A comprehensive canine genetics resource including gene and variation annotation

 描述(由申请者提供)：狗正在成为治疗癌症、炎症、心血管和行为疾病等人类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作图特别有效。虽然基因组、基本注释和SNP目录自2004年以来一直可用，但改进的基因组资源将使人们能够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更全面的基因组注释以及来自狗遗传社区的广泛基因组数据来改进犬基因组资源，作为UCSC基因组浏览器上的跟踪数据中心。六只因其他医疗原因而被安乐死的狗，将分别捐赠30个组织用于RNA测序，11个原代细胞培养用于五种组蛋白抗体的RNA测序和芯片测序。还将获得样本，用于每只狗的全基因组测序。这将产生30个组织的广泛的转录组资源，以及狗的第一个全基因组调控元件目录。还将从已经为其他科学研究牺牲的胚胎中获得狗胚胎的RNA测序。RNA测序数据将与以前的人类和狗基因注释在定制的注释管道中结合起来，主要基于物种特定的信息来改进狗的基因注释。所有上述数据，以及新的基因注释和从狗遗传学社区收集的数据将被托管在博德研究所的UCSC基因组浏览器上，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增加狗作为生物医学模型的效用，并将加快狗的遗传学和由狗模型研究产生的翻译研究。这一重要项目的合作者包括塔夫茨兽医学校的兽医专家DRS Sharp和Ferrer、狗胚胎发育专家Meyers-Wallen博士、兰德博士和布罗德研究所基因组平台的测序专家、转录组和基因组调控专家DRS Regev和Grabherr以及UCSC基因组浏览器的领导者DRS Haussler和Kent。

 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.