WNPRC GENETICS SERVICES UNIT

WNPRC 遗传学服务单位

• 批准号: 8173098
• 负责人: David H. O'Connor
• 金额: $ 10.33万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173098
• 关键词: AIDS Vaccines; Acquired Immunodeficiency Syndrome; Acute; Alleles; Allogenic; Ascaridil; Autologous; Base Sequence; Biological Assay; Breeding; CD8B1 gene; Cercocebus atys; Cercopithecus pygerythrus; Chinese People; Chronic; Cloning; Communicable Diseases; Complementary DNA; Computer Retrieval of Information on Scientific Projects Database; DNA; Detection; Educational workshop; Family suidae; Fee-for-Service Plans; Filipino; Funding; Genetic; Genetic Services; Genome; Genomics; Genotype; Grant; Immune; Immunogenetics; Infection; Institutes; Institution; International AIDS; Japan; Japanese Population; Laboratories; Lead; Length; Lymphoid Tissue; MHC Class I Genes; Macaca; Macaca mulatta; Major Histocompatibility Complex; Manuscripts; Methods; Microsatellite Repeats; Modeling; National Center for Research Resources; National Institute of Allergy and Infectious Disease; Price; Primates; Printing; Publications; RNA; Research; Research Personnel; Resolution; Resource Allocation; Resources; SIV; Sampling; Services; Source; T-Lymphocyte; Tail; Technology; Training; United States National Institutes of Health; Vaccinated; Vaccine Research; Variant; Virus; animal resource; base; bean; cohort; cost effective; genetic pedigree; genetic resource; interest; lectures; meetings; member; next generation; nonhuman primate; novel; pathogen; programs; repository; symposium; trafficking; working group

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To provide core, campus and non-host investigators with sophisticated and specialized genetics resources and expertise. Progress and concerns: In 2009 Genetics Services continued to aggressively develop new high resolution MHC genotyping in rhesus, cynomolgus and pig-tailed macaques using next generation sequencing technology. In addition, we have begun to expand our efforts to other nonhuman primates of experimental interest such as sooty mangabeys, African green monkeys and Japanese macaques. Microsatellite-based haplotyping has been used extensively for genotyping of Mauritian-origin cynomolgus macaques as well as sample authentication and pedigree verification. Specialized MHC genotyping services are also available for Indian- and Chinese-origin rhesus macaques, pig-tailed macaques, and cynomolgus macaques from various geographic origins. Genetics Services is taking the lead in developing high-resolution, sensitive, and economical assays for comprehensive MHC genotyping in macaques. During 2009, this included a major expansion of our fee-for-service program for high throughput, sequence-based MHC class I genotyping using Roche/454 next-generation platforms for external investigators. We are currently genotyping NHP cohorts from simian immune deficiency virus studies as well as characterizing breeding colonies. Allocation of resource access: The Genetics Service provided MHC genotyping support to more than two dozen laboratories around the world in 2009. In addition, we participated in the NCRR Primate Centers Working Group on Genetics and Genomics, as well as the Genome Banking Working Group that has generated a large repository of genomic DNA samples from various nonhuman primates including WNPRC rhesus and cynomolgus macaques. We are also contributing our expertise as members of the Working Group for the Primate Portal. Dissemination: Dr. O'Connor, the PI for Genetics Services, and Dr. Wiseman presented multiple lectures and authored nine publications on NHP genetics (see below). We request that projects utilizing Genetics Service acknowledge the service in manuscripts and presentations. Training: Methods for MHC genotyping are regularly discussed during scientific conferences attended by Dr. O'Connor and his staff. In 2009, this included multiple presentations for the International AIDS Vaccine Initiative (IAVI) and at the NIH for NIAID, NCRR, DIADS & the Vaccine Research Program. In addition, lectures were given at the following scientific meetings: + Detection, Impact and Control of Specific Pathogens in Animal Resource Facilities Workshop sponsored by NCRR/NIA + Tsukuba Primate Research Center, National Institute of Infectious Diseases, Japan + 27th Annual Symposium for Nonhuman Primate Models for AIDS PUBLICATIONS: Campbell KJ, Detmer AM, Karl JA, Wiseman RW, Blasky AJ, Hughes AL, Bimber BN, O'Connor SL, O'Connor DH. Characterization of 47 MHC class I sequences in Filipino cynomolgus macaques. Immunogenetics. 2009 61(3): 177-87. Burwitz BJ, Pendley CJ, Greene JM, Detmer AM, Lhost JJ, Karl JA, Piaskowski SM, Rudersdorf RA, Wallace LT, Bimber BN, Loffredo JT, Cox DG, Bardet W, Hildebrand W, Wiseman RW, O'Connor SL, O'Connor DH. Mauritian cynomolgus macaques share two exceptionally common major histocompatibility complex class I alleles that restrict simian immunodeficiency virus-specific CD8+ T cells. J Virol. 2009 83(12): 6011-9. Karl JA, Wiseman RW, O'Connor DH. Cost-effective sequence-based nonhuman primate MHC class I genotyping from RNA. Methods. 2009 49(1): 11-7. Wiseman RW, Karl JA, Bimber BN, O'Leary CE, Lank SM, Tuscher JJ, Detmer AM, Bouffard P, Levenkova N, Turcotte CL, Szekeres E Jr, Wright C, Harkins T, O'Connor DH. Major histocompatibility complex genotyping with massively parallel pyrosequencing. Nat Med. 2009 15(11): 1322-6. O'Leary CE, Wiseman RW, Karl JA, Bimber BN, Lank SM, Tuscher JJ, O'Connor DH. Identification of novel MHC class I sequences in pig-tailed macaques by amplicon pyrosequencing and full-length cDNA cloning and sequencing. Immunogenetics. 2009 61(10): 689-701. Valentine LE, Loffredo JT, Bean AT, Le¿n EJ, MacNair CE, Beal DR, Piaskowski SM, Klimentidis YC, Lank SM, Wiseman RW, Weinfurter JT, May GE, Rakasz EG, Wilson NA, Friedrich TC, O'Connor DH, Allison DB, Watkins DI. Infection with "escaped" virus variants impairs control of simian immunodeficiency virus SIVmac239 replication in Mamu-B*08-positive macaques. J Virol. 2009 83(22): 11514-27. Kanthaswamy S, Capitanio JP, Dubay CJ, Ferguson B, Folks T, Ha JC, Hotchkiss CE, Johnson ZP, Katze MG, Kean LS, Kubisch HM, Lank S, Lyons LA, Miller GM, Nylander J, O'Connor DH, Palermo RE, Smith DG, Vallender EJ, Wiseman RW, Rogers J. Resources for genetic management and genomics research on non-human primates at the National Primate Research Centers (NPRCs). J Med Primatol. 2009 38 Suppl 1: 17-23. Bolton DL, Minang JT, Trivett MT, Song K, Tuscher JJ, Li Y, Piatak M Jr, O'Connor D, Lifson JD, Roederer M, Ohlen C. Trafficking, persistence, and activation state of adoptively transferred allogeneic and autologous Simian Immunodeficiency Virus-specific CD8(+) T cell clones during acute and chronic infection of rhesus macaques. J Immunol. 2010 184(1): 303-14. Greene JM, Lhost JJ, Burwitz BJ, Budde ML, Macnair CE, Weiker MK, Gostick E, Friedrich TC, Broman KW, Price DA, O'Connor S, O'Connor DH. Extra-lymphoid tissue-resident CD8+ T cells from SIVmac239Deltanef-vaccinated macaques suppress SIVmac239 replication ex vivo. J Virol. 2010 Jan 20.[Epub ahead of print].

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 目标：为核心、校园和非宿主研究人员提供先进和专业的遗传资源和专业知识。 进展和关注点： 2009 年，Genetics Services 继续利用新一代测序技术积极开发恒河猴、食蟹猴和猪尾猕猴的新型高分辨率 MHC 基因分型。此外，我们还开始将研究范围扩大到其他具有实验意义的非人类灵长类动物，例如乌白眉猴、非洲绿猴和日本猕猴。基于微卫星的单倍型分析已广泛用于毛里求斯猕猴的基因分型以及样本认证和谱系验证。我们还为来自不同地理来源的印度和中国恒河猴、猪尾猕猴和食蟹猴提供专门的 MHC 基因分型服务。 Genetics Services 正在率先开发用于猕猴综合 MHC 基因分型的高分辨率、灵敏且经济的检测方法。 2009 年期间，这包括对我们的按服务收费计划进行了重大扩展，以使用 Roche/454 下一代平台为外部研究人员提供高通量、基于序列的 MHC I 类基因分型。我们目前正在对来自猿猴免疫缺陷病毒研究的 NHP 群体进行基因分型，并对繁殖群体进行特征分析。 资源访问的分配： 2009 年，遗传学服务机构为全球超过 20 个实验室提供了 MHC 基因分型支持。此外，我们还参加了 NCRR 灵长类动物中心遗传学和基因组学工作组，以及基因组库工作组，该工作组已生成了来自各种非人类灵长类动物（包括 WNPRC 恒河猴和食蟹猴）的基因组 DNA 样本的大型存储库。 作为灵长类动物门户工作组的成员，我们还贡献了我们的专业知识。 传播： 遗传学服务 PI 奥康纳 (O'Connor) 博士和怀斯曼 (Wiseman) 博士发表了多次讲座，并撰写了 9 篇关于 NHP 遗传学的出版物（见下文）。我们要求利用遗传学服务的项目在手稿和演示文稿中承认该服务。 训练： O'Connor 博士及其工作人员参加的科学会议定期讨论 MHC 基因分型方法。 2009 年，这包括在国际艾滋病疫苗倡议 (IAVI) 以及在 NIH 上为 NIAID、NCRR、DIADS 和疫苗研究计划进行的多次演讲。 此外，还在以下科学会议上进行了讲座： + 动物资源设施中特定病原体的检测、影响和控制研讨会由 NCRR/NIA 赞助 + 日本国立传染病研究所筑波灵长类动物研究中心 + 第 27 届非人类灵长类艾滋病模型年度研讨会 出版物： 坎贝尔 KJ、德特默 AM、卡尔 JA、怀斯曼 RW、布拉斯基 AJ、休斯 AL、比伯 BN、奥康纳 SL、奥康纳 DH。菲律宾食蟹猴 47 个 MHC I 类序列的表征。免疫遗传学。 2009 61(3): 177-87。 Burwitz BJ、Pendley CJ、Greene JM、Detmer AM、Lhost JJ、Karl JA、Piaskowski SM、Rudersdorf RA、Wallace LT、Bimber BN、Loffredo JT、Cox DG、Bardet W、Hildebrand W、Wiseman RW、O'Connor SL、O'Connor DH。毛里求斯食蟹猴有两个极其常见的主要组织相容性复合体 I 类等位基因，它们限制了猿猴免疫缺陷病毒特异性 CD8+ T 细胞。 J·维罗尔. 2009 83(12): 6011-9。 卡尔·JA、怀斯曼 RW、奥康纳 DH。基于 RNA 的经济有效的基于序列的非人灵长类 MHC I 类基因分型。方法。 2009 49(1): 11-7。 Wiseman RW、Karl JA、Bimber BN、O'Leary CE、Lank SM、Tuscher JJ、Detmer AM、Bouffard P、Levenkova N、Turcotte CL、Szekeres E Jr、Wright C、Harkins T、O'Connor DH。主要组织相容性复杂基因分型与大规模并行焦磷酸测序。纳特医学。 2009 15(11): 1322-6。 O'Leary CE、Wiseman RW、Karl JA、Bimber BN、Lank SM、Tuscher JJ、O'Connor DH。通过扩增子焦磷酸测序和全长 cDNA 克隆和测序鉴定猪尾猕猴中新的 MHC I 类序列。免疫遗传学。 2009 61(10): 689-701。 Valentine LE、Loffredo JT、Bean AT、Le¿n EJ、MacNair CE、Beal DR、Piaskowski SM、Klimentidis YC、Lank SM、Wiseman RW、Weinfurter JT、May GE、Rakasz EG、Wilson NA、Friedrich TC、O'Connor DH、Allison DB、Watkins DI。 “逃逸”病毒变体的感染会损害 Mamu-B*08 阳性猕猴中对猿猴免疫缺陷病毒 SIVmac239 复制的控制。 J·维罗尔. 2009 83(22): 11514-27。 Kanthaswamy S、Capitanio JP、Dubay CJ、Ferguson B、Folks T、Ha JC、Hotchkiss CE、Johnson ZP、Katze MG、Kean LS、Kubisch HM、Lank S、Lyons LA、Miller GM、Nylander J、O'Connor DH、Palermo RE、Smith DG、Vallender EJ、Wiseman RW、Rogers J。 资源 国家灵长类研究中心 (NPRC) 对非人类灵长类动物进行遗传管理和基因组学研究。 J Med Primatol。 2009 年 38 增刊 1：17-23。 Bolton DL, Minang JT, Trivett MT, Song K, Tuscher JJ, Li Y, Piatak M Jr, O'Connor D, Lifson JD, Roederer M, Ohlen C. 恒河猴急性和慢性感染期间过继转移的同种异体和自体猿免疫缺陷病毒特异性 CD8(+) T 细胞克隆的贩运、持久性和激活状态 猕猴。 J免疫学杂志。 2010 184(1): 303-14。 Greene JM、Lhost JJ、Burwitz BJ、Budde ML、Macnair CE、Weiker MK、Gostick E、Friedrich TC、Broman KW、Price DA、O'Connor S、O'Connor DH。来自接种 SIVmac239Deltanef 的猕猴的淋巴组织外驻留 CD8+ T 细胞可抑制 SIVmac239 离体复制。 J·维罗尔. 2010 年 1 月 20 日。[印刷前的电子版]。