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（由申请人提供）：迄今为止，人家庭和人群中疾病易感基因的鉴定一直集中在常染色体显性高度渗透基因的映射和克隆上，该基因通过使用极端“高风险家庭”的连锁映射研究确定。这样的家庭很少见，因为它们的规模较小，通常会提供有限的遗传信息，尤其是如果关键家庭成员已故或没有产生后代。此外，人类人群结构的固有局限性，例如长期的时间和超出繁殖意味着，弱渗透物的基因会产生可变的表型，或与其他基因共同起作用以产生复杂的表型，这是极难映射的。对于像癌症这样的疾病，尤其如此，其中众多低渗透剂等位基因在人群中占疾病的很大比例。我们以前假设家养犬比其他与人类疾病相关的映射基因提供了多个关键优势。明显的优势包括狗的家庭规模较大，创始人的效果和狭窄的人口瓶颈，这会导致纯种狗之间的常见疾病的基因座异质性有限。在这项拨款中，三个经验丰富的互动群体将扩大其持续的合作，以开发其在狗中的基础设施，从而在狗中建立其他犬类的疾病，从而使其他犬类的疾病成为众多的疾病，以使其成为众多的疾病，以使其成为友好的疾病，以使其成为友好的疾病，并将其与MAD稳定相同。以前，我们开发了由微卫星，EST和BAC末端组成的狗的综合1800标记减数分裂连接/辐射杂种（RH）图，该图占基因组95％以上。我们通过绘制几种疾病的基因座（包括犬肾癌和四种类型的视网膜变性）来证明这些地图的实用性。在此提案中，我们将为狗对这些疾病和其他感兴趣的疾病基因的位置克隆奠定阶段，1）从1倍犬基因组序列（TIGR）提供的1倍犬基因组序列（TIGR）中识别出10,000多个犬基因的碎片，适用于RH映射。 2）使用新开发的高分辨率（10,000-RAD）RH面板从10,000个犬基因中映射片段； 3）开发和使基因组学社区很容易获得犬类地图，其中包括当前未经生成的这些数据。

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