A High Density Gene Map of the Canine Genome

犬科动物基因组的高密度基因图谱

• 批准号: 6775573
• 负责人: BARBARA J. TRASK
• 金额: $ 55.47万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-15 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6775573
• 关键词: animal genetic material tag; biotechnology; computer assisted sequence analysis; cytogenetics; disease /disorder model; dogs; gene expression; genetic markers; genetic susceptibility; genome; genotype; linkage mapping; model design /development; molecular biology information system; molecular cloning; neoplasm /cancer genetics; nucleic acid sequence; oncogenes; polymerase chain reaction

DESCRIPTION (provided by applicant):The identification of disease susceptibility genes in human families and populations to date has focused on the mapping and cloning of autosomal dominant highly penetrant genes, identified by linkage mapping studies using extreme, "high risk families." Such families are rare and because of their small size often provide limited genetic information, particularly if key family members are deceased or have not produced offspring. In addition, inherent limitations in the structure of human populations, such as a long generation time and outbreeding mean that genes which are weakly penetrant, give rise to variable phenotypes, or act in concert with other genes to produce complex phenotypes are extremely difficult to map. This is particularly true for diseases like cancer, in which a multitude of low penetrant alleles are believed to account for a significant percentage of disease in the population.We hypothesized previously that the domestic dog offers several key advantages over other systems for mapping genes relevant to human disease. Obvious advantages include the large family size of dogs, as well as founder effects and narrow population bottlenecks that result in limited locus heterogeneity for common disorders among purebred dogs.In this grant, three experienced and interactive groups will expand their ongoing collaborations to develop the infrastructure for positional cloning in dogs, thus establishing the domestic dog as the model system of choice for mapping cancer susceptibility genes, as well as other common disease alleles. Previously we developed an integrated 1800 marker meiotic linkage/radiation hybrid (RH) map of the dog, composed of microsatellites, ESTs, and BAC-ends that spans over 95 percent of the genome. We have demonstrated the utility of these maps by mapping loci for several diseases, including canine renal cancer and four types of retinal degeneration. In this proposal we will set the stage for positional cloning of these and other disease genes of interest in the dog by 1) Identifying fragments from greater than 10,000 canine genes, suitable for RH mapping, from the 1x canine genome sequence being made available by The Institute for Genomic Research (TIGR); 2) Mapping fragments from 10,000 canine genes using a newly developed, high resolution (10,000-rad) RH panel; and 3) Developing and making readily available to the genomics community a canine RH map inclusive of these and additional data currently under generation.

描述（由申请方提供）：迄今为止，人类家族和人群中疾病易感基因的鉴定主要集中在常染色体显性高外显基因的定位和克隆上，这些基因是通过使用极端“高风险家族”进行的连锁定位研究确定的。“这样的家庭很少见，由于他们的规模小，往往提供有限的遗传信息，特别是如果关键的家庭成员死亡或没有产生后代。此外，人类种群结构的固有局限性，如世代时间长和远系繁殖，意味着弱外显、产生可变表型或与其他基因协同作用产生复杂表型的基因极难作图。这对于癌症等疾病尤其如此，在癌症中，许多低渗透等位基因被认为是占人口中疾病的显着百分比。我们以前假设，家犬提供了几个关键的优势，比其他系统定位与人类疾病相关的基因。明显的优势包括狗的大家庭规模，以及创始人效应和狭窄的人口瓶颈，导致纯种狗中常见疾病的基因座异质性有限。在这项资助中，三个经验丰富和互动的小组将扩大他们正在进行的合作，以开发狗的定位克隆基础设施，从而建立家犬作为定位癌症易感基因的首选模型系统，以及其他常见疾病的等位基因。以前，我们开发了一个集成的1800标记减数分裂连锁/辐射杂种（RH）的狗，微卫星，EST，BAC末端组成的地图，跨越95%以上的基因组。我们已经证明了这些地图的实用性映射位点的几种疾病，包括犬肾癌和四种类型的视网膜变性。在本提案中，我们将通过以下步骤为狗中这些和其他感兴趣的疾病基因的定位克隆奠定基础：1）从基因组研究所（TIGR）提供的1x犬基因组序列中鉴定来自超过10，000个犬基因的片段，这些片段适合于RH作图; 2）使用新开发的高分辨率的基因芯片，（10，000拉德）RH板;以及3）开发并向基因组学界提供包括这些和目前正在生成的额外数据的犬RH图。

项目成果

CRH_Server: an online comparative and radiation hybrid mapping server for the canine genome.

CRH_Server：犬基因组在线比较和辐射混合绘图服务器。

• DOI: 10.1093/bioinformatics/bth411
• 发表时间: 2004
• 期刊: Bioinformatics (Oxford, England)
• 作者: Hitte,Christophe;Derrien,Thomas;Andre,Catherine;Ostrander,ElaineA;Galibert,Francis
• 通讯作者: Galibert,Francis

Construction and characterization of a high-resolution, 9000-rad canine radiation hybrid panel.

高分辨率 9000 拉德犬辐射混合面板的构建和表征。

• DOI: 10.1111/j.1365-2052.2006.01513.x
• 发表时间: 2006
• 期刊: Animal genetics
• 影响因子: 2.4
• 作者: Senger,F;Cadieu,E;Evanno,G;Hitte,C;Berkova,N;Priat,C;Andre,C;Galibert,F
• 通讯作者: Galibert,F

An integrated 4249 marker FISH/RH map of the canine genome.

• DOI: 10.1186/1471-2164-5-65
• 发表时间: 2004-09-13
• 期刊: BMC genomics
• 影响因子: 4.4
• 作者: Breen M;Hitte C;Lorentzen TD;Thomas R;Cadieu E;Sabacan L;Scott A;Evanno G;Parker HG;Kirkness EF;Hudson R;Guyon R;Mahairas GG;Gelfenbeyn B;Fraser CM;André C;Galibert F;Ostrander EA
• 通讯作者: Ostrander EA