• 생물정신의학
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• 제23권4호
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• pp.148-156
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• 2016

Objectives According to previous studies, the cannabinoid receptor 1 (CNR1) gene could be an important candidate gene for schizophrenia. Some studies have linked the (AAT)n trinucleotide repeat polymorphism in CNR1 gene with the risk of schizophrenia. Meanwhile, smooth pursuit eye movement (SPEM) has been regarded as one of the most consistent endophenotypes of schizophrenia. In this study, we investigated the association between the (AAT)n trinucleotide repeats in CNR1 gene and SPEM abnormality in Korean patients with schizophrenia. Methods We measured SPEM function in 167 Korean patients with schizophrenia (84 male, 83 female) and they were divided according to SPEM function into two groups, good and poor SPEM function groups. We also investigated allele frequencies of (AAT)n repeat polymorphisms on CNR1 gene in each group. A logistic regression analysis was performed to find the association between SPEM abnormality and the number of (AAT)n trinucleotide repeats. Results The natural logarithm value of signal/noise ratio (Ln S/N ratio) of the good SPEM function group was $4.34{\pm}0.29$ and that of the poor SPEM function group was $3.21{\pm}0.70$. In total, 7 types of trinucleotide repeats were identified, each containing 7, 10, 11, 12, 13, 14, and 15 repeats, respectively. In the patients with $(AAT)7$ allele, the distributions of the good and poor SPEM function groups were 18 (11.1%) and 19 (11.0%) respectively. In the patients with $(AAT)_{10}$ allele, $(AAT)_{11}$ allele, $(AAT)_{12}$ allele, $(AAT)_{13}$ allele, $(AAT)_{14}$ allele and $(AAT)_{15}$ allele, the distributions of good and poor SPEM function groups were 13 (8.0%) and 12 (7.0%), 4 (2.5%) and 6 (3.5%), 31 (19.8%) and 35 (20.3%), 51 (31.5%) and 51 (29.7%), 36 (22.2%) and 45 (26.2%), 9 (5.6%) and 4 (2.3%) respectively. As the number of (AAT) n repeat increased, there was no aggravation of abnormality of SPEM function. Conclusions There was no significant aggravation of SPEM abnormality along with the increase of number of (AAT)n trinucleotide repeats in the CNR1 gene in Korean patients with schizophrenia.

• Journal of Genetic Medicine
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• 제12권1호
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• pp.38-43
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• 2015

Purpose: Spinocerebellar ataxias (SCAs) are progressive neurodegenerative disorders with diverse modes of inheritance. There are several subtypes of SCAs. SCA 8, SCA 12, and SCA 17 are the less common forms of SCAs with limited information available on their epidemiological profiles in Korea. The purpose of this study was to investigate the prevalence of SCA8, SCA12, and SCA17 in Korea. Materials and Methods: Ninety-six unrelated Korean patients were enrolled and showed normal trinucleotide repeats through polymerase-chain reaction (PCR) for the genes ATXN1, ATXN2, ATXN3, CACNA1A, and ATXN7, which correspond to SCA1, SCA2, SCA3, SCA6, and SCA7, respectively. PCR products from patients were further analyzed by capillary electrophoresis using fluorescence labeled primers for the genes ATXN8OS, PPP2R2B, and TBP, which correspond to SCA8, SCA12, and SCA17. Results: Three patients had 104, 97, and 75 abnormal expanded repeats in the ATXN8OS gene, the causative gene for SCA8. None of the patients exhibited abnormal repeats in SCA12 and SCA17. Normal trinucleotide repeat ranges of the cohort in this study were estimated to be 17-34 copies (average, $24{\pm}4copies$) for SCA8, 7-18 copies (average, $13{\pm}3copies$) for SCA12, and 26-43 copies (average, $35{\pm}2copies$) for SCA17. Conclusion: This study demonstrated that SCA8, SCA12, and SCA17 are rare in Korean patients with SCA, and further genetic studies are warranted to enhance the mutation detection rate in the Korean SCA population.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 춘계학술발표회
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• pp.38-38
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• 2018

The genus Carduus (Asteraceae), containing ca. 90 species, is mainly distributed in Eurasia and Africa. Carduus species are one of the most hazardous invasive species, which causes serious environmental threats and biodiversity damages in North America. Thus, the member of Carduus are targeted for classical biological control in this region. Here, we provide the complete cp genome of Carduus crispus using next-generation sequencing technology. The size of cp genomes of C. crispus is 152,342 bp. It shows a typical quadripartite structure, consisting of the large single copy (LSC; 83,254 bp), small single copy (SSC; 18,706 bp), separated by a pair of inverted repeats (IRs; 25,191 bp). It contains 115 unique genes of which 21 genes duplicated in the IR regions. The cpSSR regions of Carduus species were searched through the complete chloroplast genome sequence using a tandem repeat search tool in Geneious with the parameters set to ${\geq}7$ mononucleotide repeats, ${\geq}4$ di- and trinucleotide repeats, and ${\geq}3$ tetra-, penta-, and hexanucleotide repeats. A total of 22 repeat motifs were identified, which may be useful for molecular identification of Korean Carduus species (C. cripus), and providing a guideline for its conservation.

• 생물정신의학
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• 제21권3호
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• pp.99-106
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• 2014

Objectives Previous studies suggest that the cannabinoid receptor 1 (CNR1) gene could be an important candidate gene for schizophrenia. According to linkage studies, this gene is located on chromosome 6q14-q15, which is known to harbor the schizophrenia susceptibility locus (locus 5, SCZ5, OMIM 803175). The pharmacological agent delta-9-tetrahydrocannabinol (${\Delta}$-9-THC) seems to elicit the symptoms of schizophrenia. The association between CNR1 polymorphisms and schizophrenia is actively being investigated, and some studies have linked the AAT-trinucleotide repeats in CNR1 to the onset of schizophrenia. In this study, we have investigated the association between the AAT-trinucleotide repeats in CNR1 and schizophrenia by studying schizophrenia patients and healthy individuals from Korea. Methods DNA was extracted from the blood samples of 394 control subjects and 337 patients diagnosed with schizophrenia (as per the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria). After polymerase chain reaction amplification, a logistic regression analysis, with age and gender as the covariates, was performed to study the variations in the AAT-repeat polymorphisms between the two groups. Results In total, 8 types of trinucleotide repeats were identified, each containing 7, 8, 10, 11, 12, 13, 14, and 15 repeats, respectively. $(AAT)_{13}$ allele was most frequently observed, with a frequency of 33.6% and 31.6% in the patient and control groups, respectively. The frequency of the other repeat alleles in the patient group (in the decreasing order) was as follows : $(AAT)_{13}$ 33.6%, $(AAT)_{14}$ 21.6%, $(AAT)_{12}$ 18.5%, and $(AAT)_{7}$ 11.1%. The frequency of the repeat alleles in the control group (in the decreasing order) was as follows : $(AAT)_{13}$ 31.6%, $(AAT)_{14}$ 24.5%, $(AAT)_{12}$ 17.2%, and $(AAT)_{7}$ 11.6%. However, there were no significant differences in the AAT-repeat polymorphisms of the CNR1 gene between the patient group and the control group. Conclusions Although our study revealed no significant association of the AAT-repeat polymorphism of the CNR1 gene with schizophrenia, it will serve as a good reference for future studies designed to examine the cannabinoid hypothesis of schizophrenia.

• Clinical and Experimental Reproductive Medicine
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• 제34권3호
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• pp.179-188
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• 2007

목 적: 본 연구에서는 삼핵산 반복서열 확장에 의해 발병하는 헌팅톤병, 척수소뇌성 운동실조증과 X-염색체 취약 증후군 등에 대한 착상전 유전진단을 시행하기 위한 전임상 검사에서 진단 방법을 최적화하는 과정을 통해 얻은 결과들에 대해 기술하고자 한다. 연구방법: 단일 림프구를 이용한 임상전 검사에서는 서로 다른 allele를 갖고 있는 환자의 단일 세포를 사용하였으며, 헌팅톤병과 척수소뇌성 운동실조증에서는 fluorescent semi-nested PCR 시행 후 fragment analysis를 수행하였다. X-염색체 취약 증후군의 경우 multiple displacement amplification (MDA) 방법을 이용한 whole genome amplification에서 얻어진 MDA 산물로 fluorescent PCR을 시도하였다. 결 과: 헌팅톤병의 경우 단일 림프구 시료 모두에서 CAG repeats 증폭에 성공하여 100.0%의 증폭성공률과 14.0% allele drop-out (ADO) rate를, 척수소뇌성 운동실조증의 경우 94.7%의 증폭성공률과 5.6%의 ADO rate을 나타내었다. X-염색체 취약 증후군의 경우 fluorescent semi-nested PCR 방법만으로는 단일 림프구 시료에서 CGG repeats이 증폭되지 않았지만, MDA 산물을 이용한 fluorescent PCR 결과 84.2%의 증폭성공률과 31.3%의 ADO rate을 얻을 수 있었다. 결 론: 본 연구를 통해 헌팅톤병과 척수소뇌성 운동실조증의 착상전 유전진단에는 fluorescent semi-nested PCR 방법의 적용이 가능함을 확인하였으며, X-염색체 취약 증후군의 경우에는 MDA를 이용한 fluorescent PCR 방법을 사용해야 함을 알 수 있었다. 유전자의 변이에 대한 분석이 쉽지 않은 단일 유전자 이상에 대한 착상전 유전진단의 경우 다양한 유전자 분석 방법을 이용한 단일 세포에서의 진단 방법의 최적화 연구가 필수적으로 선행되어야 할 것으로 사료된다.

• Journal of Genetic Medicine
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• 제1권1호
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• pp.23-26
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• 1997

Myotonic dystrophy (DM) is caused by the expansion of CTG trinucleotide repeat near the 3' end of the gene encoding for a member of protein kinase gene family (DMPK). The normal range of the CTG repeat was determined in 178 normal individuals (141 unrelated individuals and 37 of 9 families) by polymerase chain reaction (PCR), polyacrylamide gel electrophoresis and silver staining method. And the expansion of the CTG repeats in a DM family was analyzed with Southern analysis. In normal population, the range of CTG repeat is between 5 and 34 and 19 different alleles were observed in that range, and $(CTG)_{11-14}$ alleles were predominant. 4 members of an affected family showed the 0.5-2.0 kb size expansion of CTG repeats. In this study we could predict the incidence of DM in Korea as 1 in 20,000 and we could establish the diagnostic procedure for myotonic dystrophy.

• Journal of Genetic Medicine
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• 제5권1호
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• pp.41-46
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• 2008

목 적 : 취약 X 증후군(fragile X syndrome)은 FMR1 유전자의 5' 비해독부위에 있는 CGG 3염기 반복의 확장에 의해 발생되는 유전성 질환이다. 방 법 : 본 연구에서는 임상 소견과 핵형분석에서 취약 X 증후군으로 진단 받은 여아 환자와 그 부모를 대상으로 Abbott Molecular Fragile X PCR Kit를 이용하여 CGG 3염기 영역을 PCR로 증폭하여 normal, premutation, full mutation의 CGG 반복의 유형을 확인하였으며, premutation과 normal allele의 경우에는 정확한 CGG 반복수를 분석하였다. 결 과 : 환자는 30회와 >200회의 CGG 3염기가 반복된 FMR1 대립유전자를 갖고 있는 것으로 확인되어 취약 X 증후군으로 진단되었다. 또한 환자의 어머니에서 30과 98회의 반복 allele을 확인함으로써, 이 환자의 full mutation allele은 모계의 premutation allele로부터 유래한 것임을 알 수 있었다. 결 론 : Abbott Molecular Fragile X PCR Kit를 사용한 진단방법은, 취약 X 증후군환자의 경우에서 통상적으로 시행되고 있는 PCR, MS-PCR, Southern blotting을 병행하는 방법에 비해 신속하고 정확한 분자유전학적 진단이 가능한 유용한 방법이라 생각된다.

• Journal of Genetic Medicine
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• 제11권2호
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• pp.69-73
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• 2014

Purpose: Spinocerebellar ataxia (SCA) is a genetically heterogeneous disease for which more than 30 subtypes have been identified. However, 5 subtypes, SCA1, SCA2, SCA3, SCA6, and SCA7, account for more than 60% of cases. In this study, we report the distribution of these 5 subtypes in Korean patients. Materials and Methods: Six hundred and thirty-eight unrelated patients with a presumptive diagnosis of SCA were included in this study. Trinucleotide (CAG) repeat number (TNR) repeat number was determined using fluorescently labeled primers and fragment analysis. Results: A total of 128 unrelated patients (20.1% of all individuals tested) tested positive for SCA subtypes, including SCA1 (5 patients, 3.9% of those testing positive), SCA2 (38 patients, 29.7%), SCA3 (30 patients, 23.4%), SCA6 (39 patients, 30.5%), and SCA7 (16 patients, 12.5%). The mean copy number of pathogenic TNR alleles was $45{\pm}8.5$ for SCA1, $42{\pm}3.1$ for SCA2, $72{\pm}5.4$ for SCA3, $23{\pm}1.5$ for SCA6, and $50{\pm}11.4$ for SCA7. TNR copy number was inversely correlated with onset age in SCA2, SCA6, and SCA7. Conclusion: SCA2, SCA3, and SCA6 are common SCA subtypes in Korean patients and could be screened as a first-line test. Expanded pathogenic allele size was associated with early onset age.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제11권1호
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• pp.3-15
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• 2000

연구목적：자폐장애의 원인을 유전학적으로 규명하려는 연구가 시도되고 있으며, 그 중 fragile X 증후군과의 연관성에 대한 연구가 활발히 진행되고 있다. Fragile X 염색체(Xq27.3)는 세포유전학적 방법으로 증명할 수 있으나 검사에 많은 제약과 단점이 있으므로, 본 연구에서는 보다 신뢰성이 높은 분자생물학적 방법으로 FMR-1 유전자내 CGG 삼염기 반복부위를 분석하여 자폐장애와 fragile X 증후군의 연관성을 규명하고자 하였다. 방 법：자폐장애 환아(99명)와 정상대조군(8명)을 대상으로 FMR-1 유전자의 CGG 반복배열 부위를 sense와 antisense primer를 이용하여 PCR법으로 분석하였으며, 동시에 세포유전학적 검사도 시행하였다. PCR 분석에서 CGG 반복수가 50 이상인 경우에 대해서는 StB12.3 혹은 Pfxa3 probe를 이용한 Southern blot hybridization으로 확인하였다. 결 과：FMR-1 유전자의 CGG 반복배열에 대한 PCR 분석 결과 CGG 삼염기의 반복배열의 수는 자폐장애 환자군과 정상대조군 사이에 통계적으로 유의한 차이가 없었다(p=0.207). 자폐장애 환자에서 CGG반복수가 50회 이상인 조기변이(premutation) 환자가 2명 있었으나 Southern blot hybridization 결과 완전변이(full mutation)로 판정할 수 있는 경우는 없었다. 세포유전학적 검사에서 환자군 모두에서 정상 핵형을 나타내었으며 fragile X 염색체는 확인되지 않았다. 결 론：이상의 결과에서 자폐장애 환자가 FMR-1 유전자의 CGG 삼염기 반복부위 이상, 즉 fragile X 염색체 이상을 동반하지 않았음을 증명할 수 있었다. 이는 fragile X 증후군을 자폐장애의 직접적인 원인이라고 보기에는 어려움이 있음을 시사한다.

• Molecules and Cells
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• 제23권3호
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• pp.349-356
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• 2007

Simple Sequence Repeats (SSRs) represent short tandem duplications found within all eukaryotic organisms. To examine the distribution of SSRs in the genome of Brassica rapa ssp. pekinensis, SSRs from different genomic regions representing 17.7 Mb of genomic sequence were surveyed. SSRs appear more abundant in non-coding regions (86.6%) than in coding regions (13.4%). Comparison of SSR densities in different genomic regions demonstrated that SSR density was greatest within the 5'-flanking regions of the predicted genes. The proportion of different repeat motifs varied between genomic regions, with trinucleotide SSRs more prevalent in predicted coding regions, reflecting the codon structure in these regions. SSRs were also preferentially associated with gene-rich regions, with peri-centromeric heterochromatin SSRs mostly associated with retrotransposons. These results indicate that the distribution of SSRs in the genome is non-random. Comparison of SSR abundance between B. rapa and the closely related species Arabidopsis thaliana suggests a greater abundance of SSRs in B. rapa, which may be due to the proposed genome triplication. Our results provide a comprehensive view of SSR genomic distribution and evolution in Brassica for comparison with the sequenced genomes of A. thaliana and Oryza sativa.