• 제목/요약/키워드: Genotype phenotype

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Heterogenous Clinical Manifestations in Adult Patients with Late Diagnosis of Glycogen Storage Disease type Ia (성인기에 진단된 당원병 제 Ia형의 다양한 임상 양상)

  • Kim, Yoo-Mi;Cheon, Chong Kun;Kim, Gu-Hwan;Yoo, Han-Wook
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.15 no.1
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    • pp.9-17
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    • 2015
  • Glycogen storage disease (GSD) type Ia is rare inborn metabolic disorder, caused by glucose-6-phosphatase deficiency. It characterized by hepatomegaly, hypoglycemia, lactic acidosis, hypertriglyceridemia, and hyperuricemia and it is usually manifested in the infantile period. In addition, it is also associated with growth failure, pubertal delay, anemia, platelet dysfunction, osteopenia, and pulmonary hypertension. Hepatocellular adenoma and renal dysfunction are frequent late complications. Delayed diagnosis and inappropriate therapy lead to many complications such as growth failure, osteoporosis, refractory gout, renal failure, hepatocellular carcinoma (HCC), and pulmonary hypertension. Here, two Korean sisters diagnosed with GSD Ia, aged 33 and 36 respectively, were described and compared to recent articles about four adults with late diagnosis of GSD Ia. One sister had typical manifestations of GSD Ia including short stature (height, 145 cm), multiple hepatic adenoma, chronic kidney disease stage IV, and severe osteoporosis, whereas the older sister had normal stature (162 cm), one tiny hepatic nodule, and normal renal function. Direct sequencing of G6PC in two sisters identified a homozygous splicing mutation, c.645G>T, which is a prevalent mutation in Korea. Interestingly, our cases and four adults from recent reports had asymptomatic mild hypoglycemia and various manifestations including renal failure, HCC, fatty liver, or uncontrolled hyperlipidemia. These adult cases represent not only heterogenous phenotype to genotype within family members with GSD Ia but also long-term complications such as gouty arthritis, renal failure, and osteoporosis in untreated adult GSD Ia patients. In addition, lactic academia and hypertriglyceridemia are good markers of GSD Ia to distinguish from metabolic disease.

Development of cell models for high-throughput screening system of Charcot-Marie-Tooth disease type 1

  • Choi, Yu-Ri;Jung, Sung-Chul;Shin, Jinhee;Yoo, So Young;Lee, Ji-Su;Joo, Jaesoon;Lee, Jinho;Hong, Young Bin;Choi, Byung-Ok
    • Journal of Genetic Medicine
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    • v.12 no.1
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    • pp.25-30
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    • 2015
  • Purpose: Charcot-Marie-Tooth disease (CMT) is a peripheral neuropathy mainly divided into CMT type 1 (CMT1) and CMT2 according to the phenotype and genotype. Although molecular pathologies for each genetic causative have not been revealed in CMT2, the correlation between cell death and accumulation of misfolded proteins in the endoplasmic reticulum (ER) of Schwann cells is well documented in CMT1. Establishment of in vitro models of ER stress-mediated Schwann cell death might be useful in developing drug-screening systems for the treatment of CMT1. Materials and Methods: To develop high-throughput screening (HTS) systems for CMT1, we generated cell models using transient expression of mutant proteins and chemical induction. Results: Overexpression of wild type and mutant peripheral myelin protein 22 (PMP22) induced ER stress. Similar results were obtained from mutant myelin protein zero (MPZ) proteins. Protein localization revealed that expressed mutant PMP22 and MPZ proteins accumulated in the ER of Schwann cells. Overexpression of wild type and L16P mutant PMP22 also reduced cell viability, implying protein accumulation-mediated ER stress causes cell death. To develop more stable screening systems, we mimicked the ER stress-mediated cell death in Schwann cells using ER stress inducing chemicals. Thapsigargin treatment caused cell death via ER stress in a dose dependent manner, which was measured by expression of ER stress markers. Conclusion: We have developed genetically and chemically induced ER stress models using Schwann cells. Application of these models to HTS systems might facilitate the elucidation of molecular pathology and development of therapeutic options for CMT1.

Changes in Carotenoid Contents of Colored Pumpkin (Cucurbita spp.) Germplasms (유색 호박 (Cucurbita spp.) 유전자원별 카로테노이드 대사체 분석)

  • Lee, Min-Ki;Cho, Soo-Yeon;Cho, Soo-Jung;Shin, Jae-Hyeong;Kim, Heon-Woong;Kim, Sang-Gyu;Ko, Ho-Cheol;Ro, Na-Young;Kim, Jung-Bong;Baek, Hyung-Jin
    • Korean Journal of Environmental Agriculture
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    • v.34 no.3
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    • pp.186-191
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    • 2015
  • BACKGROUND: Carotenoids which are a major source of vitamin A are contributed to have great potential role in anti-carcinogenic effects and eyesight. Carotenoids which can not synthesize in human body are required for food supply. The objectives of this study are to investigate compositions and contents of pumpkin (Cucurbita spp.) germplasms based on their pulp color. METHODS AND RESULTS: Carotenoids were extracted with 0.2% ascorbic acid in ethanol and saponified with 80% potassium hydroxide. Insoluble compounds were extracted into hexane. A total of nine carotenoids (three xanthophylls and six carotenes) were identified from pumpkin germplasms using HPLC equipped with photodiode array detector (450 nm). Especially, lutein and ${\beta}$-carotenes were major compound in germplasms. Among isomers of ${\beta}$-carotene, all-trans-${\beta}$-carotene (16-27% of total carotenoids) was predominant compositions. The mean of total carotenoid contents was showed as brown (286.1 mg/100 g dw) > dark green (217.0) > orange (153.4) > primrose (85.8) > dark yellow (80.3). On the basis of carotenoid information, PLS-DA score plots showed different patterns by cluster in pumpkin germplasms. It was considered that these differences of phenotype were relative closely to genotype. CONCLUSION: This study indicated that dark color of pumpkin pulp was presented in high-level of biological pigments. It may contribute to develop potentially beneficial functional food ingredients.

Genetic Stability of Magnaporthe oryzae during Successive Passages through Rice Plants and on Artificial Medium

  • Park, Sook-Young;Chi, Myoung-Hwan;Milgroom, Michael G.;Kim, Hyo-Jung;Han, Seong-Sook;Kang, Seog-Chan;Lee, Yong-Hwan
    • The Plant Pathology Journal
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    • v.26 no.4
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    • pp.313-320
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    • 2010
  • Genetic instability of the rice blast fungus Magnaporthe oryzae has been suggested as a major factor underlying the rapid breakdown of host resistance in the field. However, little information is available on the mechanism of genetic instability. In this study, we assessed the stability of repetitive DNA elements and several key phenotypic traits important for pathogenesis after serially transferring two isolates though rice plants and an artificial medium. Using isolate 70-15, we obtained a total of 176 single-spore isolates from 10 successive rounds of culturing on artificial medium. Another 20 isolates were obtained from germ tubes formed at the basal and apical cells of 10 three-celled conidia. Additionally, 60 isolates were obtained from isolate KJ201 after serial transfers through rice plants and an artificial medium. No apparent differences in phenotypes, including mycelial growth, conidial morphologies, conidiation, conidial germination, appressorium formation, and virulence, or in DNA fingerprints using MGR586, MAGGY, Pot2, LINE, MG-SINE and PWL2 as probes were observed among isolates from the same parent isolate. Southern hybridization and sequence analysis of two avirulence genes, AVR-Pita1 and AVR-Pikm, showed that both genes were also maintained stably during 10 successive generations on medium and plants. However, one reversible loss of restriction fragments was found in the telomere-linked helicase gene (TLH1) family, suggesting some telomere regions may be more unstable than the rest of the genome. Taken together, our results suggest that phenotype and genotype of M. oryzae isolates do not noticeably change, at least up to 10 successive generations on a cultural medium and in host plants.

Association of polymorphisms in bone morphogenetic protein receptor-1B gene exon-9 with litter size in Dorset, Mongolian, and Small Tail Han ewes

  • Jia, Jianlei;Chen, Qian;Gui, Linsheng;Jin, Jipeng;Li, Yongyuan;Ru, Qiaohong;Hou, Shengzhen
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.7
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    • pp.949-955
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    • 2019
  • Objective: The present study was to investigate the association of polymorphisms in exon-9 of the bone morphogenetic protein receptor-1B (BMPR-1B) gene (C864T) with litter size in 240 Dorset, 232 Mongolian, and 124 Small Tail Han ewes. Methods: Blood samples were collected from 596 ewes and genomic DNA was extracted using the phenol: chloroform extraction method. The 304-bp amplified polymerase chain reaction product was analyzed for polymorphism by single-strand conformation polymorphism method. The genotypic frequency and allele frequency of BMPR-1B gene exon-9 were computed after sequence alignment. The ${\chi}^2$ independence test was used to analyze the association of genotypic frequency and litter size traits with in each ewe breed, where the phenotype was directly treated as category. Results: The results indicated two different banding patterns AA and AB for this fragment, with the most frequent genotype and allele of AA and A. Calculated Chi-square test for BMPR-1B gene exon-9 was found to be more than that of p value at the 5% level of significance, indicating that the population under study was in Hardy-Weinberg equilibrium for all ewes. The ${\chi}^2$ independence test analyses indicated litter size differences between genotypes was not the same for each breed. The 304-bp nucleotide sequence was subjected to BLAST analysis, and the C864T mutation significantly affected litter size in singletons, twins and multiples. The heterozygosity in exon-9 of BMPR-1B gene could increase litter size for all the studied ewes. Conclusion: Consequently, it appears that the polymorphism BMPR-1B gene exon-9 detected in this study may have potential use in marker assisted selection for litter size in Dorset, Mongolian, and Small Tail Han ewes.

Analysis of virulence traits of Staphylococcus aureus isolated from bovine mastitis in semi-intensive and family dairy farms

  • Guzman-Rodriguez, Jaquelina J.;Leon-Galvan, Ma. Fabiola;Barboza-Corona, Jose E.;Valencia-Posadas, Mauricio;Loeza-Lara, Pedro D.;Sanchez-Ceja, Monica;Ochoa-Zarzosa, Alejandra;Lopez-Meza, Joel E.;Gutierrez-Chavez, Abner J.
    • Journal of Veterinary Science
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    • v.21 no.5
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    • pp.77.1-77.14
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    • 2020
  • Background: Staphylococcus aureus is one of the main microorganisms that causes bovine mastitis, and its well-known virulence characteristics and interactions with the environment are used to aid the design of more efficient therapies. Objectives: To determine whether the virulence traits, such as antibiotic resistance and biofilm-forming and internalization abilities, of S. aureus isolated from bovine mastitis are related to dairy production system types. Methods: The study was performed in the Mexican states of Guanajuato and Michoacan. Semi-intensive dairy farms (SIDFs) and family dairy farms (FDFs) (454 and 363 cows, respectively) were included. The 194 milk samples from mastitis affected quarters were collected and 92 strains of S. aureus were isolated and identified by biochemical and molecular tests. Antibiotic resistance, biofilm and internalization assays were performed on 30 randomly selected isolated strains to determine virulence traits, and these strains were equally allocated to the 2 dairy production systems. Results: All 30 selected strains displayed a high degree of resistance (50%-91.7%) to the antibiotics tested, but no significant difference was found between SIDF and FDF isolates. S. aureus strains from SIDFs had an average biofilm forming capacity of up to 36% (18.9%-53.1%), while S. aureus strains from FDFs registered an average of up to 53% (31.5%-77.8%) (p > 0.05). Internalization assays revealed a higher frequency of internalization capacity for strains isolated from FDFs (33.3%) than for those isolated from SIDFs (6.7%) (p > 0.05). fnbpA gen was detected in 46.6% of FDF strains and 33.3% of SIDF strains, and this difference was significant (p < 0.05). Conclusions: Our findings show that the virulence traits of S. aureus isolates analyzed in this study, depend significantly on several factors, such as phenotype, genotype, and environmental conditions, which are significantly related to dairy production system type and daily management practices.

Four Times of Relapse of Plasmodium vivax Malaria Despite Primaquine Treatment in a Patient with Impaired Cytochrome P450 2D6 Function

  • Choi, Sungim;Choi, Heun;Park, Seong Yeon;Kwak, Yee Gyung;Song, Je Eun;Shin, So Youn;Baek, Ji Hyeon;Shin, Hyun-IL;Oh, Hong Sang;Kim, Yong Chan;Yeom, Joon-Sup;Han, Jin-Hee;Kim, Min Jae
    • Parasites, Hosts and Diseases
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    • v.60 no.1
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    • pp.39-43
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    • 2022
  • Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

Association between a Genetic Variant of CACNA1C and the Risk of Schizophrenia and Bipolar I Disorder Across Diagnostic Boundaries (조현병과 제1형 양극성장애의 진단 경계를 넘어선 공통적 후보유전자로서의 CACNA1C에 대한 단일염기다형성 연합 연구)

  • Lee, Bora;Baek, Ji Hyun;Cho, Eun Young;Yang, So-Yung;Choi, Yoo Jin;Lee, Yu-Sang;Ha, Kyooseob;Hong, Kyung Sue
    • Korean Journal of Schizophrenia Research
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    • v.21 no.2
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    • pp.43-50
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    • 2018
  • Objectives : Genome-wide association studies (GWASs) and meta-analyses indicate that single-nucleotide polymorphisms (SNPs) in the a-1C subunit of the L-type voltage-dependent calcium channel (CACNA1C) gene increase the risk for schizophrenia and bipolar disorders (BDs). We investigated the association between the genetic variants on CACNA1C and schizophrenia and/or BDs in the Korean population. Methods : A total of 582 patients with schizophrenia, 336 patients with BDs consisting of 179 bipolar I disorder (BD-I) and 157 bipolar II disorder (BD-II), and 502 healthy controls were recruited. Based on previous results from other populations, three SNPs (rs10848635, rs1006737, and rs4765905) were selected and genotype-wise association was evaluated using logistic regression analysis under additive, dominant and recessive genetic models. Results : rs10848635 showed a significant association with schizophrenia (p=0.010), the combined schizophrenia and BD group (p=0.018), and the combined schizophrenia and BD-I group (p=0.011). The best fit model was dominant model for all of these phenotypes. The association remained significant after correction for multiple testing in schizophrenia and the combined schizophrenia and BD-I group. Conclusion : We identified a possible role of CACNA1C in the common susceptibility of schizophrenia and BD-I. However no association trend was observed for BD-II. Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.

Exonic SNP (rs7144, 3’-UTR) in CD46 Molecule and Complement Regulatory Protein (CD46) Gene Associated with Excess Syndrome to Categorize Korean Bronchial Asthma Patients (한국인 기관지 천식 허증(虛證), 실증(實證) 환자와 CD46 유전자 다형성과의 관계)

  • Lee, Mei;Baek, Hyun-jung;Park, Eui-keun;Kim, Kwan-il;Lee, Beom-joon;Kim, Su-kang;Chung, Joo-ho;Kim, Jin-ju;Kim, Mi-a;Jung, Hee-jae;Jung, Sung-ki
    • The Journal of Internal Korean Medicine
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    • v.36 no.4
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    • pp.547-561
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    • 2015
  • Objectives In this study, we divided Korean asthma patients into excess syndrome or deficiency syndrome groups according to clinical phenotype. Genetic analysis was conducted to investigate the association of exonic SNPs in the CD46 gene polymorphism with the clinical phenotype based on the differentiation syndrome of the bronchial asthma patients.Methods There were 95 healthy patients (control group) and 53 asthma patients. (The deficiency syndrome group included 24 and the excess syndrome group 29). We searched the exonic areas of the CD46 gene in the NCBI website SNPs with <0.01 minor allele frequency (MAF) and <0.01 heterozygosity. We finally selected two SNPs: rs138843816, Ser13Phe and rs7144, 3’-UTR. Hardy-Weinberg equilibrium was calculated using SNPStats.Results There were significant differences in the codominant 1 model and the dominant model between the healthy group and the asthma group. There were significant differences between deficiency syndrome group and the excess syndrome group in the genotype frequencies and in the codominant 1 model, the dominant model, and the log-additive model. The allele frequency of rs7144C showed a significant difference between the deficiency syndrome group and the excess syndrome group. Two-SNP haplotype analysis showed a significant difference in frequency in the deficiency syndrome group and in the excess syndrome group. There were significant differences between the healthy group and the excess syndrome group in the codominant 1 model, the dominant model, and the log-additive model. The frequency of the rs7144 C allele exhibited a significant difference in the demonstration. SNP haplotype analysis between the healthy group and the excess syndrome group showed a significant difference in the frequency of the CT haplotype and the CC haplotype.Conclusions The results indicate that two CD46 SNPs (rs138843816, Ser13Phe and rs7144, 3′–UTR) might be associated with the symptomatic excess syndrome in Korean asthma patients.

Molecular Cytogenetic Characterization of Supernumerary Marker Chromosomes by Chromosomal Microarray (염색체 마이크로어레이를 이용한 표지염색체의 분자세포유전학적 특성)

  • Bae, Mi-Hyun;Yoo, Han-Wook;Lee, Jin-Ok;Hong, Maria;Seo, Eul-Ju
    • Journal of Genetic Medicine
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    • v.8 no.2
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    • pp.119-124
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    • 2011
  • Purpose: Supernumerary marker chromosome (SMC) could be associated with various phenotypic abnormalities based on the chromosomal origin of SMCs. The present study aimed to determine the genomic contents of SMCs using chromosomal microarray and to analyze molecular cytogenetic characterizations and clinical phenotypes in patients with SMCs. Materials and Methods: Among patients with SMCs detected in routine chromosomal analysis, SMCs originating from chromosome 15 were excluded from the present study. CGH-based oligonucleotide chromosomal microarray was performed in 4 patients. Results: The chromosomal origins of SMCs were identified in 3 patients. Case 1 had a SMC of 16.1 Mb in 1q21.1-q23.3. Case 2 showed 21 Mb gain in 19p13.11-q13.12. Case 3 had a 4.5 Mb-sized SMC rearranged from 2 regions of 2.5 Mb in 22q11.1-q11.21 and 2.0 Mb in 22q11.22-q11.23. Conclusion: Case 1 presented a wide range of phenotypic abnormalities including the phenotype of 1q21.1 duplication syndrome. In case 2, Asperger-like symptoms are apparently related to 19p12-q13.11, hearing problems and strabismus to 19p13.11 and other features to 19q13.12. Compared with cat-eye syndrome type I and 22q11.2 microduplication syndrome, anal atresia in case 3 is likely related to 22q11.1-q11.21 while other features are related to 22q11.22-q11.23. Analyzing SMCs using high-resolution chromosomal microarray can help identify specific gene contents and to offer proper genetic counseling by determining genotype-phenotype correlations.