Journal of translational genetics and genomics最新文献

{"title":"Wide-field optical coherence tomography in ABCA4-associated inherited retinal dystrophies","authors":"M. Saleh, H. Stöhr, C. Kiel, S. Kellner, S. Weinitz, Ghazaleh Farmand, B. Weber, A. Lommatzsch, U. Kellner","doi":"10.20517/jtgg.2021.23","DOIUrl":"https://doi.org/10.20517/jtgg.2021.23","url":null,"abstract":".","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43364960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenetic influences on the response to pharmacological treatment in autism spectrum disorders","authors":"A. Hervás, Alexandre Serra-LLovich, I. Rueda, I. Targa, Silvina Guijarro, Aitana Bigorra, Martha Cancino, V. Bote, M. Cárcel, Nare Amasi-Hartoonian, Marta H Hernandez, M. Arranz","doi":"10.20517/jtgg.2021.25","DOIUrl":"https://doi.org/10.20517/jtgg.2021.25","url":null,"abstract":"Aim: About a third of patients with autism spectrum disorder (ASD) receive pharmacological treatment for comorbid symptoms. However, 30%-50% do not respond adequately and/or present severe and long-lasting side effects. Previous studies have reported the influence of variants in genes coding for drug targets on the efficacy and safety of pharmacological treatments, including genetic polymorphisms in dopaminergic and serotonergic systems. However, most studies have focused on the adult population, with relatively few studies in children and adolescents, and no clear biomarkers of response have been reported in these populations. The aim of our study was to identify genetic predictors of drug response in patients with ASD. This information may be used to personalise pharmacological treatment and improve the efficacy and safety of psychotropic drugs in patients with ASD. Methods: Genetic variants in dopaminergic and serotonergic drug targets ( SLC6A3 , DRD2 , DRDRD3 , DRD4 , HTR2A , and HTR2C ) and in other genes previously associated with treatment efficacy and/or induced side effects ( ANKK1 , BDNF , COMT , and HTR1A ) were investigated in 176 children and adolescents diagnosed with ASD and undergoing pharmacological treatment. Results: A SLC6A3 genetic variant was associated with response to methylphenidate in our ASD cohort, whereas HTR2A and HTR2C allele and haplotype distributions were associated with adverse reactions such as somnolence, mood alterations, and BMI. ANKK1 , COMT , and BDNF genetic variants were mainly associated with treatment side effects. Conclusion: If confirmed, these genetic variants may be used as predictors of clinical outcome and help to personalise pharmacological treatments in patients with ASD. previous study reported this polymorphism associated with insulin-resistance in patients with ASD treated with risperidone [25] . We did not find any significant association with the other dopaminergic variants investigated ( DRD2 rs18012028, DRD3 rs167771 & rs6280, and a 48bp repeat in DRD4 ), although DRD3 haplotype combinations were found nominally associated with shutdowns in the total sample ( P = 0.04) and with side effects in the methylphenidate subgroup ( P = 0.05). Previous studies reported association between the DRD3 rs6280 polymorphism and methylphenidate response in a group of 64 children with ASD [14] and risperidone response in a sample of 45 patients with ASD [15] . These findings require further investigation in larger samples to confirm the possible contribution of DRD3 variants to treatment response variability in ASD.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46184880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between genetic variants in HSD3B1 and clinical management of PCa","authors":"Jingyi Huang, Da Huang, R. Na","doi":"10.20517/jtgg.2021.14","DOIUrl":"https://doi.org/10.20517/jtgg.2021.14","url":null,"abstract":"The Abstract Androgen is an important factor in the occurrence and progression of prostate cancer. The principal clinical strategy is","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45552926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular insight: SERPINB3 and AR sensitivity might reduce the risk of COVID-19 infection and complications in prostate cancer patients receiving androgen-deprivation therapy","authors":"Shiv Verma, Sanjay Gupta","doi":"10.20517/jtgg.2021.30","DOIUrl":"https://doi.org/10.20517/jtgg.2021.30","url":null,"abstract":"© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43750086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disparities in acute lymphoblastic leukemia risk and survival across the lifespan in the United States of America","authors":"Keren Xu, Qianxi Feng, J. Wiemels, Adam J. Smith","doi":"10.20517/jtgg.2021.20","DOIUrl":"https://doi.org/10.20517/jtgg.2021.20","url":null,"abstract":"Acute lymphoblastic leukemia (ALL) most less in and young adults (AYAs) is among older adults. The 5-year survival of is above 90% in children, drops significantly in AYAs, and over half of ALL-related deaths occur in older adults. In addition to diagnosis age, the race/ethnicity of patients consistently shows association with ALL incidence and outcomes. we review the racial/ethnic disparities in ALL incidence and outcomes, discuss how these vary across the age spectrum, and examine the potential causes of these disparities. In the United States, the incidence of ALL is highest in Hispanics/Latinos and lowest in Black individuals across all age groups. ALL incidence is rising fastest in Hispanics/Latinos, in AYAs. In addition, survival is worse in Hispanic/Latino or Black ALL patients compared to those who are non-Hispanic White. Different molecular subtypes of ALL show heterogeneities in incidence rates and survival outcomes across age groups and race/ethnicity. Several ALL risk variants are associated genetic and demonstrate different risk allele frequencies and/or effect sizes across non-genetic socioeconomic to all influence the disparities in ALL risk and survival. Further studies are needed to investigate the potential joint effects and interactions of genetic and environmental risk factors. survival in Hispanic/Latino and Black patients with ALL advances in precision medicine approaches,","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43441983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B-cell receptor stereotyped subsets and outcome for patients with chronic lymphocytic leukemia in the HOVON 68 trial","authors":"F. Vojdeman, L. Pedersen, D. T. Raa, V. Juvonen, Y. Norden, G. Tjønnfjord, E. Kimby, M. Itälä-Remes, R. Rosenquist, A. Langerak, L. Evers, T. Zenz, J. Walewski, M. V. Oers, C. Geisler, A. Kater, C. Niemann","doi":"10.20517/jtgg.2021.03","DOIUrl":"https://doi.org/10.20517/jtgg.2021.03","url":null,"abstract":"Aim: We here assessed the impact of B-cell receptor stereotypy on progression-free survival (PFS) and overall survival in patients from the HOVON 68 trial. Methods: Based on IGHV mutational analyses from participating centers in Sweden, Norway, Finland, Denmark, Poland, and the Netherlands, B-cell receptor stereotyped subsets were assigned using the ARResT/AssignSubsets software. Analysis for recurrent mutations was performed by next-generation sequencing by a 454-base platform. All other clinical data were extracted from the HOVON database by November 2016. Results: In total, 178 out of 192 patients with sequences available were technically suitable for analysis. Thirty-eight patients (21%) were assigned to one of the 19 major subsets: Subset #2 ( n = 12, 6.7%), Subset #8 ( n = 7, 3.9%), Subset #6 ( n = 6, 3.4%), and Subset #1 ( n = 5, 2.8%). Other subsets found were: Subsets #3, #5, #31, and #64B. By November 2016, a PFS event had occurred for 150 patients (84%) and 79 patients (44%) had died. The median follow-up time for patients still alive was 78.9 months. Patients with UM-IGHV belonging to Subset #2 had significantly longer PFS than UM-IGHV 3-21-utilizing non-Subset #2 patients [UM-IGHV Subset #2 median PFS 61.3 months ( n = 8) vs. UM-IGHV 3-21 non-Subset #2 median PFS 22.3 months ( n = 6), P = 0.01]. Overall, no significant differences in PFS between groups were found for patients with M-IGHV. Conclusion: In the HOVON 68 trial. Subset #2 patients had a good treatment outcome comparable to the outcome for non-high-risk patients with chronic lymphocytic leukemia following fludarabine-cyclophosphamide-rituximab-based treatment.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49053624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An update of aberrant methylation detection on circulating cell-free DNA as a tool to improve prostate cancer diagnosis and prognosis","authors":"N. Pavan, G. Grassi, B. Scaggiante","doi":"10.20517/jtgg.2021.18","DOIUrl":"https://doi.org/10.20517/jtgg.2021.18","url":null,"abstract":"Prostate cancer (PCa) remains a disease of high incidence, but orphan of a specific screening program. For this reason, non-invasive techniques capable to predict PCa in patients with high specificity and sensitivity are still an urgent need. One of the major goals is to improve the PCa diagnosis and the identification of patients who benefit from tissue biopsies. Another need is the necessity to have novel biomarkers to better stratify the risk of patients with PCa to predict the aggressiveness of the tumor and the overall survival. Liquid biopsy can be an important non-invasive tool to stratify PCa at the molecular level to improve diagnosis and prognosis, and, possibly, to develop screening programs and follow-up. With this review, we are reporting the lastest update of aberrant methylation detection on circulating tumor DNA as a tool to improve prostate cancer diagnosis and prognosis.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47606685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-scale genomic data-mining implicates dysregulated nuclear receptor-mediated signaling in mental illness","authors":"Julie G. Donskov, A. Starnawska, Jonatan Pallesen, J. Grove, A. Børglum, P. Qvist","doi":"10.20517/jtgg.2021.12","DOIUrl":"https://doi.org/10.20517/jtgg.2021.12","url":null,"abstract":"Aim: Mental illness comprises a group of heterogeneous conditions attributable to a complex interplay between hereditary and environmental components. Acting at the interface between environmental stimuli and their genomic actions, nuclear receptors (NRs) appear uniquely suited to facilitate gene-environment interactions in the context of mental health. Genetic disruptions to the NR transcriptomic complex (NTC) give rise to neuropsychiatric pathologies, and epidemiological risks involving a steroid response are among the most replicated in psychiatry. Importantly, pharmacological targeting of NR-mediated signaling is clinically effective in the treatment of psychiatric disorders. Here, we systematically interrogated large-scale deposited data to provide a comprehensive evaluation of the genomic NTC risk burden in mental illness. Methods: Utilizing data from large, recent genome-, exome-, and methylome-wide association studies on psychiatric disorders, we assessed the representation of NTC genes among top associated loci and tested the gene set associations for NTC and NR target genes using GWAS summary statistics. Through data mining and transcriptomic profiling of NR-mediated signaling in the diseased and healthy human brain, we categorized psychiatry-relevant NTC gene networks. Results: We found that NTC genes are significantly overrepresented in genome-, methylome-, and exome-wide associated loci and that the NTC, as well as NR target gene sets, is overall associated with mental illness. Accordingly, we identified transcriptomic NTC signatures in patient brain samples. In line with a key role for orchestrated NR-mediated signaling in the developing brain, particularly NTC co-expression networks with prenatal peak expression are enriched with differentially methylated, sex-biased, and psychiatry-associated risk variants. Conclusion: Here, we provide multilevel evidence that supports genomic NR-mediated signaling as a common and core molecular mechanism in mental illness, and we highlight specific NR-signaling pathways with putative diagnostic and pharmacological intervention potential in psychiatry.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44880680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omics analyses provide insights to CART cell therapy resistance","authors":"Michelle J. Cox, S. Kenderian","doi":"10.20517/JTGG.2021.06","DOIUrl":"https://doi.org/10.20517/JTGG.2021.06","url":null,"abstract":"Chimeric antigen receptor T (CART) cell therapy has revolutionized the treatment of relapsed/refractory B cell malignancies in recent years. Despite high initial response rates, durable response rates are low, and CART cell efficacy in solid tumors is very modest. Additionally, the overall success of CART cell therapy is limited by toxicities such as cytokine release syndrome and neurotoxicity. Decades of advancement in genome sequencing technology and bioinformatics have given us a better understanding of how cancer develops and evolves following treatments. This has resulted in a better understanding of patient response to cancer treatment on a molecular level. Resistance to CART cell therapy can be mediated by the cancer cells, the tumor microenvironment, or the patient’s T cells. In this review, we will outline lessons learned from multi-omics studies (1) to identify biomarkers of response or toxicity to CART cell therapy or (2) to develop biomarker-guided therapeutic interventions to overcome these limitations.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46961730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenetics and pharmacogenomics in human diseases","authors":"R. Cacabelos","doi":"10.20517/JTGG.2021.07","DOIUrl":"https://doi.org/10.20517/JTGG.2021.07","url":null,"abstract":"© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.","PeriodicalId":73999,"journal":{"name":"Journal of translational genetics and genomics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45542050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}