A comprehensive canine genetics resource including gene and variation annotation

全面的犬类遗传资源，包括基因和变异注释

• 批准号: 9128056
• 负责人: Elinor Karlsson
• 金额: $ 64.79万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-17 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9128056
• 关键词: Adult; Age; Antibodies; Area; Behavioral; Breeding; Canis familiaris; Cardiovascular Diseases; Cardiovascular system; Cataloging; Catalogs; Cell Line; Cells; ChIP-seq; Chromosome Mapping; Clinical Trials; Code; Communities; Complex; Coupling; Custom; Data; Data Display; Data Set; Disease; Dog Diseases; Drug or chemical Tissue Distribution; Embryo; Embryonic Development; Enhancers; Gene Expression Regulation; Genes; Genetic; Genetic Research; Genetic Transcription; Genome; Genomics; Goals; Health; Hereditary Disease; Histones; Human; Human Genetics; Human Genome; Inflammatory; Institutes; Lifting; Linkage Disequilibrium; Longevity; Malignant Neoplasms; Maps; Medical; Modeling; Mutation; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Disease; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Mental Health; Neurologic; Organ; Pathway interactions; Primary Cell Cultures; Production; Protein Isoforms; Proteins; Protocols documentation; Publishing; Regulation; Regulatory Element; Research; Resources; Sampling; Scientist; Signal Transduction; Specialist; Structure; Tissues; Transcript; Translating; Translational Research; Translations; United States National Institutes of Health; Untranslated RNA; Variant; Veterinary Schools; base; cell type; comparative; dog genome; epigenomics; genetic association; genetic resource; genetic risk factor; genome annotation; genome browser; genome sequencing; genome wide association study; genome-wide; genomic data; genomic platform; genomic variation; human disease; improved; member; novel; promoter; sex; trait; transcriptome; transcriptome sequencing; transcriptomics; treatment strategy; whole genome

 DESCRIPTION (provided by applicant): The dog is becoming an increasingly important biomedical model for human diseases such as cancer, inflammatory, cardiovascular and behavioural diseases. The unique breed structure makes trait mapping particularly efficient. While a genome, basic annotation and SNP catalog have been available since 2004, improved genomic resources would allow a more efficient identification of disease genes, pathways and mutations. In this project we aim to improve the canine genomic resources by creating a more comprehensive genome annotation along with extensive genomic data from the dog genetic community as a track data hub on the UCSC Genome Browser. Six dogs, euthanized for other medical reasons, will donate 30 tissues each for RNA- sequencing and 11 primary cell cultures for both RNA-sequencing and ChIP-sequencing for five histone antibodies. A sample will also be obtained for whole genome sequencing of each dog. This will yield an extensive transcriptome resource for 30 tissues and the first genome-wide catalog of regulatory elements in the dog. Embryonic dog tissue will also be obtained for RNA- sequencing from embryos already sacrificed for other scientific studies.The RNA-sequencing data will be combined with previous human and dog gene annotations in a custom annotation pipeline, to result in an improved dog gene annotation, based largely on species-specific information. All of the above data, along with the new gene annotation and data gathered from the dog genetics community will be hosted at the Broad Institute on the UCSC Genome Browser, enabling access to these resources by dog scientists around the world. These genomic resources will vastly increase the utility of the dog as a biomedical model and will accelerate dog genetics, and translational research arising from the study of the dog model. Collaborators for this important project include Drs Sharp and Ferrer, veterinary specialists at Tufts Veterinary School, Dr. Meyers-Wallen, an expert in dog embryonic development, Dr Lander and the Broad Institute Genomics Platform, experts in sequencing, Drs Regev and Grabherr, experts at transcriptomics and genome regulation and Drs Haussler and Kent, leaders of the UCSC genome browser.

 描述（由申请人提供）：狗正在成为人类疾病（如癌症、炎症、心血管和行为疾病）的越来越重要的生物医学模型。独特的品种结构使性状定位特别有效。虽然自2004年以来已经有了基因组、基本注释和SNP目录，但改进的基因组资源将允许更有效地识别疾病基因、途径和突变。在这个项目中，我们的目标是通过创建一个更全面的基因组注释沿着广泛的基因组数据从狗遗传社区作为一个跟踪数据中心的UCSC基因组浏览器，以改善犬基因组资源。由于其他医学原因而被安乐死的6只犬将捐献30个组织用于RNA测序，并捐献11个原代细胞培养物用于5种组蛋白抗体的RNA测序和ChIP测序。还将获得每只犬的全基因组测序样本。这将产生一个广泛的转录组资源的30个组织和第一个全基因组目录的调控元件在狗。从其他科学研究中已经牺牲的胚胎中获得的狗胚胎组织也将用于RNA测序。RNA测序数据将与以前的人类和狗基因注释在自定义注释管道中结合，以产生改进的狗基因注释，主要基于物种特异性信息。所有上述数据，连同新的基因注释和从狗遗传学社区收集的数据，沿着将托管在UCSC基因组浏览器上的布罗德研究所，使世界各地的狗科学家能够访问这些资源。这些基因组资源将极大地提高狗作为生物医学模型的实用性，并将加速狗遗传学和狗模型研究产生的转化研究。这一重要项目的合作者包括塔夫茨兽医学院的兽医专家Drs Sharp和Ferrer，狗胚胎发育专家Meyers-Wallen博士，测序专家Lander博士和Broad Institute Genomics Platform，转录组学和基因组调控专家Drs Regev和Grabherr以及UCSC基因组浏览器领导人Drs Haussler和肯特。