• Journal of the Korean Data and Information Science Society
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• v.23 no.1
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• pp.1-11
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• 2012

When the microarray experiment developed, main interest was limited to detect differentially expressed genes associated with a phenotype of interest. However, as human diseases are thought to occur through the interactions of multiple genes within a same functional category, the unit of analysis of the microarray experiment expanded to the set of genes. For the phenotype of censored survival time, Gene Set Enrichment Analysis(GSEA), Global test and Wald type test are widely used. In this paper, we modified the Wald type test by adopting normal score transformation of gene expression values and developed a parametric test which requires much less computation than others. The proposed method is compared with other methods using a real data set of ovarian cancer and a simulation data set.

• Biomolecules & Therapeutics
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• v.22 no.5
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• pp.371-383
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• 2014

The nematode Caenorhabditis elegans (C. elegans) offers a unique opportunity for biological and basic medical researches due to its genetic tractability and well-defined developmental lineage. It also provides an exceptional model for genetic, molecular, and cellular analysis of human disease-related genes. Recently, C. elegans has been used as an ideal model for the identification and functional analysis of drugs (or small-molecules) in vivo. In this review, we describe conserved oncogenic signaling pathways (Wnt, Notch, and Ras) and their potential roles in the development of cancer stem cells. During C. elegans germline development, these signaling pathways regulate multiple cellular processes such as germline stem cell niche specification, germline stem cell maintenance, and germ cell fate specification. Therefore, the aberrant regulations of these signaling pathways can cause either loss of germline stem cells or overproliferation of a specific cell type, resulting in sterility. This sterility phenotype allows us to identify drugs that can modulate the oncogenic signaling pathways directly or indirectly through a high-throughput screening. Current in vivo or in vitro screening methods are largely focused on the specific core signaling components. However, this phenotype-based screening will identify drugs that possibly target upstream or downstream of core signaling pathways as well as exclude toxic effects. Although phenotype-based drug screening is ideal, the identification of drug targets is a major challenge. We here introduce a new technique, called Drug Affinity Responsive Target Stability (DARTS). This innovative method is able to identify the target of the identified drug. Importantly, signaling pathways and their regulators in C. elegans are highly conserved in most vertebrates, including humans. Therefore, C. elegans will provide a great opportunity to identify therapeutic drugs and their targets, as well as to understand mechanisms underlying the formation of cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5101-5104
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• 2012

Background: Genetic mutation is a significant factor in colon CA pathogenesis. Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary disease characterized by multiple colorectal adenomatous polyps affecting a number of cases in the family. This report focuses on a family with attenuated familial adenomatous polyposis (AFAP) with exon 4 mutation, c.481C>T p.Q161X of the APC gene. Methods: We analyzed 20 members of a family with AFAP. Clinical and endoscopic data were collected for phenotype determination. Genetic analysis was also performed by direct sequencing of the APC gene. Result: Five patients with a phenotype of AFAP were found. Endoscopic polyposis was demonstrated among the second generation with genotype mutation of the disease (age > 50 years) consistent with delayed phenotypic adenomatous polyposis in AFAP. APC gene mutation was identified in exon 4 of the APC gene, with mutation points of c.481C>T p.Q161X. Laparoscopic subtotal colectomy was performed to prevent carcinogenesis. Conclusion: A family with attenuated familial adenomatous polyposis of APC related to exon 4 mutation, c.481C>T p.Q161X, was reported and the phenotypic finding was confirmed by endoscopic examination. Genetic mutation analysis might be advantageous in AFAP for long term colon cancer prevention and management due to subtle or asymptomatic phenotype presentation in early adulthood.

• Annals of Pediatric Endocrinology and Metabolism
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• v.23 no.4
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• pp.220-225
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• 2018

Androgen insensitivity syndrome (AIS) is a rare genetic disease caused by various abnormalities in the androgen receptor (AR). The AR is an essential steroid hormone receptor that plays a critical role in male sexual differentiation and development and preservation of the male phenotype. Mutations in the AR gene on the X chromosome cause malfunction of the AR so that a 46,XY karyotype male has some physical characteristics of a woman or a full female phenotype. Depending on the phenotype, AIS can be classified as complete, partial or mild. Here, we report 2 cases of complete AIS in young children who showed complete sex reversal from male to female as a result of AR mutations. They had palpable inguinal masses and normal female external genitalia, a blind-end vagina and absent $M{\ddot{u}}llerian$ duct derivatives. They were both 46,XY karyotype and AR gene analysis demonstrated pathologic mutations in both. Because AIS is inherited in an X-linked recessive manner, we performed genetic analysis of the female family members of each patient and found the same mutation in the mothers of both patients and in the female sibling of case 2. Gonadectomy was performed in both patients to avoid the risk of malignancy in the undescended testicles, and estrogen replacement therapy is planned for their adolescence. Individuals with complete AIS are usually raised as females and need appropriate care.

• Mycobiology
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• v.38 no.1
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• pp.26-32
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• 2010

The cyclic AMP (cAMP) pathway plays a major role in growth, sexual differentiation, and virulence factor synthesis of pathogenic fungi. In Cryptococcus neoformans, perturbation of the cAMP pathway, such as a deletion in the gene encoding adenylyl cyclase (CAC1), causes defects in the production of virulence factors, including capsule and melanin production, as well as mating. Previously, we performed a comparative transcriptome analysis of the Ras- and cAMP- pathway mutants, which revealed 163 potential cAMP-regulated genes (38 genes at a 2-fold cutoff). The present study characterized the role of one of the cAMP pathway-dependent genes (serotype A identification number CNAG_ 06576.2). The expression patterns were confirmed by Northern blot analysis and the gene was designated cAMP-regulated gene 1 (CAR1). Interestingly, deletion of CAR1 did not affect biosynthesis of any virulence factors and the mating process, unlike the cAMP-signaling deficient cac1$\Delta$ mutant. Furthermore, the car1$\Delta$ mutant exhibited wild-type levels of the stress-response phenotype against diverse environmental cues, indicating that Car1, albeit regulated by the cAMP-pathway, is not essential to confer a cAMP-dependent phenotype in C. neoformans.

• Korean Journal of Breeding Science
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• v.42 no.1
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• pp.23-27
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• 2010

The objective of this study was to map the gene for reduced embryo size in rice using DNA markers. The reduced embryo size mutant was induced from N-methyl-N-nitrosourea (MNU) treated Taichung 65. Genetic analysis revealed that the phenotype of the reduced embryo was controlled by a single recessive gene, designated as re-1. For mapping the gene controlling embryo size, an $F_2$ population was developed from a cross between the Korean Tongil-type, Milyang 23 (Oryza sativa ssp. indica) and the mutant. The ratio of $F_2$ seeds nearly fitted to 3:1 ratio, indicating that this phenotype was controlled by a single recessive gene. Bulked sergeant analysis was performed with SSR markers. The gene for the reduced embryo size was detected on chromosome 1. The gene was further mapped between two SSR markers, RM315 and RM265 on chromosome 1 (approximately 1.5 Mb interval). The linked markers will facilitate selection of this grain character in a breeding program and provide the foundation for positional cloning of this gene.

• Animal cells and systems
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• v.2 no.1
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• pp.123-131
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• 1998

The unc-29 region on the chromosome I of Caenorhabditis elegans has been mutagenized in order to obtain lethal mutations. In this screen, the uncoordinated phenotype of unc-29 (e193) mutant was used to identify any lethal mutations closely linked to the unc-29 gene, which encodes a subunit of nicotinic acetylcholine receptors. We have isolated six independent mutations (jh1 to jh6) out of approximately 5,200 ethyl methanesulfonate(EMS) treated haploids. Four of the six mutations demonstrated embryonic lethal phenotypes, while the other two showed embryonic and larval lethal phenotypes. Terminal phenotypes observed in two mutations (jh1 and jh2) indicated developmental defects specific to posterior part of embryos which appeared similar to the phenotypes observed in nob (no back end) mutants. Another mutation (jh4) resulted in an interesting phenotype of body-wall muscle degeneration at larval stage. These mutations were mapped by using three-factor crosses and deficiency mutants in this region. Here we report genetic analysis and characterization of these lethal mutations.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2255-2258
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• 2013

The activity of Rb proteins is controlled by post-translational modifications, especially through phosphorylation. Acetylation of Rb2/p130 was reported recently in NIH3T3 cells but its physiological relevance in cell cycle control and tumorigenesis is still unknown. Efforts are underway to investigate possible interplay between Rb2/p130 phosphorylation and acetylation. Here we hypothesized that Rb2/p130 acetylation, like p53 acetylation, may play a role in development of the tumor phenotype. The proposed hypothesis regarding acetylation of Rb2/p130 in tumor VS normal cells was found to be true in our case study of 36 tumor samples. Statistical analysis of results suggest strong correlation among Rb2/p130 acetylation and cancer phenotype.

• Annals of Clinical Neurophysiology
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• v.11 no.2
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• pp.59-63
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• 2009

Miyoshi myopathy (MM) is caused by the mutations of dysferlin gene (DYSF), which impairs the function of dysferlin protein causing muscle membrane dysfunction. We report a patient showing the MM phenotype who has a sister with LGMD 2B phenotype, along with the results of the immunohistochemical and molecular analyses of the DYSF gene. Immunohistochemical analysis noted negative immunoreactivity against dysferlin. Direct DNA sequencing of whole exons of DYSF gene revealed heterozygous nonsense mutations (c.610C>T + c.2494C>T). To our knowledge, this is the first reported MM case with this very combination of heterozygous mutations.

• Clinical and Experimental Pediatrics
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• v.53 no.10
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• pp.909-912
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• 2010

Familial hypokalemic periodic paralysis is an autosomal-dominant channelopathy characterized by episodic muscle weakness with hypokalemia. The respiratory and cardiac muscles typically remain unaffected, but we report an atypical case of a family with hypokalemic periodic paralysis in which the affected members presented with frequent respiratory insufficiency during severe attacks. Molecular analysis revealed a heterozygous c.664 C>T transition in the sodium channel gene $SCN4A$, leading to an Arg222Trp mutation in the channel protein. The patients described here presented unusual clinical characteristics that included a severe respiratory phenotype, an incomplete penetrance in female carriers, and a different response to medications.