Laboratory of Translational Genomics

转化基因组学实验室

• 批准号: 9339178
• 负责人: MICHAEL DEAN
• 金额: $ 614.56万
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9339178
• 关键词: Adult; Bioinformatics; Biological; Biology; Bladder; Cancer Etiology; Cancer Patient; Candidate Disease Gene; Carcinogenesis Mechanism; Childhood; Collaborations; DNA; Data; Databases; Development; Disease; Emerging Technologies; Epidemiologic Studies; Family; Genetic; Genetic Markers; Genetic Variation; Genome; Genomics; Genotype; Germ Lines; Goals; Health; High-Throughput Nucleotide Sequencing; Inherited; International; Investigation; Investments; Laboratories; Laboratory Research; Laboratory Study; Lung; Malignant Neoplasms; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Maps; Meta-Analysis; Mission; Molecular Evolution; Outcome; Pathway interactions; Play; Population Genetics; Population Heterogeneity; Predisposition; Research; Research Personnel; Risk Factors; Role; Scanning; Sequence Analysis; Series; Signal Transduction; Single Nucleotide Polymorphism; Susceptibility Gene; Technology; Validation; Variant; Work; base; cancer epidemiology; cancer genetics; cancer genomics; cancer risk; cancer survival; cohort; deep sequencing; density; design; follow-up; gene environment interaction; genetic analysis; genetic epidemiology; genetic linkage analysis; genetic variant; genome wide association study; high risk; insight; interdisciplinary approach; international partnership; laboratory facility; malignant breast neoplasm; methylation pattern; novel; programs; tool; trait; validation studies

The Laboratory of Translational Genomics (LTG) conducts studies on germline and somatic genetics of cancer and analyses on particular regions of the genome conclusively identified in cancer-specific genome-wide association studies (GWAS) and linkage studies in high-risk families.Research Mission LTG's mission is to understand the contribution of germline and somatic genetic variation to cancer etiology and outcomes. Its primary goals are to investigate regions of genetic variation by:Detecting cancer susceptibility alleles Fine mapping of susceptibility alleles using sequence analysis and imputation from public databases Prioritizing variants for follow-up studies through bioinformatic analysis of candidate variants Deciphering the biological mechanisms underlying susceptibility alleles through laboratory investigationThe Laboratory of Translational Genomics (LTG) investigates the biological basis of common inherited genetic variants associated with cancer susceptibility. Together with NCI's Cancer Genomics Research Laboratory (CGR), formerly known as the Core Genotyping Facility (CGF), the Laboratory carries out genome-wide association studies (GWAS), including the project known as CGEMS (see below).Using data from large-scale GWAS that evaluate hundreds of thousands of single nucleotide polymorphisms (SNPs), investigators at the LTG are studying the associations between genetic markers and cancer risk. To understand the biology underlying these associations, investigators are following up with focused validation studies, deep-sequencing, and functional analyses, such as analyses of expression levels and methylation patterns. This research relies on multidisciplinary approaches from population genetics, epidemiology and molecular evolution.The Laboratory has a series of international collaborations collecting cancer patient material and data for pediatric and adult cancers.The Laboratory works closely with the NCI's CGR. CGR designs and conducts high throughput sequencing and genotyping in support of large-scale epidemiologic studies within the Division of Cancer Epidemiology and Genetics. CGR is also involved in the development of powerful bioinformatics tools that handle high volume genotype data generated from GWAS.Genome-Wide Association Studies GWAS have yielded close to 750 regions in the genome associated with 135 different diseases and traits. Of these, 135 regions are associated with nearly two dozen cancers, and six regions are associated with multiple cancers. To more fully understand these novel findings, laboratory studies at the LTG are underway to identify the causal variants responsible for these associations through validation, deep sequencing, and translational work. In doing so, researchers are providing functional and biological insights into the mechanisms of carcinogenesis.These efforts would not be possible without NCIs long term investment in the Cohort Consortium, an international partnership of four million people from 41 cohorts, comprised of diverse populations. The cohorts provide extensive risk factor data and biospecimens, including germline DNA.Cancer Genetic Markers of SusceptibilityCancer Genetic Markers of Susceptibility (CGEMS) is a collaborative project employing GWAS technologies to investigate several types of cancer, risk factors, and outcomes such as cancer survival.Recently, the Laboratory has focused on a series of follow-up studies from CGEMS prostate and breast cancer scans. Investigators at the LTG have mapped those common and uncommon genetic variants in order to nominate suitable variants for further functional studies. The LTG is also conducting genetic analyses for other malignancies, including cancer of the pancreas, bladder and lung.Partnerships and CollaborationsCollaborations and partnerships play a pivotal role in the next wave of genome-wide association studies. Data pooling has become essential in order to achieve the statistical power necessary to detect associations between genomic variants and a variety of health outcomes. High-density chips and emerging technologies now allow the genotyping of millions of SNPs across the genome. Partnerships between the LTG and numerous NCI grantee research organizations are underway , allowing investigation into carcinogenic pathways and gene-environment interactions.

转化基因组学实验室（LTG）对癌症的种系和体细胞遗传学进行了研究，并对在癌症特异性基因组特异性基因组关联研究（GWAS）中最终确定的基因组的特定区域进行了分析。 Its primary goals are to investigate regions of genetic variation by:Detecting cancer susceptibility alleles Fine mapping of susceptibility alleles using sequence analysis and imputation from public databases Prioritizing variants for follow-up studies through bioinformatic analysis of candidate variants Deciphering the biological mechanisms underlying susceptibility alleles through laboratory investigationThe Laboratory of Translational Genomics (LTG) investigates the biological basis of common inherited与癌症敏感性相关的遗传变异。与NCI的癌症基因组学研究实验室（CGR）一起，以前称为核心基因分型设施（CGF），实验室进行了全基因组关联研究（GWAS），包括称为CGEM的项目（请参阅下文）。使用大型GWAS的数据研究，该数据评估了数以千计的单核苷元素（Snpsiatiation）（Snpsiatiation）（Snpsiatiatiation）（Snpsiatiation）（SNPERIDER Polymorgs）（Snpsiatiatiation）（Snpsiatiatiation）（遗传标记和癌症风险。为了了解这些关联的生物学，研究人员正在跟进重点验证研究，深入序列和功能分析，例如表达水平和甲基化模式的分析。这项研究依赖于人群遗传学，流行病学和分子进化的多学科方法。实验室有一系列国际合作，收集了儿科和成人癌症的癌症患者材料和数据。实验室与NCI的CGR紧密合作。 CGR设计并进行高通量测序和基因分型，以支持癌症流行病学和遗传学分裂内大规模流行病学研究。 CGR还参与了强大的生物信息学工具的开发，这些工具处理由GWAS产生的大量基因型数据。GENOME范围的关联研究GWAS在基因组中产生了与135种不同的疾病和特征相关的基因组中的750个区域。其中，有135个区域与近二十个癌症有关，六个区域与多种癌症有关。为了更充分了解这些新颖的发现，LTG的实验室研究正在进行中，以通过验证，深入测序和翻译工作来确定负责这些关联的因果变异。在此过程中，研究人员正在为癌变机制提供功能和生物学见解。如果没有NCIS的长期投资，这是不可能的，这是由41个人群组成的41人组成的400万人的国际合作伙伴，由不同的人群组成。 The cohorts provide extensive risk factor data and biospecimens, including germline DNA.Cancer Genetic Markers of SusceptibilityCancer Genetic Markers of Susceptibility (CGEMS) is a collaborative project employing GWAS technologies to investigate several types of cancer, risk factors, and outcomes such as cancer survival.Recently, the Laboratory has focused on a series of follow-up studies from CGEMS prostate and breast cancer scans. LTG的研究人员绘制了这些常见和不常见的遗传变异，以提名合适的变体进行进一步的功能研究。 LTG还正在进行其他恶性肿瘤的遗传分析，包括胰腺癌，膀胱和肺癌。在下一波基因组全基因组协会研究的下一波中，PARTHERSENS和合作伙伴关系和合作伙伴关系和合作伙伴关系起着关键作用。为了实现检测基因组变异与各种健康结果之间关联所必需的统计能力，数据汇集已成为必不可少的。现在，高密度芯片和新兴技术允许在整个基因组上进行数百万个SNP的基因分型。 LTG与众多NCI受赠人研究组织之间的伙伴关系正在进行中，从而调查了致癌途径和基因环境相互作用。