단일인자 유전과 다인자 유전에 관한 고등학교 생명과학Ⅰ 교과서 내용분석 연구

이성재,전상학 한국생물교육학회 2022 생물교육 Vol.50 No.2

Recently, it has been suggested that some human traits taught as monogenic inheritance are not monogenic traits. This study examined whether the concepts of "monogenic inheritance" and "multifactor inheritance" in the Life ScienceⅠ textbook had any inaccuracies, as well as whether the examples of genetic traits used to explain monogenic inheritance were appropriate. For this research, four major books on biology, genetics, and eight high school life scienceⅠ textbooks were compared to clarify the meaning of two genetic concepts and then four human traits (earlobe attachment, cheek dimple, widow’s peak, and togue rolling) were analyzed by using OMIM, a human trait database, and related literature to determine whether or not they were an appropriate example of monogenic traits. As a result, the term "multifactorial inheritance" was not clearly distinguished between "polygenic" and "multifactorial." In addition, we found that explanations in textbooks could give rise to alternative concepts for both genetic concepts. We also found that there is insufficient literature and studies suggesting that earlobe attachment, cheek dimples, widow’s peak, and tongue rolling are monogenic traits. Therefore, we recommend that some human genetic traits which are widely acknowledged by many scientists and commonly mentioned in biology major books should be primarily considered to teach monogenic inheritance. In conclusion, we hope that this research will be useful in clarifying two ambigous genetic concepts in Life ScienceⅠ textbooks and proposing the direction of textbook revision.

Polygenic risk score for genetic evaluation of prostate cancer risk in Asian populations: A narrative review

송상헌,변석수 대한비뇨의학회 2021 Investigative and Clinical Urology Vol.62 No.3

Decreasing costs of genetic testing and interest in disease inheritance has changed the landscape of cancer prediction in prostate cancer (PCa), and guidelines now include genetic testing for high-risk groups. Familial and hereditary PCa comprises approximately 20% and 5% of all PCa, respectively. Multifaceted disorders like PCa are caused by a combinatory effect of rare genes of high penetrance and smaller genetic variants of relatively lower effect size. Polygenic risk score (PRS) is a novel tool utilizing PCa-associated single nucleotide polymorphisms (SNPs) identified from genome-wide association study (GWAS) to generate an additive estimate of an individual's lifetime genetic risk for cancer. However, most PRS are developed based on GWAS collected from mainly European populations and do not address ethnic differences in PCa genetics. This review highlights the attempts to generate a PRS tailored to Asian males including data from Korea, China, and Japan, and discuss the clinical implications for prediction of early onset and aggressive PCa.

가족내 발생한 모야모야병

정승률,서동환,김무성,이선일,정용태,김수천,심재홍 대한신경외과학회 1998 Journal of Korean neurosurgical society Vol.27 No.12

Genetic approaches toward understanding the individual variation in cardiac structure, function and responses to exercise training

Minsun Kim,Seung Kyum Kim 대한약리학회 2021 The Korean Journal of Physiology & Pharmacology Vol.25 No.1

Cardiovascular disease (CVD) accounts for approximately 30% of all deaths worldwide and its prevalence is constantly increasing despite advancements in medical treatments. Cardiac remodeling and dysfunction are independent risk factors for CVD. Recent studies have demonstrated that cardiac structure and function are genetically influenced, suggesting that understanding the genetic basis for cardiac structure and function could provide new insights into developing novel therapeutic targets for CVD. Regular exercise has long been considered a robust nontherapeutic method of treating or preventing CVD. However, recent studies also indicate that there is inter-individual variation in response to exercise. Nevertheless, the genetic basis for cardiac structure and function as well as their responses to exercise training have yet to be fully elucidated. Therefore, this review summarizes accumulated evidence supporting the genetic contribution to these traits, including findings from population-based studies and unbiased large genomic-scale studies in humans.

Prediction of clinically significant prostate cancer using polygenic risk models in Asians

송상헌,김은애,우은진,권은경,윤성로,김정권,이학민,오종진,이상철,홍성규,변석수 대한비뇨의학회 2022 Investigative and Clinical Urology Vol.63 No.1

Purpose: To develop and evaluate the performance of a polygenic risk score (PRS) constructed in a Korean male population to predict clinically significant prostate cancer (csPCa). Materials and Methods: Total 2,702 PCa samples and 7,485 controls were used to discover csPCa susceptible single nucleotide polymorphisms (SNPs). Males with biopsy-proven or post-radical prostatectomy Gleason score 7 or higher were included for analysis. After genotype imputation for quality control, logistic regression models were applied to test association and calculate effect size. Extracted candidate SNPs were further tested to compare predictive performance according to number of SNPs included in the PRS. The best-fit model was validated in an independent cohort of 311 cases and 822 controls. Results: Of the 83 candidate SNPs with significant PCa association reported in previous literature, rs72725879 located in PRNCR1 showed the highest significance for PCa risk (odds ratio, 0.597; 95% confidence interval [CI], 0.555–0.641; p=4.3×10-45). Thirty-two SNPs within 26 distinct loci were further selected for PRS construction. Best performance was found with the top 29 SNPs, with AUC found to be 0.700 (95% CI, 0.667–0.734). Males with very-high PRS (above the 95th percentile) had a 4.92-fold increased risk for csPCa. Conclusions: Ethnic-specific PRS was developed and validated in Korean males to predict csPCa susceptibility using the largest csPCa sample size in Asia. PRS can be a potential biomarker to predict individual risk. Future multi-ethnic trials are required to further validate our results.

Cancer Risk Score Prediction Based on a Single-Nucleotide Polymorphism Network

Bharuno Mahesworo,Arif Budiarto,Alam Ahmad Hidayat,Bens Pardamean 대한의료정보학회 2022 Healthcare Informatics Research Vol.28 No.3

Objectives: Genome-wide association studies (GWAS) are performed to study the associations between genetic variants withrespect to certain phenotypic traits such as cancer. However, the method that is commonly used in GWAS assumes that certaintraits are solely affected by a single mutation. We propose a network analysis method, in which we generate associationnetworks of single-nucleotide polymorphisms (SNPs) that can differentiate case and control groups. We hypothesize thatcertain phenotypic traits are attributable to mutations in groups of associated SNPs. Methods: We propose a method basedon a network analysis framework to study SNP-SNP interactions related to cancer incidence. We employed logistic regressionto measure the significance of all SNP pairs from GWAS for the incidence of colorectal cancer and computed a cancer riskscore based on the generated SNP networks. Results: We demonstrated our method in a dataset from a case-control studyof colorectal cancer in the South Sulawesi population. From the GWAS results, 20,094 pairs of 200 SNPs were created. Weobtained one cluster containing four pairs of five SNPs that passed the filtering threshold based on their p-values. A locus onchromosome 12 (12:54410007) was found to be strongly connected to the four variants on chromosome 1. A polygenic riskscore was computed from the five SNPs, and a significant difference in colorectal cancer risk was obtained between the caseand control groups. Conclusions: Our results demonstrate the applicability of our method to understand SNP-SNP interactionsand compute risk scores for various types of cancer.

Omic Approach in Non-smoker Female with Lung Squamous Cell Carcinoma Pinpoints to Germline Susceptibility and Personalized Medicine

Margherita Baldassarri,Chiara Fallerini,Francesco Cetta,Marco Ghisalberti,Cristiana Bellan,Simone Furini,Ottavia Spiga,Sergio Crispino,Giuseppe Gotti,Francesca Ariani,Piero Paladini,Alessandra Renieri 대한암학회 2018 Cancer Research and Treatment Vol.50 No.2

Purpose Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. Materials and Methods A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibs were subjected to a novel integrative “omic” approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger. A first-step whole-exome sequencing on tumor and normal tissue did not identify mutations in known driver genes. Building on the idea of a germline oligogenic origin of lung cancer, we performed whole-exome sequencing of DNA from patients’ peripheral blood and their unaffected sibs. Finally, RNA-sequencing analysis in tumoral and matched non-tumoral tissues was carried out in order to investigate the clonal profile and the pathogenic role of the identified variants. Results Filtering for rare variants with Combined Annotation Dependent Depletion (CADD) > 25 and potentially damaging effect, we identified rare/private germline deleterious variants in 11 cancer-associated genes, none of which, except one, shared with the healthy sib, pinpointing to a “private” oligogenic germline signature. Noteworthy, among these, two mutated genes, namely ACACA and DEPTOR, turned to be potential targets for therapy because related to known drivers, such as BRCA1 and EGFR. Conclusion In the era of precision medicine, this report emphasizes the importance of an “omic” approach to uncover oligogenic germline signature underlying cancer development and to identify suitable therapeutic targets as well.