4015 results for "*geneti*"

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• Genetic analysis in an inherited cardiac arrhythmia

  To identify a causative gene for an inherited cardiac arrhythmia, exome sequence analysis was conducted in 6 patients and 5 controls.

  Study JGAS000041

• Epigenomic analysis of human androgenetic trophoblast stem cells derived from complete hydatidiform mole

  A complete hydatidiform mole (CHM) is an abnormal pregnancy caused by genetic fertilization disorders. The aim of this study is to establish human trophoblast stem (TS) cell lines from CHMs and elucidate their pathogenesis.

  Study JGAS000207

• DNA methylation array analysis of pediatric T-cell acute lymphoblastic leukemia

  Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is rare and its pathogenesis is poorly understood. To investigate epigenetic profiles of pediatric T-ALL, we performed DNA methylation array analysis in 79 cases of pediatric T-ALL.

  Study JGAS000138

• Discovery of genetic factors associated with thiopurine-induced severe adverse events

  Despite NUDT15 variants showing significant association with thiopurine-induced adverse events (AEs) in Asians, it remains unclear whether additional genetic variants should be tested to predict AEs. To clarify it, we performed a genome-wide association study to discover additional variants associated with thiopurine-induced severe AEs, alopecia and leukopenia. GWASs of these AEs were performed with 1221 Japanese patients with inflammatory bowel disease using population-optimized genotyping array and imputation.

  Study JGAS000661

• Identification of the genes associated with EGFR-mutant lung cancer

  To gain an insight into the genetic factors underlying the carcinogenesis of EGFR-mutant lung adenocarcinoma, we sequenced the exomes in peripheral-blood DNA from the patients.

  Study JGAS000129

• Inherited chromosomally-integrated human herpesvirus 6A/B (HHV-6A/B) genome sequences in the Japanese population

  The deposited sequences represent inherited chromosomally-integrated human herpesvirus 6 (iciHHV-6) genomes identified from 10 BioBank Japan (BBJ) subjects based on the analysis of the whole-genome sequencing (WGS) data. In brief, we re-aligned unmapped reads from the WGS to HHV-6A genome (Genbank accession number: KJ123690.1) using BWA-MEM algorithm. Ten out of 3,256 subjects were identified with high depth of coverage of HHV-6. We further distinguished subjects with integrated HHV-6A subtypes from those with integrated HHV-6B based on phylogenetic analysis of concatenated sequences of three viral genes (U27/U43/U83, which show high divergence between viral species). We reconstructed the HHV-6 viral genome of 10 subjects. First, reads that mapped to a reference HHV-6A genome (KJ123690.1) were further aligned against the integrated HHV-6A genome derived from a Japanese individual NA18999 (GenBank Accession number: KY316047.1) using BWA-MEM. Based on the alignment, variant calling was performed using freebayes (version: v1.2.0-2-g29c4002) with parameters ploidy = 1 and min-alternate-fraction = 0.8 {Garrison, 2012}. We generated subject-specific iciHHV-6 viral sequences by applying the resulting variants to the KY316047.1 reference genome using the FastaAlternateReferenceMaker function in the Genome Analysis Toolkit (GATK) v3.7. Please note that HHV-6B-specific variants are unlikely to be sensitively reconstructed using this method.

  Study JGAS000240

• Searching for rare/low frequency variants in rheumatoid arthritis by exome sequencing

  Rheumatoid arthritis (RA) is a multifactorial and systemic autoimmune disease and characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage and bone destruction and systemic features including cardiovascular, pulmonary, psychological and skeletal disorders. Although the causality of RA is not completely understood, genetic factors contribute to the onset. About 60% of the RA risk is genetic. To identify causative- or susceptible- rare/low-frequency variants in RA, exome sequencing of 39 patients with RA was conducted. We also conducted genotyping of pooled healthy men and women exome-sequencing data.

  Study JGAS000035

• High-coverage whole-genome sequencing reveals structural variations in triple-negative breast cancer

  Triple-negative breast cancer (TNBC) cells do not express estrogen receptors, progesterone receptors or human epidermal growth factor receptor 2 (HER2). Currently, apart from poly ADP-ribose polymerase (PARP) inhibitors, there are few effective therapeutic options for this cancer type. Here, we present a comprehensive characterization of genetic alterations in TNBC via high-coverage whole-genome sequencing along with transcriptomic and whole-exome sequencing. Silencing of BRCA1 gene impaired the homologous recombination (HR) pathway in a subset of TNBC, which exhibited similar phenotypes with tumors with BRCA1 mutations; they harbored many structural variations (SVs) with relative enrichment for tandem duplication. Clonal analysis suggested that TP53 mutations and methylation of CpG dinucleotides in the BRCA1 promoter were the early events of carcinogenesis. SVs were associated with driver oncogenic events such as amplification of MYC, NOTCH2 or NOTCH3 and impacted tumor suppressor genes including RB1, PTEN and KMT2C. We also identified a variety of oncogenes that could transform 3T3 mouse fibroblast cells, suggesting that individual TNBC tumors may undergo a unique driver event that can be targetable. Thus, we revealed several features of TNBC that had important clinical implications.

  Study JGAS000095

• Genetics of diffuse large B-cell lymphoma in Japan

  Diffuse large B-cell lymphoma (DLBCL) is a common hematological malignancy. Treatment with standard chemotherapy results in long-term remission in approximately 60% of patients. Whole-exome sequencing studies of large DLBCL cohorts revealed the biological diversity of tumors and facilitated the identification of genetic subtypes based on genetic alterations. Despite the progress facilitated by NGS, genetic classification is difficult to apply in clinical practice because of the complexity of the clustering algorithm. Furthermore, only a few reports included large Asian cohorts. Thus, a genetic overview of Japanese patients with DLBCL is still needed. Thus, in this study, we aimed to establish the clinical application of our simplified genetic classification algorithm in Japanese DLBCL.

  Study JGAS000307

• Next-generation sequencing-based comprehensive genetic analysis of undiagnosed disease

  The purpose of this study is to perform comprehensive genetic analysis using next-generation sequencers to make genetic diagnosis of "undiagnosed diseases".

  Study JGAS000522

• Mutational Spectrums and Clinical Features of Patients with LOXHD1 Variants Identified in a 8,074 Hearing Loss Patient Cohort.

  Variants of LOXHD1 gene, which are expressed in hair cells of the cochlea and vestibule, have been reported to cause a progressive form of autosomal recessive non-syndromic hereditary hearing loss, DFNB77. In this study, genetic screening was conducted on 8,074 Japanese hearing loss patients utilizing the massively parallel DNA sequencing, to identify individuals with LOXHD1 variants and to assess their phenotypes. 28 affected individuals and 21 LOXHD1 variants were identified, among which 13 were novel variants.

  Study JGAS000192

• Integrated multi-omics analysis of pediatric hepatoblastoma

  Hepatoblastoma (HBL) is the most common malignant liver tumor in childhood and is clinically heterogeneous. In spite of its heterogeneity, the molecular basis responsible for the difference between low-risk and high-risk HBL has not been fully clarified. To address this issue, we carried out multi-omics analysis on 59 HBL samples to generate comprehensive profiles of gene mutation, copy-number alteration, DNA methylation and gene expression. By integrating these data, we aimed to unravel the heterogeneity of HBL and identify genetic determinants and therapy targets of high-risk HBL.

  Study JGAS000188

• RNA-seq analysis of BMP-stimulated glioma initiating cells

  Bone morphogenetic protein (BMP) signaling has been shown to suppress progression of glioblastoma by promoting astrocytic differentiation; however, roles of BMP signaling in cell proliferation and apoptosis of glioblastoma cells remains to be elucidated. We here performed RNA-seq analysis of glioma initiating cells to identify transcriptional target(s) of BMP.

  Study JGAS000077

• Comprehensive genetic analysis of pediatric germ cell tumors

  Germ cell tumors (GCTs) are relatively rare tumors in children. Previous studies showed that adult testicular GCTs had some genomic alterations, but genetic basis of pediatric GCTs is still to be elucidated. We applied DNA methylation array analysis, whole-transcriptome sequencing, targeted capture sequencing, and SNP array analysis to fifty-one GCT samples.

  Study JGAS000204

• Genetic architecture of microRNA expression and its link to complex diseases in the Japanese population

  We mapped microRNA expression quantitative trait loci by quantifying microRNA expression using small RNA sequencing.

  Study JGAS000504

• Elucidation of male-specific genetic regulation through multi-layered omics analysis

  We performed single-cell RNA-sequencing of peripheral blood mononuclear cells from asthma patients and single-cell multiome (RNA+ATAC) profiling from COVID-19 patients.

  Study JGAS000862

• Impact of germline pathogenic variants in 27 cancer-predisposing genes on the risk of lymphoma

  The application of advanced molecular technology has significantly expanded lymphoma classification, allowing risk stratification and treatment optimization. Limited evidence suggests the presence of a genetic predisposition in lymphoma, indicating the potential for better individualized clinical management based on a novel lymphoma classification. Herein, we examined the impact of germline pathogenic variants in 27 cancer-predisposing genes with lymphoma risk and explored the clinical characteristics of pathogenic variant carriers. This study included 2,066 lymphoma patients and 38,153 cancer-free controls from the Japanese population. Following quality control of sequencing data, samples from 1,982 lymphoma patients and 37,592 controls were further analyzed. Sequencing data of controls were obtained from JGAD000721. Germline pathogenic variants in some cancer-predisposing genes were associated with a high risk of lymphoma. Furthermore, germline pathogenic variants in these genes were especially associated with the higher risk of a certain subtype. These results would provide novel insights concerning monogenic form into lymphoma classification. Some lymphoma patients may benefit from surveillance and targeted treatment like other neoplasms.

  Study JGAS000347

• Japanese Reference Genome JG1

  The complete human genome sequence is used as a reference for next-generation sequencing analyses. However, some ethnic ancestries are under-represented in the reference genome (e.g., GRCh37) due to its bias toward European and African ancestries. Here, we perform de novo assembly of three Japanese male genomes using >100�� Pacific Biosciences long reads and Bionano Genomics optical maps per sample. We integrate the genomes using the major allele for consensus and anchor the scaffolds using genetic and radiation hybrid maps to reconstruct each chromosome. The resulting genome sequence, JG1, is contiguous, accurate, and carries the major allele for a Japanese population.

  Study JGAS000259

• Whole-exome sequencing of MDS and related myeloid neoplasms

  Myelodysplastic syndromes(MDS) and related myeloid neoplasms (myelodysplasia) are heterogenous group of myeloid neoplasms characterized by deregulated blood cell production with evidence of myeloid dysplasia. Previously, frequent mutations in genes on RNA splicing machinery and DNA methylation pathway have been identified. However, comprehensive analysis of genetic alterations have not performed on a large cohort of these diseases. Therefore, in this study, we performed whole-exome sequencing of MDS and related myeloid neoplasms.

  Study JGAS000023

• Defined Lifestyle and Germline Factors Predispose Asian Populations to Gastric Cancer

  Gastric cancer (GC) is one of the leading causes of cancer mortality throughout the world, with the highest incidence in east-Asia. Although the somatic genetics of GC has extensively been characterized by recent advances in cancer genome sequencing, the germline and environmental effects on GC and their ethnic differences have poorly been understood. Here, we performed genomic scale trans-ethnic analysis of 531 GC cases (319 Asian and 212 non-Asians), by integrating east-Asian and public GC datasets. There is one distinct GC subclass with clear alcohol-associated mutation signature and strong Asian specificity, and almost all the cases in the subclass are attributable to alcohol intake behavior, smoking habit, and Asian-specific ALDH2 defective allele. Alcohol-related GCs have low mutation burden and a characteristic immune profile of increased B-cell infiltration into the tumor area in relation to cancer cell-intrinsic CXCL13 chemokine expression. In addition to germline variants of genes involved in BRCA pathways, we found frequent (7.4%) germline CDH1 variants among Japanese GCs. Most of them were attributed to a few recurrent SNVs shared by both Japanese and Koreans, suggesting the existence of common ancestral events and widespread distributions of these pathogenic variants among east-Asian populations. Specifically, approximately one-fifth of diffuse-type GCs were attributable to the combination of alcohol intake and defective-ALDH2 allele or to germline CDH1 variants. These results revealed uncharacterized impacts of germline variants and their interplays with lifestyles in the high incidence areas.

  Study JGAS000229

• Genetic and epigentic analysis of non-alcoholic fatty liver disease. Methylation analysis of nonalcoholic fatty liver.

  The aim of this study is to elucidate the mRNA expression related to the development and/or progression of non-alcoholic fatty liver disease. We performed genome-wide methylation analysis and determined the differentially methylated CpGs between mild and advanced nonalcoholic fatty liver disease.

  Study JGAS000059

• Research of factors related to diagnosis, progression, prognosis and treatment of hepato-biliary-pancreatic malignancies

  Advanced cancers with metastasis and/or recurrence are usually resistant and refractory to treatment. In our studies, whole exome sequencing analysis, comprehensive epigenetic analysis and genome-wide expression analysis were performed using cancerous and non-cancerous tissues derived from multicentric cohort study of hepatocellular carcinoma (HCC). The aim of the studies is identification of the refractoriness-related deriver genes for application to novel molecular targeted therapy and preventive medicine. The studies are intended for refractory HCC. High frequency of the tumor recurrence even after curative resection is one of the major difficulties in the treatment of HCC. According to our previous studies, not the recurrence itself, but the recurrence pattern has critical effects on prognosis of the patient with HCC. Then, we analyzed the cancerous and non-cancerous tissues of primary HCC on the point of the recurrence patterns in accordance with or without Milan criteria. The materials were obtained from thirty three patients underwent curative hepatectomy for HCC at Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University Hospital. Written informed consent from these patients, as well as the institutional review board approved was obtained. The determination of the refractory HCC group (16 cases) was based on the point of the recurrence patterns in accordance with Milan criteria for the recurrent tumor (solitary <5cm, or up to 3 nodules <3 cm, without major vascular invasion or distant metastasis) that has been proposed as the useful criteria of the liver transplantation for HCC. The cellular DNA was extracted from the cancerous and non-cancerous tissues of primary HCC by the phenol-chloroform method. After SNP certification using Genome-Wide Human SNP Array 6.0 (Affymetrix), whole exome sequencing was performed at the Cancer Institute of JFCR, as the support infrastructure. Exome sequencing was performed using HiSeq 2000 (Illumina), and the obtained reads were mapped to the human reference genome (hg19) using BWA software. GATK software was used for local realignment base call recalibration. Single nucleotide variants (SNVs) and indels were analyzed by MuTect and SomaticIndelDetector, as well as visual confirmation by IGV software.

  Study JGAS000052

• Target sequencing of 27 cancer-predisposing genes and 13 renal cell carcinoma-related genes in Japanese renal cell carcinoma patients

  Identifying causative genes via genetic testing is useful for the screening, prevention, and treatment of cancer. Several hereditary syndromes are known to occur in renal cell carcinoma (RCC). However, these evidences came from the European population; it remains unclear how the RCC-related genes and other cancer-predisposing genes contribute to the development RCC in the Japanese population. A case-control study of 14 RCC-related genes and 26 cancer-predisposing genes was performed using 1,563 Japanese patients with RCC and 6,016 controls. Patients were divided into two major histological subtypes of clear cell RCC (ccRCC) or non-clear cell RCC (nccRCC). Gene-based analysis of germline pathogenic variants in patients with each subtype and cancer-free subjects was performed. Following quality control, 1,532 patients with RCC and 5,996 controls were further analyzed. For ccRCC, 52 of 1,283 (4.05%) patients carried pathogenic variants mainly in the cancer-predisposing genes such as TP53 (P = 1.73 �� 10-4; OR, 5.8; 95% CI, 2.2���15.7). Approximately 80% of patients with pathogenic variants in TP53 had p.Ala189Val that was specific in East Asian population. For nccRCC, 14 of 249 (5.62%) patients carried pathogenic variants mainly in the RCC-related genes such as BAP1 (P = 6.27 �� 10-5; OR, Inf; 95% CI, 10.0���Inf), and FH (P = 6.27 �� 10-5; OR, Inf; 95% CI, 10.0���Inf). Our study showed different and population-specific contributions of risk genes between ccRCC and nccRCC in Japanese for better-personalized medicine.

  Study JGAS000414

• 3.5KJPNv2, an allele frequency panel of 3,552 Japanese individuals

  In the Tohoku Medical Megabank Project, we have conducted whole-genome sequencing of nearly 4,000 individuals from a Japanese population, and constructed an allele frequency panel of 3,552 individuals (3.5KJPNv2) after removing genetically related individuals. The 3.5KJPNv2 was constructed by using a standard pipeline including the 1KGP and gnomAD algorithms to reduce technical biases and to allow comparisons to other populations. The 3.5KJPNv2 includes variants in chromosome X and mitochondrial genome as well as autosome. The submitter has changed the access level of this study from controlled-access [Type I] to un-restricted access since 11th, January, 2019. The un-restricted access data ?hum0015.v3.3.5kjpnv2.v1? are available at the NBDC site: https://humandbs.biosciencedbc.jp/en/hum0015-v3. This study does not contain any controlled-access dataset.

  Study JGAS000159

• Genomic profiling identified ERCC2 helicase domain mutations respond to platinum-based neoadjuvant therapy in urothelial bladder cancer

  Genomic profiling of tumours enables therapeutic decisions, and identifying drug-matched mutations will prolong survival and prognosis. Here, we generated a custom panel for detecting genetic alterations in 19 patients with urothelial bladder cancer. This panel targeted 71 genes associated with urological cancer. Targeted sequencing was performed on formalin-fixed paraffin-embedded tumour tissues. In this study, we revealed genome profiles and actionable mutations in patients with urothelial bladder cancer.

  Study JGAS000241