Tools for Genetic and Genomic Studies in the Dog

狗的遗传和基因组研究工具

基本信息

批准号：
8005159
负责人：
GREGORY M ACLAND
金额：
$ 17.23万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-22 至 2011-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8005159
关键词：
8 year old Affect Aggressive behavior Anatomy Animal Hospitals Animal Model Animals Applications Grants Archives Bar Codes Behavior Bioinformatics Biology Biomedical Research Blood specimen Breeding California Canis familiaris Cataloging Catalogs Chromosome Mapping Clinical Collaborations Collection Communities Complex Computer Simulation Cost Sharing DNA Data Databases Development Diagnosis Disease Disease susceptibility Dog Diseases Dysplasia Ensure Fee-for-Service Plans Funding Future Gene Mutation Genes Genetic Genetic Heterogeneity Genetic Models Genetic Variation Genome Genomics Genotype Goals Grant Granulomatous Haplotypes Health Hepatic Hereditary Disease Hospitals Human Indium Individual Inherited Internet Mammals Maps Medical Medical Genetics Medicine Modeling Molecular Morphology Mus Pathologic Patients Phenotype Physiological Population Principal Investigator Process Qualifying Records Research Personnel Resources Retinitis Pigmentosa Review Committee Role Sampling Scientist Screening procedure Services Single Nucleotide Polymorphism Single Nucleotide Polymorphism Map Site Structure Surveys Ulcerative Colitis Universities University Hospitals Variant Visit Vocabulary base case control cost density disease diagnosis empowered genetic analysis genetic pedigree genome sequencing genome-wide human disease interest large bowel Crohn&apos s disease man programs repository research study tool trait

项目摘要

DESCRIPTION (provided by applicant): Recent developments in dog (Canis familiaris) genomics have catapulted this species to the status of a model organism, with major advantages for the study of complex genetic diseases and traits relevant to the human condition. Its rapid rise in genomics was fueled by a 7.6X genome sequence, the identification of over 2 million single nucleotide polymorphisms (SNPs), and a commercial SNP microarray with over 125,000 loci. These developments converge with the enormous phenotypic variation between different breeds, the recent establishment of many breeds by line breeding that has yielded an advantageous haplotype structure for genetic analyses, greater physiologic and anatomic relationship to human diseases than other animal models, and excellent pedigree records. The main barrier to fully exploit this model for genetic studies is ready access to sufficient numbers of control and affected animals relevant to the traits of interest. The Cornell University Hospital for Animals (CUHA) admits - 15,000 canine patients (5,000 new visits) each year. We propose to create a DNA repository from selected pure-breed dogs admitted to our hospital accurately diagnosed with complex diseases and traits of strong biomedical interest. A conservative estimate is that approximately 2,000 DNA samples per year will be added to our existing collection, and a subset of up to 400 cases and controls per year will be subjected to high-density SNP genotyping. Initially, we will map loci for owner-directed aggression, rod-cone dystrophy, hepatic microvascular dysplasia, and granulomatous (ulcerative) colitis in specific breeds of dog. We will prospectively accumulate phenotypic data for the same specific breed controls. A standard phenotype screen will be performed on dogs over 8 years of age belonging to the same breeds admitted with the 12 most frequently diagnosed diseases in our hospital. We will encourage the canine genetic mapping community to submit requests for SNP genotyping of their cases and controls, on a cost-sharing basis. The Cornell Medical Genetic Archive will purchase an equal number of mapping arrays as supported by this grant application. Future mapping studies will concentrate on complex diseases of dogs among those breeds most frequently admitted to our hospital under the advice of highly qualified, external consultants. The SNP genotypes and accompanying phenotypes will be uploaded to the University of California Santa Cruz (UCSC) Genome Bioinformatics mirror and ported to the original UCSC site. We will help alleviate the need for scientists to repetitively collect control samples and we will provide SNP genotypes to allow in silico analyses at minimum cost. By combining a large collection of well phenotyped samples with SNP genotypes, this resource will facilitate the genetic analysis of complex traits, make the canine model accessible to a wide cadre of scientists, and empower the dog as an indispensable element in biomedical research.

描述（由申请人提供）：狗（Canis familis）基因组学的最新发展使该物种升高到模型生物体的状态，在研究复杂遗传疾病和与人类状况相关的复杂遗传疾病和特征方面具有很大的优势。它的基因组学快速上升是由7.6倍基因组序列，超过200万个单核苷酸多态性（SNP）的鉴定以及具有超过125,000个基因座的商业SNP微阵列的鉴定。这些发展与不同品种之间的巨大表型变化融合，最近通过线育种建立了许多品种，这对遗传分析产生了有利的单倍型结构，与其他动物模型相比，与人类疾病更大的生理和解剖学关系以及出色的谱系记录。充分利用该模型进行遗传研究的主要障碍是准备获得足够数量的控制，并影响与感兴趣特征有关的动物。康奈尔大学动物医院（CUHA）每年接受15,000名犬类患者（5,000例新访问）。我们建议从准确诊断出患有复杂疾病和强烈生物医学感兴趣的特征的医院的选定纯种狗中创建一个DNA存储库。保守的估计是，每年将大约2,000个DNA样本添加到我们现有的收集中，并且最多400例病例和对照将进行高密度SNP基因分型。最初，我们将在特定狗的特定犬种中绘制基因座，以绘制所有人定向的攻击性，棒杆骨营养不良，肝微血管发育不良和肉芽肿性（溃疡性）结肠炎。我们将前瞻性地积累相同特定品种控制的表型数据。将对属于8岁以上的狗进行标准表型屏幕，该狗属于同一品种，该品种被我们医院的12种最常见的疾病所接受。我们将鼓励犬基因地图社区以成本分配的基础提交其病例和控制的SNP基因分型的请求。 Cornell Medical Genetic Archive将在此赠款应用程序的支持下购买相等数量的映射阵列。未来的映射研究将在高素质的外部顾问的建议下，将狗的复杂疾病集中在我们医院最常被送往我们医院的复杂疾病。 SNP基因型和随附的表型将上传到加利福尼亚大学圣克鲁斯分校（UCSC）基因组生物信息学镜像，并移植到原始的UCSC网站上。我们将帮助减轻科学家重复收集控制样本的需求，我们将提供SNP基因型以最低成本允许进行计算机分析。通过将大量良好表型样品与SNP基因型相结合，该资源将促进复杂性状的遗传分析，使宽阔的科学家可以使用犬种模型，并使狗作为生物医学研究中不可或缺的元素。