• Clinical and Experimental Pediatrics
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• 제53권3호
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• pp.273-285
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• 2010

Completion of the human genome project has allowed a deeper understanding of molecular pathophysiology and has provided invaluable genomic information for the diagnosis of genetic disorders. Advent of new technologies has lead to an explosion in genetic testing. However, this overwhelming stream of genetic information often misleads physicians and patients into a misguided faith in the power of genetic testing. Moreover, genetic testing raises a number of ethical, legal, and social issues. Diagnostic genetic tests can be divided into three primary but overlapping categories: cytogenetic studies (including routine karyotyping, high-resolution karyotyping, and fluorescent in situ hybridization studies), biochemical tests, and DNA-based diagnostic tests. DNA-based testing has grown rapidly over the past decade and includes preandpostnatal testing for the diagnosis of genetic diseases, testing for carriers of genetic diseases, genetic testing for susceptibility to common non-genetic diseases, and screening for common genetic diseases in a particular population. Theoretically, once a gene's structure, function, and association with a disease are well established, the clinical application of genetic testing should be feasible. However, for routine applications in a clinical setting, such tests must satisfy a number of criteria. These criteria include an acceptable degree of clinical and analytical validity, support of a quality assurance program, possibility of modifying the course of the diagnosed disease with treatment, inclusion of pre-and postnatal genetic counseling, and determination of whether the proposed test satisfies cost-benefit criteria and should replace or complement traditional tests. In the near future, the application of genetic testing to common diseases is expected to expand and will likely be extended to include individual pharmacogenetic assessments.

• Childhood Kidney Diseases
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• 제28권1호
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• pp.8-15
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• 2024

With the rapid evolution of diagnostic tools, particularly next-generation sequencing, the identification of genetic diseases, predominantly those with pediatric-onset, has significantly advanced. However, this progress presents challenges that span from selecting appropriate tests to the final interpretation of results. This review examines various genetic testing methodologies, each with specific indications and characteristics, emphasizing the importance of selecting the appropriate genetic test in clinical practice, taking into account factors like detection range, cost, turnaround time, and specificity of the clinical diagnosis. Interpretation of variants has become more challenging, often requiring further validation and significant resource allocation. Laboratories primarily classify variants based on the American College of Medical Genetics and Genomics and the Association for Clinical Genomic Science guidelines, however, this process has limitations. This review underscores the critical role of clinicians in matching patient phenotypes with reported genes/variants and considering additional factors such as variable expressivity, disease pleiotropy, and incomplete penetrance. These considerations should be aligned with specific gene-disease characteristics and segregation results based on an extended pedigree. In conclusion, this review aims to enhance understanding of the complexities of clinical genetic testing, advocating for a multidisciplinary approach to ensure accurate diagnosis and effective management of rare genetic diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5353-5361
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• 2012

Interleukin-18 (IL-18) is an immune-stimulatory cytokine with antitumor activity in preclinical models. It plays pivotal roles in linking inflammatory immune responses and tumor progression and is a useful candidate in gene therapy of lymphoma or lymphoid leukemia. A phase I study of recombinant human IL-18 (rhIL-18) in patients with advanced cancer concluded that rhIL-18 can be safely given in biologically active doses to patients with advanced cancer. Some viruses can induce the secretion of IL-18 for immune evasion. The individual cytokine activity might be potentiated or inhibited by combinations of cytokines. Here we focus on combinational effects of cytokines with IL-18 in cancer progression. IL-18 is an important non-invasive marker suspected of contributing to metastasis. Serum IL-18 may a useful biological marker as independent prognostic factor of survival. In this review we cover roles of IL-18 in immune evasion, metastasis and angiogenesis, applications for chemotherapy and prognostic or diagnostic significance.

• Journal of Genetic Medicine
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• 제9권2호
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• pp.67-72
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• 2012

The generation of induced pluripotent stem cells (iPSCs) derived from patients' somatic cells provides a new paradigm for studying human genetic diseases. Human iPSCs which have similar properties of human embryonic stem cells (hESCs) provide a powerful platform to recapitulate the disease-specific cell types by using various differentiation techniques. This promising technology has being realized the possibility to explore pathophysiology of many human genetic diseases at the molecular and cellular levels. Furthermore, disease-specific human iPSCs can also be used for patient-based drug screening and new drug discovery at the stage of the pre-clinical test in vitro. In this review, we summarized the concept and history of cellular reprogramming or iPSC generation and highlight recent progresses for disease modeling using patient-specific iPSCs.

• Journal of Genetic Medicine
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• 제19권2호
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• pp.57-62
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• 2022

Systemic autoinflammatory diseases (SAIDs) are characterized by unprovoked inflammatory episodes such as recurrent/periodic fever, serositis, skin lesions, abdominal symptoms, arthritis/arthralgia, and central nervous system involvement. Genetic diagnosis of SAIDs has been challenging because disease manifestations overlap among themselves and with other immunological disease categories, such as infection and autoimmune diseases. However, the advent of next-generation sequencing (NGS) technologies and expanding knowledge about the innate immunity and inflammation have made the routine genetic diagnosis of SAIDs possible. Here, we review the recurrent/periodic fevers, other recently identified autoinflammatory diseases, and type I interferonopathies, and discuss the clinical usefulness of NGS targeted sequencing for SAIDs, and recent advance of understandings for this heterogeneous disease group as for underlying primary immunodeficiency.

• Journal of Genetic Medicine
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• 제21권1호
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• pp.1-5
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• 2024

Despite advances in the diagnosis and management of rare diseases (RDs), there remains a tendency to overlook adult RD patients. In addition to the considerable number of adult-onset RDs, advances in the diagnosis and management of pediatric RDs have led to an increase in the survival of these patients into adulthood. Adult RDs exhibit distinct features from pediatric counterparts, necessitating careful consideration during medical assessments. Given the extended life expectancy of adult RD patients, precise diagnosis and management strategies can significantly enhance patient outcomes. This review aims to provide an in-depth exploration of the characteristics unique to adult RDs. Special emphasis will be placed on the importance of cascade screening and prenatal genetic testing in the context of adult RDs, highlighting the need for a comprehensive understanding of these aspects in clinical practice.

• 농업과학연구
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• 제32권1호
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• pp.53-61
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• 2005

한국의 소 사육 농가에서 유전병을 monitoring 하는 체계가 현재 존재하지 않기 때문에 정확히 한우에서 어떤 유전병이 존재하는지 알 수가 없는 실정이다. 최근에 일본에서는 흑모화우에 존재하는 유전병을 제거하기 위해 많은 노력을 들이고 있다. 본 연구는 일본의 흑모화우에 존재하는 유전병인 Band 3와 CHS의 존재 유무를 혈연관계가 없는 한우 22개체를 이용하여 PCR-RFLP 방법으로 확인하였다. 비록 한우에서 Band 3와 CHS 유전병을 가진 개체는 나오지 않았으나 본 연구에서 확립된 방법을 한우 보증 종모우와 후보 종모우에서 확인하여 유전병을 가진 유전자가 다음 세대로 전달되는 것을 막을 필요성이 있다.

• Journal of Genetic Medicine
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• 제7권1호
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• pp.16-23
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• 2010

많은 내분비 질환이 유전적 요소를 갖고 있다. 단일 유전자 질환에서는 유전적 요인이 주요 원인이나 다인자성 질환에서는 환경과 생활습관 등이 함께 병인으로 작용한다. 유전성 내분비 질환의 분자유전학적 병인에 대한 이해에 대하여 최근 많은 발전이 있어 왔으며 분자유전학적 기술의 응용으로 질환에 대한 이해와 이를 이용한 진단 및 유전 상담에 도움이 되고 있다. 유전학적 검사로 특정 질환의 돌연변이를 증명하는 것은 진단이 모호한 경우에서 정확한 진단과 산전 진단, 보인자 검사에 적용될 수 있다. 그러나 유전자 검사만으로 임신 중절과 관련된 산전 진단에 이용하는 데에는 신중을 기해야 한다.

• Journal of Genetic Medicine
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• 제20권2호
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• pp.39-45
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• 2023

As advanced sequencing technologies continue to uncover an increasing number of variants in genes associated with human genetic diseases, there is a growing demand for systematic approaches to assess the impact of these variants on human development, health, and disease. While in silico analyses have provided valuable insights, it is essential to complement these findings with model organism studies to determine the functional consequences of genetic variants in vivo. Drosophila melanogaster is an excellent genetic model for such functional studies due to its efficient genetic technologies, high gene conservation with humans, accessibility to mutant fly resources, short life cycles, and cost-effectiveness. The traditional GAL4-UAS system, allowing precise control of gene expression through binary regulation, is frequently employed to assess the effects of monoallelic variants. Recombinase medicated cassette exchange or CRISPR-Cas9-mediated GAL4 insertion within coding introns or substitution of gene body with Kozak-Gal4 result in the loss-of-function of the target gene. This GAL4 insertion strategy also enables the expression of reference complementary DNA (cDNA) or cDNA carrying genetic variants under the control of endogenous regulatory cis elements. Furthermore, the CRISPR-Cas9-directed tissue-specific knockout and cDNA rescue system provides the flexibility to investigate candidate variants in a tissue-specific and/or developmental-timing dependent manner. In this review, we will delve into the diverse genetic techniques available in Drosophila and their applications in diagnosing and studying numerous undiagnosed diseases over the past decade.

• 대한유전성대사질환학회지
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• 제5권1호
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• pp.108-115
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• 2005

Inherited metabolic diseases (IMD) comprise a large class of genetic diseases involving disorders of metabolism. The majorities are due to defects of single genes that code for enzymes that facilitate conversion of various substances into others. Because of the multiplicity of conditions, many different diagnostic tests are used for screening of IMD. Molecular genetic diagnosis is the detection of pathogenic mutations in DNA and/or RNA samples and is becoming a much more common practice in medicine today. The purpose of molecular genetic testing in IMD includes diagnostic testing, pre-symptomatic testing, carrier screening, prenatal diagnosis, preimplantation testing, and population screening. However, because of the complexity, difficulty in interpreting the result, and the ethical considerations, an understanding of technical, conceptual, and practical aspects of molecular genetic diagnosis is mandatory.