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].