• Genomics & Informatics
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• 제14권1호
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• pp.34-40
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• 2016

Due to advances in omics technologies, numerous genome-wide studies on human samples have been published, and most of the omics data with the associated clinical information are available in public repositories, such as Gene Expression Omnibus and ArrayExpress. While analyzing several public datasets, we observed that errors in gender information occur quite often in public datasets. When we analyzed the gender description and the methylation patterns of gender-specific probes (glucose-6-phosphate dehydrogenase [G6PD], ephrin-B1 [EFNB1], and testis specific protein, Y-linked 2 [TSPY2]) in 5,611 samples produced using Infinium 450K HumanMethylation arrays, we found that 19 samples from 7 datasets were erroneously described. We also analyzed 1,819 samples produced using the Affymetrix U133Plus2 array using several gender-specific genes (X (inactive)-specific transcript [XIST], eukaryotic translation initiation factor 1A, Y-linked [EIF1AY], and DEAD [Asp-Glu-Ala-Asp] box polypeptide 3, Y-linked [DDDX3Y]) and found that 40 samples from 3 datasets were erroneously described. We suggest that the users of public datasets should not expect that the data are error-free and, whenever possible, that they should check the consistency of the data.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6211-6217
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• 2014

Previous genome-wide association studies (GWAS) have implicated several single nucleotide polymorphisms (SNPs) in the AT-rich interactive domain 5B (ARID5B) gene with childhood acute lymphoblastic leukemia (ALL). However, replicated studies reported some inconsistent results in different populations. Using meta-analysis, we here aimed to clarify the nature of the genetic risks contributed by the two polymorphisms (rs10994982, rs7089424) for developing childhood ALL. Through searches of PubMed, EMBASE, and manually searching relevant references, a total of 14 articles with 16 independent studies were included. Odds ratios (ORs) with 95% confidence intervals (95%CI) were calculated to assess the associations. Both SNPs rs10994982 and rs7089424 showed significant associations with childhood ALL risk in all genetic models after Bonferroni correction. Furthermore, subtype analyses of B-lineage ALL provided strong evidence that SNP rs10994982 is highly associated with the risk of developing B-hyperdiploid ALL. These results indicate that SNPs rs10994982 and rs7089424 are indeed significantly associated with increased risk of childhood ALL.

• BMB Reports
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• 제41권10호
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• pp.685-692
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• 2008

Colorectal cancer (CRC) is the third most common malignancy in the world. Because CRC develops slowly from removable precancerous lesions, detection of the disease at an early stage during regular health examinations can reduce both the incidence and mortality of the disease. Although sigmoidoscopy offers significant improvements in the detection rate of CRC, its diagnostic value is limited by its high costs and inconvenience. Therefore, there is a compelling need for the identification of noninvasive biomarkers that can enable earlier detection of CRC. Accordingly, many validation studies have been conducted to evaluate genetic, epigenetic or protein markers that can be detected in the stool or in serum. Currently, the fecal-occult blood test is the most widely used method of screening for CRC. However, advances in genomics and proteomics combined with developments in other relevant fields will lead to the discovery of novel non invasive biomarkers whose usefulness will be tested in larger validation studies. Here, non-invasive molecular biomarkers that are currently used in clinical settings and have the potential for use as CRC biomarkers are discussed.

• Journal of Genetic Medicine
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• 제13권1호
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• pp.51-54
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• 2016

Centronuclear myopathy (CNM) is a rare congenital myopathy that is pathologically characterized by the centrally located nuclei in most of the muscle fibers. On clinical examination, dynamin 2 (DNM2)-related CNM typically shows distal dominant muscle atrophy, ptosis, ophthalmoplegia, and contracture. The reported cases of CNM in Caucasian studies show a high prevalence rate of early-onset ptosis and ophthalmoplegia and correlated with the severity of the disease. However, Asian reports show a low prevalence and late-onset ocular symptoms in DNM2-related CNM patients. p.R465W is one of the most commonly found mutations in Western countries, and all the cases showed ocular symptoms. The proband and his daughter had no ocular symptoms despite harboring the same p.R465W mutation. This family makes us speculate that ocular symptoms in DNM2-related CNM are influenced by ethnic background. In addition, this is the first familial case of DNM2-related CNM in Korea.

• Journal of Genetic Medicine
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• 제13권1호
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• pp.46-50
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• 2016

Achondroplasia and hypochondroplasia are the two most common forms of short-limb dwarfism. They are autosomal dominant diseases that are characterized by a rhizomelic shortening of the limbs, large head with frontal bossing, hypoplasia of the mid-face, genu varum and trident hands. Mutations in the fibroblast growth factor receptor-3 (FGFR3) gene, which is located on chromosome 4p16.3, have been reported to cause achondroplasia and hypochondroplasia. More than 98% of achondroplasia cases are caused by the G380R mutation (c.1138G>A or c.1138G>C). In contrast, the N540K mutation (c.1620C>A) is detected in 60-65% of hypochondroplasia cases. Tests for common mutations are often unable to detect the mutation in patients with a clinical diagnosis of hypochondroplasia. In this study, we presented a case of familial hypochondroplasia with a rare mutation in FGFR3 identified by next generation sequencing.

• Journal of Genetic Medicine
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• 제15권1호
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• pp.34-37
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• 2018

A 1q21.1 microdeletion is an extremely rare chromosomal abnormality that results in phenotypic diversity and incomplete penetrance. Patients with a 1q21.1 microdeletion exhibit neurological-psychiatric problems, microcephaly, epilepsy, facial dysmorphism, cataract, and thrombocytopenia absent radius syndrome. We reported a neonate with confirmed intrauterine growth restriction (IUGR), micrognathia, glossoptosis, upper airway obstruction, facial dysmorphism, and eye abnormality at birth as well as developmental delay at the age of 1 year. These clinical manifestations, except for the IUGR and upper airway obstruction, in the neonate indicated a 1q21.1 microdeletion. Here, we report a rare case of a 1q21.1 microdeletion obtained via paternal inheritance in a newborn with upper airway obstruction caused by glossoptosis and tracheal stenosis.

• Journal of Genetic Medicine
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• 제15권1호
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• pp.38-42
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• 2018

WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome is a rare contiguous gene deletion syndrome caused by deleting genes including WT1 and PAX6 genes in 11p13 region, which is characterized by Wilms tumor, aniridia, genitourinary abnormalities, and intellectual disability. We report the clinical and cytogenetic characteristics of one Korean patient with WAGR syndrome. The patient shows bilateral sporadic aniridia and genital anomalies at 2 months of age. A heterozygous 14.5 Mb interstitial deletion of 11p14.3p12 region was detected by array comparative genomic hybridization. At 2 years and 10 months of age, Wilms tumor is found through regularly abdominal ultrasonography and treated by chemotherapy, radiation therapy and surgery.

• Genomics & Informatics
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• 제3권4호
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• pp.159-165
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• 2005

The Korean Twin Register (n=154,783 pairs) was reported in 2002 as the first nationwide twin study in Korea and the largest study in Asia. The Twin Register has the information of disease outcomes since 1990, and basic clinical and questionnaire data from biennial health examination provided by Korea National Health Service. The author attempted to calculate some of the genetic parameters of cancers in this population. Common cancers in Korea known to have familial aggregation (colon and breast) and cancers of which familial aggregation is unclear (stomach cancer) were examined for their familial recurrence risks. There were 699 stomach cancers, 438 breast and 491 colorectal cancers cases in the twin register between 1991 and 2003. Like-sex twins showed recurrence risks (${\lambda}_{LS}$) of 5.1 (95% CI 3.7-6.9) for stomach cancers, 15.5 (95% CI1 0.9-20.2) for female breast cancers, and 28.1 (95% CI 23.5-34.4) for colon cancers. Colorectal cancers of female like-sex twins show significantly higher familial recurrence risk 40.7 (95% CI 34.6-47.4), suggesting higher genetic contribution in women than in men. The results show increased familial risks compared with previous studies from the same register and are largely compatible with other studies. The data of the Twin Register could be used for estimating population level genetic parameters, as well as base of the various studies.

• Genomics & Informatics
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• 제12권4호
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• pp.276-282
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• 2014

The disease tuberculosis, caused by Mycobacterium tuberculosis (MTB), remains a major cause of morbidity and mortality in developing countries. The evolution of drug-resistant tuberculosis causes a foremost threat to global health. Most drug-resistant MTB clinical strains are showing resistance to isoniazid and rifampicin (RIF), the frontline anti-tuberculosis drugs. Mutation in rpoB, the beta subunit of DNA-directed RNA polymerase of MTB, is reported to be a major cause of RIF resistance. Amongst mutations in the well-defined 81-base-pair central region of the rpoB gene, mutation at codon 450 (S450L) and 445 (H445Y) is mainly associated with RIF resistance. In this study, we modeled two resistant mutants of rpoB (S450L and H445Y) using Modeller9v10 and performed a docking analysis with RIF using AutoDock4.2 and compared the docking results of these mutants with the wild-type rpoB. The docking results revealed that RIF more effectively inhibited the wild-type rpoB with low binding energy than rpoB mutants. The rpoB mutants interacted with RIF with positive binding energy, revealing the incapableness of RIF inhibition and thus showing resistance. Subsequently, this was verified by molecular dynamics simulations. This in silico evidence may help us understand RIF resistance in rpoB mutant strains.

• Genomics & Informatics
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• 제3권3호
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• pp.68-73
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• 2005

Pharmacogenomics research requires an intelligent integration of large-scale genomic and clinical data with public and private knowledge resources. We developed a web-based knowledge base for KPRN (Korea Pharmacogenomics Research Network, http://kprn.snubi. org/). Four major types of information is integrated; genetic variation, drug information, disease information, and literature annotation. Eighteen Korean pharmacogenomics research groups in collaboration have submitted 859 genotype data sets for 91 disease-related genes. Integrative analysis and visualization of the large collection of data supported by integrated biomedical path­ways and ontology resources are provided with a user-friendly interface and visualization engine empowered by Generic Genome Browser.