Progress 09/11/03 to 07/31/09
Outputs
OUTPUTS: Genetic Resources for Non-Human Primates Our long-range goal was to provide and facilitate non-human primate genetic resources so that more controlled and direct comparisons can be made between human and non-human primates, thereby reducing the variables attributed to genetics in their study design and research. Our objective was to establish a "Primate Genetics Core", at the California National Primate Research Center (CNPRC), that would facilitate the use of correct genetic resources, develop new non-human primate genetic resources, and assist research activities that require, and can benefit from, a genetic component to their study design. Although a majority of faculty of the CNPRC were supportive of the concept of a "Genetics Core", the base-grant renewal did not support this effort, thus, this grant funding was independent from the CNPRC base-grant funding. The DNA bank developed under Specific Aim 1 focused on the primates at the CNPRC, this grant supplying the funds for the blood draws and all sample processing and personnel. As part of an initial start-up package for Dr. Lyons arrival at UC Davis in Fall, 1999, basic instrumentation and laboratory space was provided at the CNPRC. Once the new facility for Dr. Lyons laboratory open in 2004, the instrumentation and resources were combined at the new facility in the Center for Companion Animal Health and space was relinquished at the CNPRC. Dr. Lutz Foenicke provided the major oversight for the projects. Eleven (11) manuscripts are published to date, at least five (5) additional manuscripts submitted or in preparation by our research group or collaborators. The CNPRC genetics core accomplished resource development through three specific aims. Specific Aim 1: Create a warehouse for currently available genetic resources for non-human primates, specifically but not exclusively, for the rhesus macaque. Samples from over 4,500 individuals of the CNPRC are now banked and available to researchers. The half-sib families for linkage mapping have been expanded to 345 samples and are available for distribution. The sample collection also focused on "colony founders" and "progeny-rich individuals" to achieve sample collection representative of the genetic diversity in the colony. PARTICIPANTS: Genesio Karere, PhD - graduate student Lutz Freonicke, PhD - Post-doctoral fellow Lee Millon, BS - technician Jennifer A. Grahn - Technician Leslie Bach - graduate student The following list is of projects that we have provided assistance in their development and in attempts to obtain funding: i. D. Smith - (Department of Anthropology)- Subspecies characterizations of rhesus macaques ii. CNPRC - SPF Colony Development (funded) iii. C. VandeVoort - (CNPRC - DRG unit)- Alcoholism iv. C. VandeVoort - (CNPRC - DRG unit) - Stem cell research (Feb 01. submission) v. C. VandeVoort - (CNPRC - DRG unit) - Smoke effects on fertility vi. J. Capitanio - (CNPRC - BMB unit) - Alcoholism vii. J. Capitanio - (CNPRC - BMB Unit) - Genes influencing behavior viii. M. Golub - (CNPRC - BMB unit) - Benzene Susceptibility ix. C. Plopper - (CNPRC - Respiratory unit) - supplement to asthma PPG (March 01 submission) x. Fu-Tong Liu - (UCDSM, Department of Dermatology) - Galectin gene evolution xi. D. Orten - (Boys Town National Research Hospital) - Macular degeneration, deafness projects (both funded), DNA Request xii. Henrik Rasmussen, Sct. Hans Psychiatric Hospital, Denmark - DNA Request xiii. Vladimir Mayorov - (Mercer University) - DNA Request xiv. R. Laskey - (University of Texas) lead toxicity xv. J. Wine - (UCSF) - Cystic fibrosis model in rhesus macaques xvi. P. DeJong - (BACPAC Resources) - BAC Library characterization xvii. Ray Wack, - (Sacramento Zoo) - Chimpanzee parentage test xviii. Shoukhrat M. Mitalipov - (ONPRC) - Embryonic stem cell karyotyping TARGET AUDIENCES: Research scientists in non-human primates PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
Currently available genetic resources 1) Olive baboon and rhesus macaque BAC library filters, 2) DNA for a large half-sib set of rhesus macaque reference families, 3) DNA from the "Founder" animals of the current colony, 4) Genetic markers and microsatellites for the rhesus macaque, 5) Information on the gene pool and genetic diversity of the CNPRC colony, 6) DNA from other CNPRC primates (Titi Monkeys and Long-tailed macaques) 7) Assays for MAOA and Serotonin 5' HTTLR. 8) FISH probes to determine aenuploidy in rhesus macaques 9) A Radiation Hybrid 10,000 panel for the rhesus macaque.
Publications
- 6: Karere GM, Froenicke L, Millon L, Womack JE, Lyons LA. A high-resolution radiation hybrid map of rhesus macaque chromosome 5 identifies rearrangements in the genome assembly. Genomics. 2008 Oct;92(4):210-8. Epub 2008 Jul 31. PubMed PMID: 18601997; PubMed Central PMCID: PMC2605074.
- 7: Dupont C, Froenicke L, Lyons LA, Bavister BD, Brenner CA. Chromosomal instability in rhesus macaque preimplantation embryos. Fertil Steril. 2009 Apr;91(4):1230-7. Epub 2008 Apr 28. PubMed PMID: 18440514.
- 1: 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 Oct;38 Suppl 1:17-23. PubMed PMID: 19863674.
- 2: Kinnally EL, Tarara ER, Mason WA, Mendoza SP, Abel K, Lyons LA, Capitanio JP. Serotonin transporter expression is predicted by early life stress and is associated with disinhibited behavior in infant rhesus macaques. Genes Brain Behav. 2009 Aug 22. [Epub ahead of print] PubMed PMID: 19817873.
- 3: Hung PH, Froenicke L, Lin CY, Lyons LA, Miller MG, Pinkerton KE, VandeVoort CA. Effects of environmental tobacco smoke in vivo on rhesus monkey semen quality, sperm function, and sperm metabolism. Reprod Toxicol. 2009 Apr;27(2):140-8. Epub 2008 Dec 30. PubMed PMID: 19159676.
- 4: Karere GM, Kinnally EL, Sanchez JN, Famula TR, Lyons LA, Capitanio JP. What is an "adverse" environment Interactions of rearing experiences and MAOA genotype in rhesus monkeys. Biol Psychiatry. 2009 May 1;65(9):770-7. Epub 2008 Dec 21. PubMed PMID: 19103441; PubMed Central PMCID: PMC2688474.
- 5: Hung PH, Froenicke L, Lyons LA, VandeVoort CA. Nothing 'FISH'y about the rhesus macaque sex ratio. J Med Primatol. 2009 Feb;38(1):42-50. Epub 2008 Jul 30. PubMed PMID: 18671768.
- 8: Kinnally EL, Lyons LA, Abel K, Mendoza S, Capitanio JP. Effects of early experience and genotype on serotonin transporter regulation in infant rhesus macaques. Genes Brain Behav. 2008 Jun;7(4):481-6. Epub 2007 Dec 6. PubMed PMID: 18081711.
- 9: Froenicke L, Hung PH, VandeVoort CA, Lyons LA. Development of a non-human primate sperm aneuploidy assay tested in the rhesus macaque (Macaca mulatta). Mol Hum Reprod. 2007 Jul;13(7):455-60. Epub 2007 May 3. PubMed PMID: 17483087.
- 10: Froenicke L, Caldes MG, Graphodatsky A, Muller S, Lyons LA, Robinson TJ, Volleth M, Yang F, Wienberg J. Are molecular cytogenetics and bioinformatics suggesting diverging models of ancestral mammalian genomes Genome Res. 2006 Mar;16(3):306-10. PubMed PMID: 16510895; PubMed Central PMCID: PMC1415215.
- 11: Ferguson B, Capitanio J, Folks T, Hotchkiss C, Johnson Z, Kean L, Kubisch HM, Lank S, Lyons L, Miller GM, Nylander J, O'Connor D, Vallender EJ, Wiseman R. Resource brief: the National Non-Human Primate DNA Bank. Methods. 2009 Sep;49(1):3-4. PubMed PMID: 19706346.
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Progress 01/01/08 to 12/31/08
Outputs
OUTPUTS: Rhesus Macaque Reference Families The Lyons Laboratory has collected DNA for twelve half-sib families. These families will provide a resource for genetic linkage mapping of the rhesus macaque. Samples are collected as the colony is routinely screened for pathogens. The identification of these families was a result of the complete parentage testing of the colony by the VGL. Founder Animals for "Gene Mining" The second priority has been the collection of DNA from the animals that constitute the current genetic "founders" of the colony. These samples assist with monitoring the genetic diversity of the colony and provide a resource for researchers interested in screening the colony for specific genetic polymorphisms, "Gene Mining". The software package, "PEDSYS", developed by Dr. Bennett Dyke (SWNPRC), was used to identify the founders. Combined with the genetic data, this software package will allow the maintenance of genetic diversity in the colony and establish specific breeding lines. Approximately 302 animals have been identified as "Founders" for the colony. Information on the gene pool and genetic diversity of the CNPRC colony As a service to the CNPRC, the VGL has DNA fingerprinted approximately 95% of the rhesus macaque colony. These efforts continue as new macaques are born at the facility. Thus, researchers can now identify the kinship of primates used on their study projects and/or request primates of particular kinships. Researchers may choose to acquire primates that are closely related or unrelated, of the same populations or from different populations. This information would now also allow the exchange of genetically diverse primates across facilities. Studies involving two assays that characterize the rhesus macaque genes that regulate serotonin continue in association with Brain, Mind and Behavior Unit of the CNPRC (Dr. J. Capitanio). The first study focuses on serotonin transporter gene expression modulation by gene-environment interaction. The second behavioral study was an association study between variation in the upstream regulating region of the MAOA and behavior. PCR-based RH Mapping We have used PCR-based RH mapping to build a high-resolution map of rhesus macaque chromosome 5 (Mmul 5), the homolog of human chromosome 4. Genetic markers were developed based on 3'-UTR sequences available through the rhesus gene chip project (http://rhesusgenechip.unomaha.edu/ ) and MMUL_1 sequence data. In addition, 24 microsatellite markers ordered on the rhesus macaque meiotic linkage map have been typed. The Mmul 5 map (Figure 1) contains 372 markers spanning 4664.1 cR10,000 rad. The map provides a resolution of up to 30kb and indicates several amendments to the macaque genome sequence assembly. The RH data specify several smaller rearrangements not present in the genome assembly and show that two chromosomal translocations present in the genome sequence are likely generated by assembly artifacts PARTICIPANTS: Lutz Froenick, PhD - Post-doctoral Fellow Jennifer Grahn - DRA-V Supervisor Leslie Bach - PhD student in genetics Genesio Karere - PhD student in genetics Collaborations: i. D. Smith - (Department of Anthropology)- Subspecies characterizations of rhesus macaques ii. CNPRC - SPF Colony Development (funded) iii. C. VandeVoort - (CNPRC - DRG unit)- Alcoholism iv. C. VandeVoort - (CNPRC - DRG unit) - Stem cell research (Feb 01. submission) v. C. VandeVoort - (CNPRC - DRG unit) - Smoke effects on fertility vi. J. Capitanio - (CNPRC - BMB unit) - Alcoholism vii. J. Capitanio - (CNPRC - BMB Unit) - Genes influencing behavior xi. D. Orten - (Boys Town National Research Hospital) - Macular degeneration, deafness projects (both funded), DNA Request xii. Henrik Rasmussen, Sct. Hans Psychiatric Hospital, Denmark - DNA Request xiii. Vladimir Mayorov, Ph.D, - (Mercer University) - DNA Request xvi. P. DeJong, PhD - (BACPAC Resources) - BAC Library characterization xviii. Shoukhrat M. Mitalipov, Ph.D.: - (Oregon National Primate Research Center) - Embryonic stem cell karyotyping TARGET AUDIENCES: The main target audience in the scientific research community PROJECT MODIFICATIONS: No changes to the objectives and goals.
Impacts
The impact has mainly been to the scientific community. New reagents and assays have been developed for the rhesus macaque, including mapping tools and gene mutation tests. Currently available genetic resources include; 1) Olive baboon and rhesus macaque BAC library filters, 2) DNA for a large half-sib set of rhesus macaque reference families, 3) DNA from the "Founder" animals of the current colony, 4) Genetic markers and microsatellites for the rhesus macaque, 5) Information on the gene pool and genetic diversity of the CNPRC colony, 6) DNA from other CNPRC primates (Titi Monkeys and Long-tailed macaques)
Publications
- No publications reported this period
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Progress 01/01/07 to 12/31/07
Outputs
OUTPUTS: Rhesus Macaque Reference Families The Lyons Laboratory has collected DNA for twelve half-sib families, approximately 345 individuals. These families will provide a resource for genetic linkage mapping of the rhesus macaque. Samples are collected as the colony is routinely screened for pathogens. The identification of these families was a result of the complete parentage testing of the colony by the VGL. Founder Animals for "Gene Mining" The second priority has been the collection of DNA from the animals that constitute the current genetic "founders" of the colony. These samples assist with monitoring the genetic diversity of the colony and provide a resource for researchers interested in screening the colony for specific genetic polymorphisms, "Gene Mining". The software package, "PEDSYS", developed by Dr. Bennett Dyke (SWNPRC), was used to identify the founders. Combined with the genetic data, this software package will allow the maintenance of genetic diversity in the
colony and establish specific breeding lines. Approximately 302 animals have been identified as "Founders" for the colony. Information on the gene pool and genetic diversity of the CNPRC colony As a service to the CNPRC, the VGL has DNA fingerprinted approximately 95% of the rhesus macaque colony. These efforts continue as new macaques are born at the facility. Thus, researchers can now identify the kinship of primates used on their study projects and/or request primates of particular kinships. Researchers may choose to acquire primates that are closely related or unrelated, of the same populations or from different populations. This information would now also allow the exchange of genetically diverse primates across facilities. Studies involving two assays that characterize the rhesus macaque genes that regulate serotonin continue in association with Brain, Mind and Behavior Unit of the CNPRC (Dr. J. Capitanio). The first study focuses on serotonin transporter gene expression
modulation by gene-environment interaction. The second behavioral study was an association study between variation in the upstream regulating region of the MAOA and behavior. PCR-based RH Mapping We have used PCR-based RH mapping to build a high-resolution map of rhesus macaque chromosome 5 (Mmul 5), the homolog of human chromosome 4. Genetic markers were developed based on 3'-UTR sequences available through the rhesus gene chip project (http://rhesusgenechip.unomaha.edu/ ) and MMUL_1 sequence data. In addition, 24 microsatellite markers ordered on the rhesus macaque meiotic linkage map have been typed (Rogers et al. 2000; Rogers et al. 2006). The Mmul 5 map (Figure 1) contains 372 markers spanning 4664.1 cR10,000 rad. The map provides a resolution of up to 30kb and indicates several amendments to the macaque genome sequence assembly. The RH data specify several smaller rearrangements not present in the genome assembly and show that two chromosomal translocations present in the genome
sequence are likely generated by assembly artifacts
PARTICIPANTS: Lutz Froenick, PhD - Post-doctoral Fellow Jennifer Grahn - DRA-V Supervisor Leslie Bach - PhD student in genetics Genesio Karere - PhD student in genetics Collaborations: i. D. Smith - (Department of Anthropology)- Subspecies characterizations of rhesus macaques ii. CNPRC - SPF Colony Development (funded) iii. C. VandeVoort - (CNPRC - DRG unit)- Alcoholism iv. C. VandeVoort - (CNPRC - DRG unit) - Stem cell research (Feb 01. submission) v. C. VandeVoort - (CNPRC - DRG unit) - Smoke effects on fertility vi. J. Capitanio - (CNPRC - BMB unit) - Alcoholism vii. J. Capitanio - (CNPRC - BMB Unit) - Genes influencing behavior xi. D. Orten - (Boys Town National Research Hospital) - Macular degeneration, deafness projects (both funded), DNA Request xii. Henrik Rasmussen, Sct. Hans Psychiatric Hospital, Denmark - DNA Request xiii. Vladimir Mayorov, Ph.D, - (Mercer University) - DNA Request xvi. P. DeJong, PhD - (BACPAC Resources) - BAC Library characterization xviii. Shoukhrat M.
Mitalipov, Ph.D.: - (Oregon National Primate Research Center) - Embryonic stem cell karyotyping
TARGET AUDIENCES: The main target audience in the scientific research community.
PROJECT MODIFICATIONS: No changes to the objectives and goals.
Impacts
The impact has mainly been to the scientific community. New reagents and assays have been developed for the rhesus macaque, including mapping tools and gene mutation tests. Currently available genetic resources include; 1) Olive baboon and rhesus macaque BAC library filters, 2) DNA for a large half-sib set of rhesus macaque reference families, 3) DNA from the "Founder" animals of the current colony, 4) Genetic markers and microsatellites for the rhesus macaque, 5) Information on the gene pool and genetic diversity of the CNPRC colony, 6) DNA from other CNPRC primates (Titi Monkeys and Long-tailed macaques)
Publications
- Froenicke L, Hung P, VandeVoort CA, Lyons LA. Development of a non-human primate sperm aneuploidy assay tested in the rhesus macaque (Macaca mulatta). Molecular Human Reproduction, 13(7): 455-460, 2007.
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