Structural variation of the monoamine oxidase A gene promoter repeat polymorphism in nonhuman primates

By conferring allele‐specific transcriptional activity on the monoamine oxidase A (MAOA) gene in humans, length variation of a repetitive sequence [(variable number of tandem repeat (VNTR)] in the MAOA promoter influences a constellation of personality traits related to aggressive and antisocial behavior and increases the risk of neurodevelopmental and psychiatric disorders. Here, we have analyzed the presence and variability of this MAOA promoter repeat in several species of nonhuman primates. Sequence analysis of MAOA's transcriptional control region revealed the presence of the VNTR in chimpanzee (Pan troglodytes), bonobo (Pan paniscus), gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus), rhesus macaque (Macaca mulatta) and Gelada baboon (Theropithecus gelada). The majority of P. troglodytes and P. paniscus showed a single repeat with a sequence identical to the VNTR sequence in humans. In contrast, analyses of the remaining species revealed shorter sequences similar to the first 18 bp of human VNTR. Compared with other nonhuman primates, the VNTR sequence of M. mulatta showed the highest length variability with allele frequencies of 35, 25 and 40% for the five, six and seven repeat variants, respectively. The extent of variability of the MAOA promoter repeat in both rhesus monkeys and humans supports the notion that there may be a relationship between functional MAOA expression and aggression‐related traits in humans and rhesus macaque populations.

[1]  S. Pellis,et al.  The Influence of Phylogeny on the Social Behaviour of Macaques (Primates: Cercopithecidae, genus Macaca) , 2000 .

[2]  J. Kennedy,et al.  MAOA and persistent, pervasive childhood aggression , 2004, Molecular Psychiatry.

[3]  X. Breakefield,et al.  Localization of human monoamine oxidase-A gene to Xp11.23-11.4 by in situ hybridization: implications for Norrie disease. , 1989, Genomics.

[4]  L. Kochersperger,et al.  Immunocytochemical localization of monoamine oxidases A and B in human peripheral tissues and brain. , 1987, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[5]  P. Gaspar,et al.  Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. , 1995, Science.

[6]  K. Lesch,et al.  Serotonin transporter gene polymorphism, differential early rearing, and behavior in rhesus monkey neonates , 2002, Molecular Psychiatry.

[7]  P. Seeburg,et al.  cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[8]  R. Ebstein,et al.  Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA) , 2002, Molecular Psychiatry.

[9]  T. Mohandas,et al.  Human monoamine oxidase A and B genes map to Xp 11.23 and are deleted in a patient with Norrie disease. , 1989, Genomics.

[10]  K. Lesch,et al.  Association analysis of the functional monoamine oxidase A gene promoter polymorphism in psychiatric disorders. , 2001, American journal of medical genetics.

[11]  M. Youdim,et al.  EFFECTS OF MONOAMINE OXIDASE INHIBITION BY CLORGYLINE, DEPRENIL OR TRANYLCYPROMINE ON 5‐HYDROXYTRYPTAMINE CONCENTRATIONS IN RAT BRAIN AND HYPERACTIVITY FOLLOWING SUBSEQUENT TRYPTOPHAN ADMINISTRATION , 1975, British journal of pharmacology.

[12]  Svante Pääbo,et al.  The mosaic that is our genome , 2003, Nature.

[13]  Robert Plomin,et al.  Association analysis of MAOA and COMT with neuroticism assessed by peers , 2003, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[14]  K. Terao,et al.  Variation of variable number of tandem repeat sequences in the 3′-untranslated region of primate dopamine transporter genes that affects reporter gene expression , 2002, Neuroscience Letters.

[15]  M. Nelen,et al.  Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. , 1993, Science.

[16]  S. C. Stoner.  Approaches to the treatment of depression. , 2002, Journal of the American Pharmaceutical Association.

[17]  K. Lesch,et al.  Early experience and serotonin transporter gene variation interact to influence primate CNS function , 2002, Molecular Psychiatry.

[18]  A. Caspi,et al.  Role of Genotype in the Cycle of Violence in Maltreated Children , 2002, Science.

[19]  M. Owen,et al.  Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder , 2003, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[20]  E. Paykel,et al.  Genetic associations with clinical characteristics in bipolar affective disorder and recurrent unipolar depressive disorder. , 2000, American journal of medical genetics.

[21]  P. Tyrer,et al.  Monoamine oxidase inhibitors in anxiety disorders. , 1988, Journal of psychiatric research.

[22]  D. Hamer,et al.  A functional polymorphism in the monoamine oxidase A gene promoter , 1998, Human Genetics.

[23]  M. Owen,et al.  Examining for association between candidate gene polymorphisms in the dopamine pathway and attention-deficit hyperactivity disorder: a family-based study. , 2001, American journal of medical genetics.

[24]  T G Schulze,et al.  Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder. , 2000, American journal of medical genetics.

[25]  B. Thierry,et al.  Covariation of Conflict Management Patterns across Macaque Species , 2001 .

[26]  Klaus-Peter Lesch,et al.  Monoamine oxidase A gene promoter variation and rearing experience influences aggressive behavior in rhesus monkeys , 2005, Biological Psychiatry.

[27]  M. Nöthen,et al.  Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. , 1999, Human molecular genetics.