The Development of the Domestic cat, Felis catus, as an

家猫（Felis catus）的发展

• 批准号: 6558902
• 负责人: STEPHEN J O'BRIEN
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6558902
• 关键词: animal genetic material tag; animal population genetics; biochemical evolution; cats; genetic disorder; genetic markers; genetic models; genetic polymorphism; genetic susceptibility; genome; linkage mapping; model design /development; nucleic acid repetitive sequence; nucleic acid sequence; polymerase chain reaction; species difference

A goal of our research is to characterize genetic organization in the domestic cat and to develop genomic resources facilitating and establishing Felis catus as a useful animal model contributing to our understanding of human hereditary disease analogues, neoplasia, genetic factors associated with host response to infectious disease and mammalian genome evolution. In order to map and characterize genes associated with inherited pathologies in the domestic cat which mirror inherited human conditions we have recently completed a second generation linkage map of integrated microsatellite (Type II) and Type I (coding genes) in the domestic cat. The map was generated in a 134-member, multi-generation backcross pedigree between the domestic cat and the Asian leopard cat (Prionailurus bengalensis) and consists of 334 markers including 81 Type I loci and 253 Type II loci (246 autosomal and 7 X-linked microsatellites. The average intragroup inter-marker distance of 11 centimorgans (cM) was observed over the 18 feline autosomes and the X chromosome. In order to increase marker density for greater genetic linking mapping resolution in disease pedigrees, we have isolated an additional 700 dinucleotide repeat loci from a (dCA.dGT) enriched library. Primers for amplification have been designed and tested for both product performance and locus heterozygosity in a panel of outbred domestic cats. The loci are currently being genotyped in a cat x rodent radiation hybrid panel, recently used in construction of a Type I/Type II radiation hybrid map (see ZO1 BC 10265-05 LGD). A highly efficient approach is being utilized with amplifications performed in 384-well format and traditional gel-based assays have been replaced by a homogeneous 5'-nuclease assay involving a single common probe for all genetic markers. Following genotyping, the markers will be integrated with the current radiation hybrid map of the cat, including 421 Type I and 265 Type II markers. Microsatellites mapped at regular physical intervals will be genotyped and mapped in a large multi-generation domestic cat pedigree to generate a genetic linkage map with full genome coverage of Felis catus and of sufficient resolution for linkage mapping in disease pedigrees.

我们研究的目标是描述家猫的遗传组织特征，并开发基因组资源，促进和建立猫科动物作为有用的动物模型，有助于我们了解人类遗传性疾病类似物、肿瘤、与宿主对传染病反应相关的遗传因素和哺乳动物基因组进化。为了绘制和表征与反映人类遗传状况的家猫遗传病理相关的基因，我们最近完成了家猫集成微卫星（II 型）和 I 型（编码基因）的第二代连锁图谱。 该图谱是在家猫和亚洲豹猫（Prionailurus bengalensis）之间的 134 个成员的多代回交谱系中生成的，由 334 个标记组成，包括 81 个 I 型基因座和 253 个 II 型基因座（246 个常染色体基因座和 7 个 X-基因座）。 18 年间观察到的平均组内标记间距离为 11 厘摩 (cM)。为了增加标记密度以提高疾病谱系中的遗传连锁图谱分辨率，我们从 (dCA.dGT) 富集文库中分离出额外的 700 个二核苷酸重复基因座，并设计并测试了用于扩增的引物。目前正在猫 x 啮齿动物辐射杂交组中对基因座进行基因分型，该组最近用于构建 I 型/Type。 II 辐射混合图谱（参见 ZO1 BC 10265-05 LGD）正在使用一种高效的方法，以 384 孔格式进行扩增，并且传统的基于凝胶的测定已被涉及单一常见的同质 5'-核酸酶测定所取代。探针所有的遗传标记。基因分型后，标记将与猫当前的辐射混合图谱整合，包括 421 个 I 型标记和 265 个 II 型标记。以规则的物理间隔绘制的微卫星将在大型多代家猫谱系中进行基因分型和绘制，以生成具有猫科动物全基因组覆盖的遗传连锁图谱，并且具有足够的分辨率用于疾病谱系中的连锁图谱。