Abstract # 212:

Scheduled for Saturday, August 19, 2006 08:15 AM-08:30 AM: Session 20 (Regency East #3) Oral Presentation

Behavioral genetics of monoamine regulatory genes in the cynomolgus macaque

C. M. Miller-Butterworth1, J. R. Kaplan2, S. B. Manuck3 and R. E. Ferrell1
1University of Pittsburgh, Dept of Human Genetics, A300 Crabtree Hall, 130 DeSoto St, Pittsburgh, PA 15261, USA, 2Wake Forest University School of Medicine, 3Dept of Psychology, University of Pittsburgh
     Cerebrospinal fluid concentrations of monoamine metabolites and certain behavioral phenotypes are significantly heritable in monkeys. Specific genotypes of the human monoamine pathway genes have been linked to personality traits and CNS monoamine metabolite concentrations. The dopamine (DAT) and serotonin (SERT) transporters regulate monoaminergic tone, and we therefore investigated whether sequence variation in these genes is associated with behavioral and monoamine metabolite differences previously identified between dominant and subordinate cynomolgus macaques, Macaca fascicularis. DNA, social rank and detailed behavioral observations were obtained from 500 M. fascicularis. Monoamine metabolite levels were collected from 100 monkeys. Sequence variation in the entire DAT and SERT genes was initially characterized in approximately 100 macaques. 85 polymorphisms were identified in ~4 kb of DAT exonic sequence. In contrast, 39 validated exonic SNPs are reported for human DAT, and macaque SERT exons also display considerably less variation. Genotype and allele frequencies were determined for each DAT SNP but none correlated with social status. Two DAT SNPs were non-synonymous and may produce functional gene variants. They and 3 SNPs in the 3’ untranslated region (UTR) were genotyped in 500 macaques; however no significant association with behavior or monoamine metabolite levels was identified. In further contrast to humans, the macaque DAT gene does not show significant long range linkage disequilibrium and the tandem repeat in the 3’ UTR does not vary in repeat number.