (rs3842570) with T2DM and T2DM-related anthropometric and metabolic traits in the Noakhali region of Bangladesh. This case-control study included 202 T2DM patients and 75 healthy individuals from different places in Noakhali. A significant association (p < 0.05) of SNP-19 with T2DM in co-dominant 2R/3R vs. 3R/3R (odds ratio [OR], 2.7; p=0.0014) and dominant (2R/3R) + (2R/2R) vs. 3R/3R (OR, 2.47; p=0.0011) genetic models was observed. High-risk allele 2R also showed a significant association with T2DM in the allelic model (OR, 1.67; p=0.0109). The genotypic frequency of SNP-19 variants showed consistency with Hardy-Weinberg equilibrium (p > 0.05). Additionally, SNP-19 genetic variants showed potential associations with the anthropometric and metabolic traits of T2DM patients in terms of body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, and triglycerides. Our approach identifies the 2R/3R genotype of SNP-19 as a significant risk factor for biogenesis of T2DM in the Noakhali population. Furthermore, a large-scale study could be instrumental to correlate this finding in overall Bangladeshi population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.621-623
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• 2012

To estimate the genetic susceptibility for childhood lymphoma, we conducted an association study for 23 cases and 148 controls. Total 1536 tag single nucleotide polymorphisms (SNPs) were selected in 138 candidate gene regions related to immune responses, apoptosis, the cell cycle, and DNA repair. Twelve SNPs were significantly associated with the risk of lymphoma ($P_{trend}$ <0.05) in six genes ($IL1RN$, $IL2$, $IL12RB1$, $JAK3$, $TNFRSF13B$, and $XRCC3$). The most significant association was seen for $IL2$ variant rs2069762 ($OR_{TG+GG}$ vs. TT=3.43 (1.29-9.11), $P_{trend}$=0.002, min$P$=0.005). These findings suggest that common genetic variants in $IL2$ might play a role in the pathogenesis of childhood lymphoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2199-2206
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• 2012

Background: Our objective was to evaluate the MTHFR C677T-A1298C polymorphisms in patients with breast cancer and in individuals with no history of cancer, to compare the levels of genetic damage and apoptosis under folic acid (FA) deficiency between patients and controls, and to assess associations with breast cancer. Methods: Genetic damage was marked by micronucleated binucleated cells (MNBN) and apoptosis was estimated by cytokinesis-block micronucleus assay (CBMN). PCR-RFLP molecular analysis was carried out. Results: The results showed significant associations between the MTHFR 677TT or the combined MTHFR C677T-A1298C and breast cancer risk (OR = 2.51, CI = 0.85 to 7.37, p = 0.08; OR = 4.11, CI = 0.78 to 21.8, p < 0.001). The MNBN from the combined MTHFR C677T-A1298C was higher and the apoptosis was lower than that of the single variants (p < 0.05). At 15 to 60 nmol/L FA, the MNBN in cases with the TTAC genotype was higher than controls (p < 0.05), whereas no significant difference in apoptosis was found between the cases and controls after excluding the genetic background. Conclusions: Associations between the combined MTHFR C677T-A1298C polymorphism and breast cancer are possible from this study. A dose of 120 nmol/L FA could enhance apoptosis in cases with MTHFR C677T-A1298C. Breast cancer individuals with the TTAC genotype may be more sensitive to the genotoxic effects of FA deficiency than controls.

• Anxiety and mood
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• v.15 no.2
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• pp.122-126
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• 2019

Objective : Dynamic proteolysis, through the ubiquitin-proteasome system, is an important molecular mechanism for the constant regulation of synaptic plasticity and stress responses in humans. In this study, we examined whether genetic variants in the ubiquitin-specific peptidase (USP) genes were associated with psychological traits of resilience and susceptibility to neuropsychiatric disorders for each gender. Methods : A total of 344 Korean healthy youths (190 males, 154 females) were included in the study. A genotyping of rs2241646 of USP2 and rs346006 of USP46 was performed. The Connor-Davidson Resilience Scale and Brief Fear of Negative Evaluation Scale were administered for measuring trait resilience and social anxiety, respectively. The genetic associations of the USP variants were tested using multiple analyses of covariance with psychological traits as dependent variables after controlling for age in each gender. Results : For USP2 rs2241646, women with the TT genotype showed significantly higher resilience and lower social anxiety, as compared to those carrying the C allele. There were no associations between USP46 rs346005 and the psychological traits in both genders. Conclusions : The present study showed a possible genetic association between the USP2 rs2241646 and stress resilience and trait anxiety in women. The findings suggest that ubiquitin-proteasome system may be related to the resilience and susceptibility to stress-related neuropsychiatric disorders such as anxiety disorders, possibly through the regulation of dynamic proteolysis responses to stress.

• Journal of Microbiology and Biotechnology
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• v.33 no.12
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• pp.1587-1594
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• 2023

Since its first report in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a grave threat to public health. Virus-specific countermeasures, such as vaccines and therapeutics, have been developed and have contributed to the control of the viral pandemic, which has become endemic. Nonetheless, new variants continue to emerge and could cause a new pandemic. Consequently, it is important to comprehensively understand viral evolution and the roles of mutations in viral infectivity and transmission. SARS-CoV-2 beta variant encode mutations (D614G, N501Y, E484K, and K417N) in the spike which are frequently found in other variants as well. While their individual role in viral infectivity has been elucidated against various therapeutic antibodies, it still remains unclear whether those mutations may act additively or synergistically when combined. Here, we report that N501Y mutation shows differential effect on two therapeutic antibodies tested. Interestingly, the relative importance of E484K and K417N mutations in antibody evasion varies depending on the antibody type. Collectively, these findings suggest that continuous efforts to develop effective antibody therapeutics and combinatorial treatment with multiple antibodies are more rational and effective forms of treatment.

• Genomics & Informatics
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• v.14 no.4
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• pp.187-195
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• 2016

In genetic association studies with high-dimensional genomic data, multiple group testing procedures are often required in order to identify disease/trait-related genes or genetic regions, where multiple genetic sites or variants are located within the same gene or genetic region. However, statistical testing procedures based on an individual test suffer from multiple testing issues such as the control of family-wise error rate and dependent tests. Moreover, detecting only a few of genes associated with a phenotype outcome among tens of thousands of genes is of main interest in genetic association studies. In this reason regularization procedures, where a phenotype outcome regresses on all genomic markers and then regression coefficients are estimated based on a penalized likelihood, have been considered as a good alternative approach to analysis of high-dimensional genomic data. But, selection performance of regularization procedures has been rarely compared with that of statistical group testing procedures. In this article, we performed extensive simulation studies where commonly used group testing procedures such as principal component analysis, Hotelling's $T^2$ test, and permutation test are compared with group lasso (least absolute selection and shrinkage operator) in terms of true positive selection. Also, we applied all methods considered in simulation studies to identify genes associated with ovarian cancer from over 20,000 genetic sites generated from Illumina Infinium HumanMethylation27K Beadchip. We found a big discrepancy of selected genes between multiple group testing procedures and group lasso.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5625-5629
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• 2013

Occurrence of breast cancer is related to genetic as well as cultural, environmental and life-style factors. Variations in diversity of these factors among different ethnic groups and geographical areas emphasize the immense need for studies in all racial-ethnic populations. The incidence of breast cancer in Pakistan is highest in Asians after Jews in Israel and 2.5 times higher than that in neighboring countries like Iran and India, accounting for 34.6% of female cancers. The Pakistani population is deficient in information regarding breast cancer etiology and epidemiology, but efforts done so far had suggested consanguinity as a major risk factor for frequent mutations leading to breast cancer and has also shed light on genetic origins in different ethnic groups within Pakistan. World-wide research efforts on different ethnicities have enhanced our understanding of genetic predisposition to breast cancer but despite these discoveries, 75% of the familial risk of breast cancer remains unexplained, highlighting the fact that the majority of breast cancer susceptibility genes remain unidentified. For this purpose Pakistani population provides a strong genetic pool to elucidate the genetic etiology of breast cancer because of cousin marriages. In this review, we describe the known breast cancer predisposition factors found in the local Pakistani population and the epidemiological research work done to emphasize the importance of exploring factors/variants contributing to breast cance, in order to prevent, cure and decrease its incidence in our country.

• Korean Journal of Veterinary Research
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• v.49 no.3
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• pp.243-248
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• 2009

After the original identification of canine parvovirus (CPV) type 2 (CPV-2) in 1978, new antigenic variants such as CPV-2a, CPV-2b and CPV-2c have become widespread in the most countries. In this study, the genetic analysis of canine parvovirus was investigated in a total of 13 CPV vaccines, which have been licensed in Korea since late 1980s, and a field isolate of CPV from a dog with CPV infection clinical symptom. The partial VP2 gene of CPV was amplified and sequenced from 13 vaccine strains and one field isolate. The results showed that of the 13 vaccine strains, 10 strains belong to the CPV-2, 2 strains to CPV-2b, the remaining and one isolate to CPV-2a type, respectively. Several mutations of amino acids were detected at residues of the critical region of the commercial vaccine strains. These data suggest that new type of vaccines containing CPV-2a or CPV-2b/2c type may be required for the better prevention of new CPV infection in dog population in Korea, because CPV-2 contained in most licensed vaccines has been replaced by antigenic variants designated CPV-2a or CPV-2b/c in the worldwide dog population.

• Bulletin of the Korean Chemical Society
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• v.35 no.9
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• pp.2781-2786
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• 2014

Human ${\alpha}_1$-antitrypsin (${\alpha}_1$-AT) is a natural inhibitor of neutrophil elastases and has several dozens of genetic variants. Most of the deficient genetic variants of human ${\alpha}_1$-AT are unstable and cause pulmonary emphysema. However, the most clinically significant variant, Z-type ${\alpha}_1$-AT, exhibits retarded protein folding that leads to accumulation of folding intermediates. These aggregate within the endoplasmic reticulum (ER) of hepatocytes, subsequently causing liver cirrhosis as well as emphysema. Here, we studied the role of an ER folding assistant protein Cpr5p on Z-type ${\alpha}_1$-AT folding. Cpr5p was induced > 2-fold in Z-type ${\alpha}_1$-AT-expressing yeast cells compared with the wild type. Knockout of CPR5 exacerbated cytotoxicity of Z-type ${\alpha}_1$-AT, and re-introduction of CPR5 rescued the knockout cells from aggravated cytotoxicity caused by the ${\alpha}_1$-AT variant. Furthermore, Cpr5p co-immunoprecipitated with Z-type ${\alpha}_1$-AT and facilitated its protein folding. Our results suggest that protein-folding diseases may be suppressed by folding assistant proteins at the site of causal protein biosynthesis.