Noninvasive Testing for Colorectal Cancer Screening: Where Are We Now?

천재영,김지현,윤영훈,박효진 대한소화기암연구학회 2023 Journal of Digestive Cancer Research (JDCR) Vol.11 No.2

Colorectal cancer (CRC) is one of the most prevalent cancers and is the leading cause of cancerrelated mortality worldwide. Based on the current screening guidelines by the American Cancer Society and Korean multi-society expert committee, CRC screening is recommended in asymptomatic adults starting at the age of 45 years. Fecal immunochemical test-based screening programs reduce the development of CRC and related mortality in the general population. However, this most popular CRC screening strategy demonstrates a crucial limitation due to modest diagnostic accuracy. Colonoscopy may be considered as an alternative primary method for CRC screening; however, its implementation can still be challenging due to concerns regarding invasiveness, low adherence, cost-effectiveness, and quality assurance. To overcome the limitations of current screening tests, innovative noninvasive tests for CRC screening have been developed with advances in molecular biology, genetics, epigenetics, and microbiomics for detecting CRC, which may enhance the approach to CRC screening and diagnosis in clinical practice in the near future. This review explores the emerging screening methods and discusses their potential for integration into current practice.

블로그를 통해 본 산전 기형아 검사와 양수검사에 대한 질문과 댓글 분석

전명희(Myunghee Jun),신계영(Gyeyoung Shin),최경숙(Kyung Sook Choi) 한국콘텐츠학회 2015 한국콘텐츠학회논문지 Vol.15 No.3

본 연구의 목적은 블로그에 나타난 임신 여성의 산전 기형아 검사 및 양수검사 관련 교육요구를 파악하기 위하여 총 7개의 국내 인터넷 블로그를 분석하였다. 본 연구는 두 단계로 이루어졌다. 1 단계는 2011년 10월 31일까지 6년간 7개 블로그 중 6개 블로그에 게시된 내용 중 산전 기형아 검사 389건을 통하여 연구의 분석 틀을 마련하였다. 2 단계에서는 ‘맘스홀릭 베이비’에 게시된 산전 기형아 검사에 관한 질문 100건, 양수 검사에 관한 질문 200건과 댓글 1,665건을 2011년 12월 텍스트화하고 산전 기형아 검사와 양수검사의 건수, 검사 이유 및 검사와 관련된 문제점을 분석하였다. 그 결과, 임신부들은 산전 기형아 검사와 양수검사와 관련하여 검사의 용어, 목적 및 임신 주수에 따른 검사 지식이 부족하였고, 양수 검사를 권유 받은 임신부 중 56.5%가 불안과 두려움을 호소하였다. 양수검사에 관한 찬성과 반대 건수를 분석한 결과, 찬성 보다는 반대 건수가 더 많았고, 양수검사를 권유 받은 자 중 33.9%는 양수검사를 받지 않았다. 이상의 결과에서 보듯이 의료 기관 서비스 안에서 임신 여성과 가족들에게 임신 주수에 따른 산전 기형아 검사에 관한 교육 및 지지가 강화될 필요가 있다. 이를 위하여 산전 클리닉 외래의 상담 및 교육 서비스 기능을 강화하고, 유전 상담전문가를 추가로 배치할 필요가 있으며 인터넷 보급률 증가와 현대 임신 여성이 선호하는 커뮤니케이션 방식을 고려하여 온라인 건강 정보 사이트 운영 및 콘텐츠 개발에 관심을 기울일 필요가 있다. 또한 본 연구결과는 기형아 검사 후 낙태 허용범위 기준에 대한 논의 시 기초자료로 활용될 수 있을 것이다. The purpose of this study was to identify pregnant women’s needs for information on prenatal genetic diagnosis and screening. This study is consisted of two phases. In the first phase in December 2011, six blogs featuring questions and answers on prenatal genetic diagnosis and screening were selected from four major search engines in Korea by using the keywords “prenatal genetic diagnosis,” “prenatal genetic screening”, and “amniocentesis.” An analyzing framework was constructed on the basis of 389 posts on six blogs between November 2006 and October 2011. In the second phase, the contents of the “MomsHolicbaby” blog posted from November 2010 to October 2011 were reviewed. Then, pregnant women’s questions on prenatal genetic diagnosis and screening (100 questions) and amniocentesis (200 questions with 1,665 answers) were analyzed using descriptive statistics. Among posters who had ever been recommended to undergo amniocentesis, 56.5% described feelings of anxiety, 25.5% did not know the purpose of the test, and 33.9% refused to undergo the test. Among 295 posters answering questions about amniocentesis, 61.4% disagreed with undergoing the test. The results show that there is a need for healthcare professionals to provide more educational and emotional support to pregnant women considering prenatal genetic diagnosis and screening. Providing online health information can be integrated into prenatal genetic education for pregnant women as well as nurses. In addition, prenatal women’s preferences about undergoing amniocentesis should be reflected in the current legal discussion on criteria for termination of pregnancy.

Genetics of Prader-Willi syndrome and Prader-Will-Like syndrome

전종근 대한소아내분비학회 2016 Annals of Pediatirc Endocrinology & Metabolism Vol.21 No.3

The Prader-Willi syndrome (PWS) is a human imprinting disorder resulting from genomic alterations that inactivate imprinted, paternally expressed genes in human chromosome region 15q11-q13. This genetic condition appears to be a contiguous gene syndrome caused by the loss of at least 2 of a number of genes expressed exclusively from the paternal allele, including SNRPN, MKRN3, MAGEL2, NDN and several snoRNAs, but it is not yet well known which specific genes in this region are associated with this syndrome. Prader-Will-Like syndrome (PWLS) share features of the PWS phenotype and the gene functions disrupted in PWLS are likely to lie in genetic pathways that are important for the development of PWS phenotype. However, the genetic basis of these rare disorders differs and the absence of a correct diagnosis may worsen the prognosis of these individuals due to the endocrine-metabolic malfunctioning associated with the PWS. Therefore, clinicians face a challenge in determining when to request the specific molecular test used to identify patients with classical PWS because the signs and symptoms of PWS are common to other syndromes such as PWLS. This review aims to provide an overview of current knowledge relating to the genetics of PWS and PWLS, with an emphasis on identification of patients that may benefit from further investigation and genetic screening.

Next-generation libraries for robust RNA interference-based genome-wide screens

Kampmann, Martin,Horlbeck, Max A.,Chen, Yuwen,Tsai, Jordan C.,Bassik, Michael C.,Gilbert, Luke A.,Villalta, Jacqueline E.,Kwon, S. Chul,Chang, Hyeshik,Kim, V. Narry,Weissman, Jonathan S. National Academy of Sciences 2015 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.112 No.26

<P><B>Significance</B></P><P>Genetic screening is a classic approach to identify genes acting in a biological process of interest. In mammalian cells, screens are commonly based on RNA interference (RNAi), in which a short interfering RNA (siRNA) or short-hairpin RNA (shRNA) triggers degradation of cellular messenger RNAs. RNAi approaches are prone to false-positive results because of siRNA/shRNA off-target effects and false-negative results because of siRNAs/shRNAs lacking activity. We previously established that these problems can be minimized with ultracomplex shRNA libraries. Here, we present next-generation shRNA libraries targeting the human and mouse genomes, for which we improved several features to increase shRNA activity. In a pilot screen, the new library yields complementary results to clustered regularly interspaced short palindromic repeats interference (CRISPRi), an orthogonal approach we developed recently.</P><P>Genetic screening based on loss-of-function phenotypes is a powerful discovery tool in biology. Although the recent development of clustered regularly interspaced short palindromic repeats (CRISPR)-based screening approaches in mammalian cell culture has enormous potential, RNA interference (RNAi)-based screening remains the method of choice in several biological contexts. We previously demonstrated that ultracomplex pooled short-hairpin RNA (shRNA) libraries can largely overcome the problem of RNAi off-target effects in genome-wide screens. Here, we systematically optimize several aspects of our shRNA library, including the promoter and microRNA context for shRNA expression, selection of guide strands, and features relevant for postscreen sample preparation for deep sequencing. We present next-generation high-complexity libraries targeting human and mouse protein-coding genes, which we grouped into 12 sublibraries based on biological function. A pilot screen suggests that our next-generation RNAi library performs comparably to current CRISPR interference (CRISPRi)-based approaches and can yield complementary results with high sensitivity and high specificity.</P>

최신임상강좌 : 산전 선별검사의 해석

박인양 ( In Yang Park ),권지영 ( Ji Young Kwon ),신종철 ( Jong Chul Shin ) 대한산부인과학회 2009 Obstetrics & Gynecology Science Vol.52 No.2

태아 홑배수체의 확진을 위해서는 융모막생검이나 양수검사, 탯줄천자와 같은 진단과정이 필요하다. 그러나 이 경우 태아유산과 같은 합병증 발생 위험이 있기 때문에 위양성률을 줄이면서 진단율을 높일 수 있는 효과적인 선별검사의 개발이 매우 중요하다. 염색체이상을 선별하기 위한 산전검사는 모체혈청표지자검사와 초음파검사로 분류할 수 있다. 모체혈청표지자검사에는 임신 제2삼분기의 다중표지자검사뿐만 아니라 임신 제1삼분기에 목덜미투명대 두께와 혈청검사의 병행검사가 있다. 이외에도 제1삼분기와 제2삼분기의 혈청 표지자검사와 목덜미투명대 두께를 종합하여 다운증후군의 발견율을 높이는 방법들이 가능하다. 유전적초음파검사는 구조적 이상인 주기형과 초음파 표지자를 발견하는 과정으로 주로 임신 제2삼분기에 시행한다. 불필요한 침습적 진단방법을 줄이면서 태아 염색체이상 고위험군의 발견율을 높이기 위해서는 산모 연령, 임신 제1삼분기의 혈청검사, 목덜미투명대 두께, 임신 제2삼분기의 다중표지자검사 그리고 유전적초음파검사결과에 대한 정확한 해석 및 통합적인 고려가 중요하다. For definitive antenatal diagnosis of fetal aneuploidy, invasive tests such as chorionic villous sampling, amniocentesis and cordocentesis are required for chromosome analysis. However, to reduce the risk of miscarriage associated with procedural complications, it is important to detect pregnant women with high risk of fetal aneuploidy. Recently, there have been advances in maternal serum and sonographic markers for screening of chromosomal defects in the first and second trimester. The serum screening methods include first trimester screening with nuchal translucency and second trimester multi marker screening. Particularly, combining first and second trimester results can increase the detection rate of Down syndrome with lower false-positive rates. In addition to biochemical markers, second trimester sonogram to detect major and minor sonographic markers for chromosomal defects is important to identify the high risk pregnancy. To detect the fetal aneuploidy with high specificity and sensitivity, we need to interpret the maternal age, the results of first and second trimester serum markers and genetic sonographic findings all together.

Genetically Encoded Biosensors for the GR-effector Screening

Chungwon KANG,Youngeun KWON 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10

Cortisol plays an essential role in mediating stress and anti-inflammatory response. It is important to screen cortisol and its analogues to monitor stress levels and identify drug candidates. Novel cell-based biosensors have arisen as a promising platform for detecting targets. We used a glucocorticoid receptor (GR) fused split-intein and a counterpart split-intein pair, separated by a cellular compartment to fabricate sensor cells. Cortisol triggered conditional protein splicing (CPS) translocates fluorescence cargo to cytosol from the nucleus. The sensor cells showed exceptional performance with fast detection and discriminating functional analogues from the structural analogues of cortisol. The sensor cells can detect unknown GR-effectors in essential oils. Peppermint oil was revealed to contain GR-effector, and L-limonene was identified. Further analysis indicated L-limonene as a selective GR agonist, a potent anti-inflammatory agent that attenuates inflammatory response without causing notable adverse effects. The cell-based biosensor provides a valuable platform for GR-effector screening. It also suggests detecting targets in the native context, which holds large potential in drug discovery.

Xylella fastidiosa의 배양여액을 이용한 포도나무 피어스병 품종 저항성 검정

박명수,윤해근,Park, Myung Soo,Lu, Jiang,Yun, Hae Keun 한국식물생명공학회 2017 식물생명공학회지 Vol.44 No.4

포도나무 피어스병에 대한 품종간 저항성을 검정하는 데에 이용되는 병원균 접종법이나 포장저항성 검정법을 대체할 수 있는 방법으로 병원균(Xylella fastidiosa)이 생산하는 배양여액을 이용할 수 있는 검정법을 개발하고자 하였다. 상처를 가한 포도나무 잎에 병원균의 배양여액을 처리한 결과 독성이 발현되었으며 품종간에 차이가 나타났다. 병원균 배양여액의 에틸아세테이트 추출물은 공시한 포도나무에서 배양여액 처리와 동일한 반응을 유도하였다. 병원균 배양여액의 독성과 감수성은 에틸아세테이트 추출물과 동일하였다. 감수성 품종은 높은 비율로 희석된 배양여액에도 감수성을 나타내었으며, 저항성품종은 원액에서도 반응하지 않았다. 감수성 품종은 희석된 배양여액보다 원액에서 감수성이었으나 저항성 품종은 원액에도 저항성을 나타내었다. 본 연구에서 유럽종 포도 품종이 중도 감수성이었으나, 배양여액을 이용한 피어스병해 저항성 검정은 병해에 저항성인 유전자원 선발과, 교배조합의 저항성 실생의 조기에 선발에 중요한 기술로서, 향후 병해에 저항성인 포도품종 육성에 크게 기여할 것으로 여겨진다. This study investigated whether culture filtrates produced by Xylella fastidiosa can be used to determine the varietal susceptibility to Pierce's disease in grapevines (Vitis spp.) as a substitute for pathogen inoculation or field screening. A bioassay of grape leaves with culture filtrates from the pathogen showed that their phytotoxicities were active and host-selective. Ethyl acetate extracts from them also showed toxicities and host selectivity in both bunches of grapes and muscadine grapes. The sensitive range of plants to the culture filtrates and their ethyl acetate extracts was consistent with the host range of the Pierce's disease pathogen. Susceptible cultivars are sensitive to even highly diluted culture filtrates, while resistant cultivars were not affected even at their original culture filtrates. Susceptible cultivars were more sensitive to the undiluted culture filtrate than were highly diluted culture filtrates, and the younger leaves were the most sensitive to the culture filtrates in grapes. Although some European grape cultivars showed moderately susceptibility in this study, the determination of varietal resistance to Pierce's disease by the treatment of culture filtrates of pathogens could provide valuable information for the preliminary selection of genetic resources and seedlings from hybridization in a disease resistant grape breeding program.

Xylella fastidiosa의 배양여액을 이용한 포도나무 피어스병 품종 저항성 검정

박명수,Jiang Lu,윤해근 한국식물생명공학회 2017 JOURNAL OF PLANT BIOTECHNOLOGY Vol.44 No.4

This study investigated whether culture filtrates produced by Xylella fastidiosa can be used to determine the varietal susceptibility to Pierce's disease in grapevines (Vitis spp.) as a substitute for pathogen inoculation or field screening. A bioassay of grape leaves with culture filtrates from the pathogen showed that their phytotoxicities were active and host-selective. Ethyl acetate extracts from them also showed toxicities and host selectivity in both bunches of grapes and muscadine grapes. The sensitive range of plants to the culture filtrates and their ethyl acetate extracts was consistent with the host range of the Pierce’s disease pathogen. Susceptible cultivars are sensitive to even highly diluted culture filtrates, while resistant cultivars were not affected even at their original culture filtrates. Susceptible cultivars were more sensitive to the undiluted culture filtrate than were highly diluted culture filtrates, and the younger leaves were the most sensitive to the culture filtrates in grapes. Although some European grape cultivars showed moderately susceptibility in this study, the determination of varietal resistance to Pierce’s disease by the treatment of culture filtrates of pathogens could provide valuable information for the preliminary selection of genetic resources and seedlings from hybridization in a disease resistant grape breeding program.

Target Identification: A Challenging Step in Forward Chemical Genetics

Das, Raj Kumar,Samanta, Animesh,Ghosh, Krishnakanta,Zhai, Duanting,Xu, Wang,Su, Dongdong,Leong, Cheryl,Chang, Young-Tae Korean Society for Bioinformatics 2011 Interdisciplinary Bio Central (IBC) Vol.3 No.1

Investigation of the genetic functions in complex biological systems is a challenging step in recent year. Hence, several valuable and interesting research projects have been developed with novel ideas to find out the unknown functions of genes or proteins. To validate the applicability of their novel ideas, various approaches are built up. To date, the most promising and commonly used approach for discovering the target proteins from biological system using small molecule is well known a forward chemical genetics which is considered to be more convenient than the classical genetics. Although, the forward chemical genetics consists of the three basic components, the target identification is the most challenging step to chemical biology researchers. Hence, the diverse target identification methods have been developed and adopted to disclose the small molecule bound protein. Herein, in this review, we briefly described the first two parts chemical toolbox and screening, and then the target identifications in forward chemical genetics are thoroughly described along with the illustrative real example case study. In the tabular form, the different biological active small molecules which are the successful examples of target identifications are accounted in this research review.

Genetic Variants and Clinical Phenotypes in Korean Patients With Hereditary Hemorrhagic Telangiectasia

김보경,정주현,김미정,문은혜,오재환,박정우,차흥억,김주현,김윤재,정준원,함기백,진홍률,장용주,김성완,정승규,김대우,이영재,김선태 대한이비인후과학회 2021 Clinical and Experimental Otorhinolaryngology Vol.14 No.4

Objectives. Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by recurrent epistaxis, telangiectasia, and visceral arteriovenous malformations (AVMs). Activin A receptor-like type 1 (ACVRL1/ALK1) and endoglin (ENG) are the principal genes whose mutations cause HHT. No multicenter study has yet investigated correlations between genetic variations and clinical outcomes in Korean HHT patients. Methods. Seventy-two members from 40 families suspected to have HHT based on symptoms were genetically screened for pathogenic variants of ACVRL1 and ENG. Patients with genetically diagnosed HHT were also evaluated. Results. In the HHT genetic screening, 42 patients from 24 of the 40 families had genetic variants that met the pathogenic criteria (pathogenic very strong, pathogenic strong, pathogenic moderate, or pathogenic supporting) based on the American College of Medical Genetics and Genomics Standards and Guidelines for either ENG or ACVRL1: 26 from 12 families (50%) for ENG, and 16 from 12 families (50%) for ACVRL1. Diagnostic screening of 42 genetically positive HHT patients based on the Curaçao criteria revealed that 24 patients (57%) were classified as having definite HHT, 17 (41%) as having probable HHT, and 1 (2%) as unlikely to have HHT. Epistaxis was the most common clinical presentation (38/42, 90%), followed by visceral AVMs (24/42, 57%) and telangiectasia (21/42, 50%). Five patients (12%) did not have a family history of HHT clinical symptoms. Conclusion. Only approximately half of patients with ACVRL1 or ENG genetic variants could be clinically diagnosed as having definite HHT, suggesting that genetic screening is important to confirm the diagnosis.