3613 results for "*geneti*"

in 56.50 milliseconds.

• Whole Genome Sequencing Analysis of Adult T-cell Leukemia/Lymphoma

  In this study, we have performed the whole genome sequencing (WGS) for primary tumors from adult T-cell leukemia/lymphoma (ATL) to identify recurrent genetic mutations and structural variants.

  Study JGAS000320

• 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

• Identification of genetic polymorphism on aggressive periodontitis

  Periodontitis is an inflammatory disease with loss of gingival tissue and alveolar bone. Aggressive periodontitis is rapidly progressive form of periodontitis in young people. It has been demonstrated that the susceptibility to AgP is influenced by genetic risk factors. However few were established as a risk factor for aggressive periodontitis. To identify genetic risk factors for aggressive periodontitis in Japanese population, we conducted the exome sequence of unrelated patients.

  Study JGAS000040

• 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

• Development of cell lines and mouse models of bone and soft tissue sarcoma to establish novel treatment

  Malignant giant-cell tumors are extremely rare bone sarcomas that transform from conventional giant-cell tumors during long periods of treatment. We have applied the culture methods and succeeded in establishing patient-derived organoids (PDO) of rare sarcomas. This study aimed to investigate the genomic characteristics of our established novel organoids from human malignant giant-cell tumors. The developed tumors with xenograft were genomically analyzed to compare their characteristics with those of the original tumors. Genetic changes over time throughout treatment were analyzed, and the genomic status of the established organoid was confirmed. Next generation sequencing revealed that the established organoids lacked the H3-3A G34W mutation. The xenografted organoids of the malignant giant-cell tumor had phenotypes genetically similar to those of the original tumor. The established organoids were confirmed to be derived from human malignant giant-cell tumors. In summary, the present study demonstrated a novel organoid model of a malignant giant-cell tumor that was genetically confirmed to be a malignant transformed tumor. Our organoid model could be used to elucidate the molecular pathogenesis of a malignant giant-cell tumor and develop novel treatment modalities.

  Study JGAS000618

• 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

• Response to Hepatitis B vaccine

  Approximately 5-10% of individuals, who are vaccinated with a hepatitis B (HB) vaccine designed based on the HBV genotype C, fail to acquire protective levels of antibodies. Host genetic factors behind low immune response to the HB vaccine were investigated by GWAS and HLA association tests. GWAS and HLA association tests were carried out using a total of 1,193 Japanese individuals including 107 low responders (HBsAb ?10 mIU/mL), 351 intermediate responders (10 mIU/mL< HBsAb <100 mIU/mL), and 735 high responders (HBsAb ?100 mIU/mL). Classical HLA class II alleles were statistically imputed using the genome-wide SNP typing data. GWAS identified independent associations of HLA-DRB1-DQB1 haplotypes, HLA-DPB1 alleles and BTNL2 gene with immune response to the HB vaccine designed based on the HBV genotype C. Five HLA-DRB1-DQB1 haplotypes and two DPB1 alleles showed significant associations with response to the HB vaccine in a comparison of three groups of 1,193 HB vaccinated individuals. When frequencies of DRB1-DQB1 haplotypes and DPB1 alleles were compared between low immune responders and HBV patients, significant associations were identified for three DRB1-DQB1 haplotypes, and no association was identified for any of DPB1 alleles. In contrast, no association for DRB1-DQB1 haplotypes and DPB1 alleles was identified in a comparison between high immune responders and healthy individuals. The findings in this study clearly show the importance of HLA-DR-DQ (i.e. recognition of a HB vaccine related HBsAg by specific DR-DQ haplotypes) and BTNL2 molecules (i.e. high immune response to the HB vaccine) for response to a HB vaccine designed based on the HBV genotype C.

  Study JGAS000341

• Submission 48 - study_title 1

  Submission 48 - description 1

  Study EGAS50000000497

• Defining structural variation associated with breast cancer susceptibility by long-read genome sequencing

  Germline structural variants (SVs) are challenging to identify by conventional genetic testing assays. Long-read sequencing has improved the global characterization of SVs, but its sensitivity at genetic loci associated with high- and moderate-penetrance cancer susceptibility has not been reported. This study used long-read genome sequencing performed on the Oxford Nanopore Technologies' PromethION to resolve variants underlying breast cancer susceptibility in sixteen individuals with pathogenic germline SVs in BRCA1, BRCA2, CHEK2 or PALB2.

  Study EGAS50000000286

• Understanding_the_multicellular_dynamics_of_clear_cell_renal_cell_carcinoma___DNA_sequencing

  This study will reconstruct the single cellular phylogeny of tumour and immune cells in relation to both genomic, functional, and spatial location. 20 tumours in total will be studied, including non-progressing small renal masses, progressing small renal masses, relatively indolent larger tumours, and high risk tumour with metastatic sampling. We aim to: Generate a focused, comprehensive phylogenetic characterisation of tumour cells Understand the dependencies of the cancer genome, transcriptome, tissue architecture and the single cellular micro-environment Quantify the single cellular composition and functional intra- and inter- tumoural heterogeneity Determine the phylogeny of tumour associated lymphocytes and their relationship to neo-epitopes and the immune microenvironment Investigate the mechanisms by which the tumour-normal interface constrains tumoural growth

  Study EGAS00001003517

• MutWP4__CRUK_Grand_Challenge_Mutographs_of_Cancer__Pancreatic_Organoids

  The Mutographs project aims to advance our understanding of the causes of cancer through studies of mutational signatures. Led by Mike Stratton, together with Paul Brennan, Ludmil Alexandrov, Allan Balmain, David Phillips and Peter Campbell, this large-scale international research endeavour was awarded a Cancer Research UK Grand Challenge. Different patterns of somatic mutation are generated by the different environmental, lifestyle and genetic factors that cause cancer, many of them are still unknown. Within Mutographs, Kings College London will characterise the mutational signatures induced by putative human carcinogens in order to identify the origins of mutational signatures found in human cancers. To achieve this human organoid cell cultures will be exposed to a representative catalogue of known or suspected human carcinogens and mutagens and, using whole genome sequencing, the patterns of mutations induced by them will be determined. Somatic mutational signatures will be subsequently extracted by non-negative matrix factorisation methods and correlated with exposure data. Through an enhanced understanding of cancer aetiology, Mutographs unprecedented effort is anticipated to outline modifiable risk factors, lead to new approaches to prevent cancer, and provide opportunities to empower early detection, refine high-risk groups and contribute to further therapeutic development.

  Study EGAS00001003520

• MutWP5__CRUK_Mutographs_of_Cancer__BRCA_Carriers___WG__Novaseq_

  Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.

  Study EGAS00001003523

• The Genetic Analysis of multiple sclerosis

  We created these data in order to identify genetic variants associated with increased susceptibility to multiple sclerosis. Cases from many parts of the world were genotyped with the Illumina 660 chip along with Swedish controls. In our analysis we also used control data from the WTCCC2 common UK controls and from other published studies.

  Study EGAS00000000101

• MutWP5__CRUK_Mutographs_of_Cancer__BRCA_Carriers___Exome__Novaseq_

  Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.

  Study EGAS00001003526

• MutWP5__CRUK_Mutographs_of_Cancer__Cancer_Mastectomy__Exome__Novaseq_

  Cancer is a genetic disease caused by an accumulation of mutations, however many of these mutations have been identified in pathologically normal tissue. We aim to use laser-capture microscopy (LCM) to sample individual clones from breast tissue to identify whether cancer-associated mutations appear in this normal tissue, assess the mutational burden present, and identify the mutational processes causing these mutations. We will sample from a wide age range of individuals (&lt;20 to &gt;60 years old) to determine whether these processes differ in pre- and post-menopausal women. We will also be comparing the tissue from healthy individuals (samples from breast reduction surgery) to those at elevated risk of breast cancer (mastectomy from BRCA1/2 patients) and those who have breast cancer (adjacent normal, distal normal, and tumour tissue from mastectomy). This will allow us to determine how these processes are different between these groups of individuals, and gain insight into the earliest stages of tumor development.

  Study EGAS00001003528

• The Haemgen RBC study

  Anaemia is a major determinant of global ill-health. To refine our understanding of the genetic factors influencing red blood cell formation and function, we carried out a meta-analysis of genome-wide association studies (GWAS) for six red blood cell traits: haemoglobin (HB), mean cell haemoglobin (MCH), mean cell haemoglobin concentration (MCHC), mean cell volume (MCV), packed cell volume (PCV) and red blood cell count (RBC). We provide genome-wide association results for 62,553 people of European ancestry using up to 2,644,161 autosomal SNPs. Participants with extreme measurements (>+/-3SD from mean) were excluded on a per phenotype basis. Imputation was done using haplotypes from HapMap Phase 2. SNP associations with each phenotype were tested by linear regression using an additive genetic model. Associations were tested separately in each cohort, with principal components and other study specific factors as covariates to account of population substructure. We then carried out meta-analysis of results from the individual cohorts using z-scores weighted by square root of sample size. SNPs with MAF<1% (weighted average across cohorts) were removed, as were SNPs with weight <50% of phenotype sample size. Anaemia is a major determinant of global ill-health. To refine our understanding of the genetic factors influencing red blood cell formation and function, we carried out a meta-analysis of genome-wide association studies (GWAS) for six red blood cell traits: haemoglobin (HB), mean cell haemoglobin (MCH), mean cell haemoglobin concentration (MCHC), mean cell volume (MCV), packed cell volume (PCV) and red blood cell count (RBC). We provide genome-wide association results for 62,553 people of European ancestry using up to 2,644,161 autosomal SNPs. Participants with extreme measurements (>+/-3SD from mean) were excluded on a per phenotype basis. Imputation was done using haplotypes from HapMap Phase 2. SNP associations with each phenotype were tested by linear regression using an additive genetic model. Associations were tested separately in each cohort, with principal components and other study specific factors as covariates to account of population substructure. We then carried out meta-analysis of results from the individual cohorts using z-scores weighted by square root of sample size. SNPs with MAF<1% (weighted average across cohorts) were removed, as were SNPs with weight <50% of phenotype sample size.

  Study EGAS00000000132

• Identification of cis- and trans-regulatory variation modulating microRNA expression levels in human fibroblasts

  MicroRNAs (miRNAs) are regulatory noncoding RNAs that affect the production of a significant fraction of human mRNAs via post-transcriptional regulation. Interindividual variation of the miRNA expression levels is likely to influence the expression of miRNA target genes and may therefore contribute to phenotypic differences in humans, including susceptibility to common disorders. The extent to which miRNA levels are genetically controlled is largely unknown. In this report, we assayed the expression levels of miRNAs in primary fibroblasts from 180 European newborns of the GenCord project and performed association analysis to identify eQTLs (expression quantitative traits loci). We detected robust expression for 121 miRNAs out of 365 interrogated. We have identified significant cis- (10%) and trans- (11%) eQTLs. Furthermore, we detected one genomic locus (rs1522653) that influences the expression levels of five miRNAs, thus unraveling a novel mechanism for coregulation of miRNA expression

  Study EGAS00000000056

• HER2_positive_Breast_Cancer_

  We propose to definitively characterise the somatic genetics of HER2+ve breast cancer through generation of comprehensive catalogues of somatic mutations in a number of cases by high coverage genome sequencing coupled with integrated transcriptomic and methylation analyses.

  Study EGAS00001000042

• Osteosarcoma_Whole_Genome

  We propose to definitively characterise the somatic genetics of Osteosarcoma cancer through generation of comprehensive catalogues of somatic mutations by high coverage genome sequencing.

  Study EGAS00001000147

• Investigation of the genetic basis of the rare syndrome Post-Transfusion Purpura (PTP)

  The Post-Transfusion Pupura (PTP) syndrome although rare has severe side effects for 5-10 cases per annum in the UK as a result of transfusion. High quality DNA has been isolated from either whole blood or from cryopreserved mononuclear cells of 4 patients in order to study our postulation that the condition is caused by a loss-of-function mutation in a specific gene.

  Study EGAS00001000053

• The patterns and dynamics of genomic instability in metastatic pancreatic cancer

  Pancreatic cancer is an aggressive malignancy with a five-year mortality of 97–98%, usually due to widespread metastatic disease. Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations, but genomic rearrangements have not been characterized in detail. Despite the clinical importance of metastasis, there remain fundamental questions about the clonal structures of metastatic tumours, including phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites, and how the tumour disseminates. Here we harness advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2–M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection.

  Study EGAS00000000064

• Distinct genomic profile and specific targeted drug responses in adult cerebellar glioblastoma

  Only a few studies have reported the molecular characteristics of adult cerebellar glioblastoma (C-GBM), a subtype comprising 1% of glioblastoma cases located within the infratentorial brain region due to the rarity. By identifying genomic profiles from 19 adult C-GBM samples, we revealed the genetic intertumoral heterogeneity in C-GBM as well as distinct genomic characteristics from those of supratentorial glioblastomas (S-GBMs), emphasizing the need of individualized therapies for C-GBM patients.

  Study EGAS00001002517

• Lethal malformation syndrome

  Identification of the genetic basis of rare monogenic diseases can provide insights into disease mechanisms, biological pathways and potential therapeutic targets. Exome sequencing has proven to be a powerful, efficient strategy for the identification of the genes underlying rare Mendelian disorders. The genetic defect behind the lethal malformation syndrome under study is known in some cases and has proven useful in revealing the primary underlying defect. We have six typical unrelated families with no known mutation. The aim of this study is to identify the locus associated with this lethal malformation syndrome in these families using exome sequencing.

  Study EGAS00001000061

• Whole_genome_sequencing_in_a_multiplex_Crohn_s_disease_family

  In 2009 we identified a four-generation family with over 700 members and 41 affected with Crohn's disease (CD). At the time we sequenced the exome of 6 affected individuals but did not identify any coding variants which appear to explain the high prevalence of disease. Since then we have collected DNA from a large number of additional family members, genotyped linkage arrays on the entire family to refine genomic regions shared by identity by descent and genotyped affected and unaffected members at known CD risk loci identified by Genome Wide Association Studies (GWAS). These analyses have confirmed that a significant unexplained excess of disease remains after accounting for all known genetic factors, and that several regions of the genome are shared by a large fraction of affected individuals. We therefore perform whole genomes sequencing from 8 individuals which will allow us to impute the complete sequence of nearly all the members of the two largest and most severely affected branches of the family.

  Study EGAS00001000060

• CRLF2_sequencing_project_Exomes

  I hope to gain insight into novel genetic aberrations present in these patients that will highlight important pathways that are involved in this subtype of leukaemia. It would be interesting to see if the mutations and pathways that are activated are consistent between the patients, or differences are observed dependent upon whether the patient has the translocation or the PAR1 deletion. Of note is the high association with either numerical gains of chromosome X or numerical/structural abnormalities of chromosome 21 (Down syndrome, iAMP21) in patients with CRLF2 deregulation. I hope to find abnormalities linking chromosomes X and 21 to CRLF2 deregulation in BCP‐ALL. By including the three patients that are normal for CRLF2, but have consistent genetic abnormalities found in the experimental cohort, I expect to find genetic differences between these two groups that will help us to identify novel molecular targets specific to CRLF2 deregulation.

  Study EGAS00001000081