• Journal of Preventive Medicine and Public Health
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• 제35권2호
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• pp.83-91
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• 2002

Bioinformatics is a rapidly emerging field of biomedical research. A flood of large-scale genomic and postgenomic data means that many of the challenges in biomedical research are now challenges in computational sciences. Clinical informatics has long developed methodologies to improve biomedical research and clinical care by integrating experimental and clinical information systems. The informatics revolutions both in bioinformatics and clinical informatics will eventually change the current practice of medicine, including diagnostics, therapeutics, and prognostics. Postgenome informatics, powered by high throughput technologies and genomic-scale databases, is likely to transform our biomedical understanding forever much the same way that biochemistry did a generation ago. The paper describes how these technologies will impact biomedical research and clinical care, emphasizing recent advances in biochip-based functional genomics and proteomics. Basic data preprocessing with normalization, primary pattern analysis, and machine learning algorithms will be presented. Use of integrated biochip informatics technologies, text mining of factual and literature databases, and integrated management of biomolecular databases will be discussed. Each step will be given with real examples in the context of clinical relevance. Issues of linking molecular genotype and clinical phenotype information will be discussed.

• 생물정신의학
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• 제28권1호
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• pp.1-6
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• 2021

Pharmacogenetics is opening a new era of precision medicine in psychiatry. Drug-metabolizing enzymes are characterized by genetic polymorphisms, which render a large portion of variability in individual drug metabolism. Dose adjustment based on pharmacogenetics knowledge is a first step to translate pharmacogenetics into clinical practice. However, diverse factors including cost-effectiveness should be addressed to provide clinical recommendation. To address current challenges in pharmacogenetics testing in psychiatry, this review provides an update regarding genotyping (SNP analysis, array, and next-generation sequencing), genotype-phenotype correlations, and cost-effectiveness. The current updates on pharmacogenetics in psychiatry will provide guidance for both clinician and researchers to have a consensus in harmonizing efforts to advance the pharmacogenetics field in a part of precision medicine in psychiatry.

• Genomics & Informatics
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• 제20권4호
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• pp.49.1-49.7
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• 2022

Many packages for a meta-analysis of genome-wide association studies (GWAS) have been developed to discover genetic variants. Although variations across studies must be considered, there are not many currently-accessible packages that estimate between-study heterogeneity. Thus, we propose a python based application called Beta-Meta which can easily process a meta-analysis by automatically selecting between a fixed effects and a random effects model based on heterogeneity. Beta-Meta implements flexible input data manipulation to allow multiple meta-analyses of different genotype-phenotype associations in a single process. It provides a step-by-step meta-analysis of GWAS for each association in the following order: heterogeneity test, two different calculations of an effect size and a p-value based on heterogeneity, and the Benjamini-Hochberg p-value adjustment. These methods enable users to validate the results of individual studies with greater statistical power and better estimation precision. We elaborate on these and illustrate them with examples from several studies of infertility-related disorders.

• Clinical and Experimental Pediatrics
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• 제51권3호
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• pp.315-322
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• 2008

목 적 : PWS의 두 가지 대표적 유전형인 미세결실형과 mUPD (15)형에서, 유전형에 따른 표현형의 차이와 성장 호르몬 투여 효과의 차이를 비교해 보고자 하였다. 방 법 : 1990년 1월부터 2007년 1월까지 서울아산병원에서 15번 염색체의 미세 결실에 대한 FISH 검사 및 메틸화-특이 PCR 검사를 통해 PWS로 확진된 53명의 환자를 대상으로 하였다. 출생시 부모의 연령, 출생 체중, PWS의 주요 표현형인 신생아 시기의 저긴장증, 수유 문제, 남아의 경우 잠복 고환, 발달 지연 및 정신 지체, 저신장, 저색소증, 사시, 척추측만증 등의 유무, 성장 호르몬 치료 전과 치료 후의 신장, 체중, 체질량 지수의 변화를 조사하였고 미세결실형 군과 mUPD(15)형 군으로 나누어 유전형에 따른 차이를 분석하였다. 결 과 : 유전학적 검사상 53명의 대상 환아 모두 미세결실형 또는 mUPD(15)형으로 진단되었으며, 미세결실형은 39명, mUPD (15)형은 14명이었다. 평균 진단 연령은 $4.51{\pm}5.19$세였다. 출생 당시 부모의 연령은 mUPD(15)형 군에서 유의하게 높았으며(P=0.0001), 저색소증(P=0.0001)과 신생아기의 수유 부전(P=0.049)은 미세결실형에서 유의하게 많았으나, 그 외의 조사된 표현형에서는 두 군 간에 통계적으로 의미 있는 차이는 없었다. 성장 호르몬은 20명의 환아[미세결실형 14명, mUPD(15)형 6명]에게 평균 $27.9{\pm}11.9$개월 동안 투여되었다. 두 유전형 간에 성장 호르몬 치료 전 및 치료 후의 신장 SDS, 체중 SDS, 체질량지수, IGF-1, IGFBP3, 신장 증가 속도, 체중 증가 속도의 값에는 의미 있는 차이가 없었다. 결 론 : PWS의 주요한 두 유전형의 비교에서, 부모의 연령은 mUPD(15)형에서 의미 있게 높았으며 신생아기 수유 부전과 저색소증은 결실형에서 의미 있게 많았다. 성장 호르몬의 치료 효과에서는 두 유전형 간에 의미 있는 반응의 차이는 없었다. 향후 두 유전자형과 다른 표현형들(예를 들면 행동, 발달, 지능 등) 과의 연관성에 관한 전향적 연구가 더 필요할 것으로 생각된다.

• Molecules and Cells
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• 제38권9호
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• pp.781-788
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• 2015

Mutations of MYO15A are generally known to cause severe to profound hearing loss throughout all frequencies. Here, we found two novel MYO15A mutations, c.3871C>T (p.L1291F) and c.5835T>G (p.Y1945X) in an affected individual carrying congenital profound sensorineural hearing loss (SNHL) through targeted resequencing of 134 known deafness genes. The variant, p.L1291F and p.Y1945X, resided in the myosin motor and IQ2 domains, respectively. The p.L1291F variant was predicted to affect the structure of the actin-binding site from three-dimensional protein modeling, thereby interfering with the correct interaction between actin and myosin. From the literature analysis, mutations in the N-terminal domain were more frequently associated with residual hearing at low frequencies than mutations in the other regions of this gene. Therefore we suggest a hypothetical genotype-phenotype correlation whereby MYO15A mutations that affect domains other than the N-terminal domain, lead to profound SNHL throughout all frequencies and mutations that affect the N-terminal domain, result in residual hearing at low frequencies. This genotype-phenotype correlation suggests that preservation of residual hearing during auditory rehabilitation like cochlear implantation should be intended for those who carry mutations in the N-terminal domain and that individuals with mutations elsewhere in MYO15A require early cochlear implantation to timely initiate speech development.

• Asian-Australasian Journal of Animal Sciences
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• 제20권1호
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• pp.41-44
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• 2007

The callipyge mutation in sheep is a polar overdominant mutation that results in post-natal muscle hypertrophy in the loin and hindquarters of paternal heterozygotes (+/CLPG). Sheep that are homozygous for the callipyge allele (CLPG/CLPG) do not express the muscle hypertrophy phenotype, but serve as carriers for the mutation. Callipyge sheep are characterized by improved feed efficiencies and leaner carcasses. Leptin is a protein hormone secreted from adipose tissue and has been found to affect appetite and serve as an indicator of body fat mass. To date, very little knowledge is available as to the effect of the callipyge mutation on circulating leptin levels. Due to the interaction of leptin with feed intake and energy availability, and the fact that the majority of fetal growth occurs in late gestation, it is important to understand if the callipyge mutation interacts with leptin production in late gestational ewes. Therefore, our objective was to characterize serum concentrations of leptin in late gestational callipyge ewes vs. non-callipyge ewes. We evaluated genetically verified callipyge (n=6), homozygous (n=8) and normal (n=8) ewes weekly during the last eight wks of gestation through one wk post-partum. Weights were taken and body condition scores were assigned by trained personnel weekly. Blood was collected via jugular venipuncture on each sampling date and subjected to an ovine-specific leptin RIA. Genotype influences on peripheral concentrations of leptin were found to be highly significant (p=0.0005). Total leptin means for +/CLPG were 5.41${\pm}$0.40 ng/ml, CLPG/CLPG 8.11${\pm}$0.70 ng/ml, and +/+ 9.13${\pm}$0.93 ng/ml. Sampling date was also significant (p=0.0098) with all ewes showing a decrease in leptin levels throughout gestation and parturition. Using repeated measures, we were able to detect lower levels of plasma leptin in callipyge ewes, which may be indicative of their lower overall body fat content. These results indicate that the callipyge phenotype decreases the levels of adipose tissue and leptin production in gestating ewes.

• Clinical and Experimental Pediatrics
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• 제53권8호
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• pp.809-813
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• 2010

Bartter syndrome (BS) is an autosomal recessively inherited rare renal tubular disorder characterized by hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism with normal to low blood pressure due to a renal loss of sodium. Genetically, BS is classified into 5 subtypes according to the underlying genetic defects, and BS is clinically categorized into antenatal BS and classical BS according to onset age. BS type I is caused by loss-of-function mutations in the $SLC12A1$ gene and usually manifests as antenatal BS. This report concerns a male patient with compound heterozygous missense mutations on $SLC12A1$ (p.C436Y and p.L560P) and atypical clinical and laboratory features. The patient had low urinary sodium and chloride levels without definite metabolic alkalosis until the age of 32 months, which led to confusion between BS and nephrogenic diabetes insipidus (NDI). In addition, the clinical onset of the patient was far beyond the neonatal period. Genetic study eventually led to the diagnosis of BS type I. The low urinary sodium and chloride concentrations may be caused by secondary NDI, and the later onset may suggest the existence of a genotype-phenotype correlation. In summary, BS type I may have phenotype variability including low urine sodium and chloride levels and later onset. A definitive diagnosis can be confirmed by genetic testing.

• Journal of Genetic Medicine
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• 제19권2호
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• pp.85-93
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• 2022

Purpose: Cornelia de Lange syndrome (CdLS) is a rare genetically heterogeneous disorder caused by genetic variants of the cohesin complex. However, the diverse genetic etiologies and their phenotypic correlations in Korean patients with CdLS are still largely unknown. Hence, this study aimed to clarify the clinical characteristics and genetic background of Korean patients with CdLS. Materials and Methods: The medical records of 15 unrelated patients (3 males and 12 females) genetically confirmed to have CdLS were retrospectively reviewed. All individuals were diagnosed with CdLS using target gene analysis, whole-exome sequencing, and/or chromosomal microarray analysis. The clinical score (CS) was calculated to assess disease severity. Results: The median age at diagnosis was 1.7 (range, 0.0-11.8) years, and median follow-up duration was 3.8 (range, 0.4-11.7) years. Eight (53.3%) patients showed classic phenotypes of CdLS, two (13.3%) showed non-classic phenotypes, and five (33.3%) had other phenotypes sharing limited signs of CdLS. Fifteen causative variants were identified: NIPBL in five (33.3%, including 3 males), SMC1A in three (20.0%), SMC3 in three (20.0%), and HDAC8 in four (26.7%) patients. The CS was significantly higher in the NIPBL group than in the non-NIPBL group (14.2±1.3 vs. 8.7±2.9, P<0.001). Conclusion: We identified the clinical and genetic heterogeneity of CdLS in Korean patients. Patients with variants of NIPBL had a more distinctive phenotype than those carrying variants of other cohesin complex genes (SMC1A, SMC3, and HDAC8). However, further studies are warranted to understand the pathogenesis of CdLS as a cohesinopathy and its genotype-phenotype correlations.

• 생물정신의학
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• 제10권2호
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• pp.159-167
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• 2003

Objective:Under the hypothesis that 5-HTTLPR polymorphism plays some role in the susceptibility or vulnerability of some subgroup of alcohol dependence, associations of 5-HTTLPR polymorphism with alcohol dependence were examined. Method:This association analysis included 109 Korean alcohol dependent and 113 Korean control subjects. DNA of all subjects were genotyped for the biallelic functional polymorphism in the 5-HTTLPR. Considering the likelihood of heterogeneity in the alcohol dependence phenotype, alcohol dependent subjects were subgrouped by onset age, family history of alcohol dependence and severity of withdrawal symptoms. Results:There were no significant differences in the frequencies of either the 5-HTTLPR genotype or the short vs. long allele in alcohol dependent and control subjects. The frequency of the S allele and S-carrier (LS or SS genotype) was significantly increased in the early onset alcohol dependent subjects and the familial alcohol dependent subjects compared with that in the control subjects. Conclusion:The results suggest that the 5-HTT 'S' promoter polymorphism is associated with an increased susceptibility or vulnerability to develop early onset alcohol dependence and familial alcohol dependence, which characterize Cloninger's type 2 alcohol dependence.

• 대한유전성대사질환학회지
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• 제4권1호
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• pp.5-12
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• 2004

Purpose Phenylketonuria is an inborn error of metabolism, which is inherited as an autosomal recessive trait. PKU is resulting from deficiency of phenylalanine hydroxylase. PAH gene spans about 90 kb on chromosome 12q and comprises 13 exons. In order to define the genetic basis of PKU and the frequencies and distribution of PAH mutations in the Korean population, we analyzed PAH gene in independent 80 patients with PKU. Methods All 13 exons including exon-intron boundaries and 2 kb of 5' upstream region of the PAH gene were analyzed by PCR-direct sequencing methods. Results PAH gene analysis revealed 39 different mutations including 10 novel mutations. The novel mutations consisted of 9 missense mutations (P69S, G103S, N207D, T278S, P281A, L293M, G332V, S391I and A447P) and a novel splice site variant (IVS10-3C>G). R243Q, IVS4-1G>A, and E6-96A>G were the most relevant mutations and they accounted in the whole for 38% of the mutant alleles identified in this study. We also observed that. $BH_4$ responsibility was. associated with genotype of R241C, R53H and R408Q. Conc1ustion Our present study with 80 participants extends the previous results to more comprehensive understanding of PAH allele distribution and frequency in Koreans. Although Korean mutation profile of PAH is similar to those of the nearest oriental populations (Japanese, Chinese, and Taiwanese), several different characteristic features are revealed. The characterization of the genotype-phenotype relationship was also performed. Our data would be very useful information for diagnosis, genetic counseling and planning of dietary and therapeutic strategies in Korean PAH patients.