The Rabbit Genome, Immune System and Ig Genetics

兔基因组、免疫系统和 Ig 遗传学

• 批准号: 7732415
• 负责人: rose G. mage
• 金额: $ 16.7万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 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/7732415
• 关键词: Animal Model; Animals; Antibodies; Archives; Autoimmune Diseases; Biotechnology; Breeding; CSNK1A1 gene; Communicable Diseases; Computer Systems Development; Databases; Depth; Development; Diagnostic; Educational workshop; Extramural Activities; Future; Genes; Genetic; Genetic Polymorphism; Genome; Human; Humoral Immunities; IGH@ gene cluster; Immune system; Immunoglobulin Allotypes; Immunology; Individual; Infectious Disease Immunology; Institutes; Laboratories; Modeling; National Institute of Allergy and Infectious Disease; Oryctolagus cuniculus; Paper; RNA Splicing; Recombinants; Recommendation; Records; Research Personnel; Resources; Site; Source; Study models; Support Contracts; Therapeutic antibodies; United States National Institutes of Health; animal breeding; genetic resource; genome sequencing; human disease; interest; mutant; programs; vaccine development; variable region gene

Rabbits are the only or best animal model for several infectious diseases. The sequence of the rabbit genome is currently unfinished at 2x, but deeper 7x coverage started in 2007. A 2006 NHGRI recommendation that rabbit be sequenced more deeply, describes the NIAID allotype-defined rabbits as a valuable resource for future SNP discovery. They have polymorphisms of a variety of immune system genes including allelic allotypes of the VH, CH, and CL regions of antibody molecules. The colony also contained descendants of rabbits formerly at the Basel Institute for Immunology, including mutant and wild-type parental of VH1a2-deleted Alicia, CK1 splicing defective Basilea, and several VH-CH recombinant heavy chain types. These rabbits were made available to interested individuals, particularly to sites where breeding colonies could be established. A 4D relational database contains more than 45 years of breeding records and other information about animals in the colony. The mutant ali animals have a deletion of a key variable region gene in the immunoglobulin heavy chain locus that is present in related 2R1 wild type rabbits. The mutants may be more susceptibe to infectious disease because they have abnormal delayed development of humoral immunity. In part as the result of a White Paper I coauthored in 2005 proposing deep sequencing of the rabbit genome, 7x coverage was completed In July 2008 at Broad Institute MIT and Harvard. Assembly of the deep coverage is anticipated in early 2009. The sequences we have been able to find and use in the incomplete 2x trace archive, and in the 7x trace archive have already proven useful for various studies. As a result of my efforts, two websites are now available one maintained by the National Center for Biotechnology Information (NCBI) http://www.ncbi.nlm.nih.gov/projects/genome/guide/rabbit/ -- and one by NIAID on Rabbit in Immunology & Infectious Disease (http://www3.niaid.nih.gov/research/resources/ri/. The latter site offers a summary of an NIAID workshop on Rabbit Models of Human Infectious diseases held in 2005 that I helped the extramural NIAID DMID to program and chair.

兔子是多种传染病的唯一或最佳动物模型。兔子基因组的序列目前未完成为2倍，但更深的7倍覆盖范围始于2007年。2006年NHGRI建议将兔子进行更深入的测序，描述了NIAID同种型定义的兔子是对未来SNP发现的宝贵资源。它们具有多种免疫系统基因的多态性，包括抗体分子的VH，CH和CL区域的等位基因同型。 该殖民地还包含前巴塞尔免疫学研究所的兔子的后代，包括VH1A2删除的Alicia的突变体和野生型亲代，CK1剪接有缺陷的Basilea和几种VH-CH重组重组链链类型。这些兔子可用于有兴趣的人，特别是可以建立繁殖菌落的地点。 4D关系数据库包含45年以上的繁殖记录和有关殖民地动物的其他信息。突变的ALI动物在免疫球蛋白重链基因座中具有关键变量区域基因的缺失，后者存在于相关的2R1野生型兔中。突变体可能对传染病更具感官，因为它们具有异常的体液免疫发育。在2005年我合着的一份白皮书的结果是，我提出了对兔子基因组进行深入测序的结果，2008年7月在Broad Institute MIT和哈佛大学完成了7倍的覆盖范围。预计将在2009年初进行深层覆盖范围。我们能够在不完整的2X跟踪档案中找到和使用的序列，在7x Trace Archive中，已经证明对各种研究有用。由于我的努力，现在可以使用两个网站，该网站由国家生物技术信息中心（NCBI）http://www.ncbi.nlm.nih.gov/project/projects/genome/genome/guide/rabbit/--和一个由Niaid在免疫学和感染性疾病中的NIAID上的网站。 （http://www3.niaid.nih.gov/research/resources/ri/。后一个网站提供了关于2005年人类传染病兔子模型的NIAID研讨会的摘要，我在2005年举行了我帮助外观的NIAID DMID dmid dmid dmid dmid dmid to program and Chair。

项目成果

Elvin A. Kabat (1914-2000).

埃尔文·卡巴特 (1914-2000)。

• DOI: 10.1038/35030291
• 发表时间: 2000
• 期刊: Nature
• 影响因子: 64.8
• 作者: Paul,WE;Mage,RG
• 通讯作者: Mage,RG

Distinct clonal Ig diversification patterns in young appendix compared to antigen-specific splenic clones.

与抗原特异性脾克隆相比，年轻阑尾中独特的克隆 Ig 多样化模式。

• DOI: 10.4049/jimmunol.168.11.5424
• 发表时间: 2002
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Sehgal,Devinder;Obiakor,Harold;Mage,RoseG
• 通讯作者: Mage,RoseG

Demonstration that mast cells, T cells, and B cells bearing the activating kit mutation D816V occur in clusters within the marrow of patients with mastocytosis.

证明携带激活套件突变 D816V 的肥大细胞、T 细胞和 B 细胞在肥大细胞增多症患者的骨髓内成簇出现。

• DOI: 10.1016/s1525-1578(10)60529-6
• 发表时间: 2004
• 期刊: The Journal of molecular diagnostics : JMD
• 作者: Taylor,MarciaL;Sehgal,Devinder;Raffeld,Mark;Obiakor,Harold;Akin,Cem;Mage,RoseG;Metcalfe,DeanD
• 通讯作者: Metcalfe,DeanD

Gene conversion and hypermutation during diversification of VH sequences in developing splenic germinal centers of immunized rabbits.

免疫兔脾生发中心发育过程中 VH 序列多样化过程中的基因转换和超突变。

• 发表时间: 1999
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Schiaffella,E;Sehgal,D;Anderson,AO;Mage,RG
• 通讯作者: Mage,RG

Developing neonatal rabbit appendix, a primary lymphoid organ, is seeded by immature blood-borne B cells: evidence for roles for CD62L/PNAd, CCR7/CCL21, alpha4beta1 and LFA-1.

发育中的新生兔阑尾是一种主要淋巴器官，由未成熟的血源性 B 细胞播种：CD62L/PNAd、CCR7/CCL21、α4β1 和 LFA-1 作用的证据。

• DOI: 10.1016/j.dci.2004.01.003
• 发表时间: 2004
• 期刊: Developmental and comparative immunology
• 影响因子: 2.9
• 作者: Sinha,RajeshK;Mage,RoseG
• 通讯作者: Mage,RoseG