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Monoamine oxidase A gene promoter variation and rearing experience influences aggressive behavior in rhesus monkeys

Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, USA.
Biological Psychiatry (Impact Factor: 10.25). 02/2005; 57(2):167-72. DOI: 10.1016/j.biopsych.2004.10.012
Source: PubMed

ABSTRACT Allelic variation of the monoamine oxidase A (MAOA) gene has been implicated in conduct disorder and antisocial, aggressive behavior in humans when associated with early adverse experiences. We tested the hypothesis that a repeat polymorphism in the rhesus macaque MAOA gene promoter region influences aggressive behavior in male subjects.
Forty-five unrelated male monkeys raised with or without their mothers were tested for competitive and social group aggression. Functional activity of the MAOA gene promoter polymorphism was determined and genotypes scored for assessing genetic and environmental influences on aggression.
Transcription of the MAOA gene in rhesus monkeys is modulated by an orthologous polymorphism (rhMAOA-LPR) in its upstream regulatory region. High- and low-activity alleles of the rhMAOA-LPR show a genotype x environment interaction effect on aggressive behavior, such that mother-reared male monkeys with the low-activity-associated allele had higher aggression scores.
These results suggest that the behavioral expression of allelic variation in MAOA activity is sensitive to social experiences early in development and that its functional outcome might depend on social context.

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Available from: Jens Robert Wendland, Dec 26, 2013
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    • "Human genomes contain VNTRs within the 5= untranslated region (UTR) of the monoamine oxidase A (MAOA) gene, which are 30 bp in length with tandem repeats of three, four, or five (Sabol et al. 1998). Expression of the MAOA gene is related to aggressive character and behavior (Lawson et al. 2003; Newman et al. 2005; Wendland et al. 2006b; Alia-Klein et al. 2008), and the MAOA VNTR polymorphism in the 5= UTR region affects its transcription (Deckert et al. 1999). Connection studies between MAOA VNTR polymorphisms and the transcriptional regulation of the MAOA gene have been reported in humans (Beach et al. 2010; Guo et al. 2008; Pai et al. 2007). "
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    ABSTRACT: Variable number of tandem repeats (VNTRs) are scattered throughout the primate genome, and genetic variation of these VNTRs have been accumulated during primate radiation. Here, we analyzed VNTRs upstream of the monoamine oxidase A (MAOA) gene in 11 different gibbon species. An abundance of truncated VNTR sequences and copy number differences were observed compared to those of human VNTR sequences. To better understand the biological role of these VNTRs, a luciferase activity assay was conducted and results indicated that selected VNTR sequences of the MAOA gene from human and three different gibbon species (Hylobates klossii, Hylobates lar, and Nomascus concolor) showed silencing ability. Together, these data could be useful for understanding the evolutionary history and functional significance of MAOA VNTR sequences in gibbon species.
    Genome 10/2014; 57(8):1-6. DOI:10.1139/gen-2014-0065
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    • "In these studies, candidate genes are selected based on what is known in humans so as to establish the rhesus monkey as a reliable model for the study of the trait or pathology of interest. The most commonly studied genes in monkeys are those which genetic studies have identified as functionally equivalent genetic single nucleotide polymorphisms (SNPs) in rhesus monkeys to those found in humans, including the serotonin-transporter-linked polymorphic region (5-HTTLPR; Lesch et al. 1997), the µ-opioid receptor (OPRM1; Miller et al. 2004), the monoamine oxidase A (MAOA) gene promoter (Newman et al. 2005), and the corticotropin releasing hormone (CRH) promoter (Barr et al. 2008) and the brain-derived neurotrophic factor (BDNF) gene (Cirulli et al. 2011). Further research has expanded on the identification of these SNPs by genotyping individual subjects using DNA isolated from blood samples and associating particular genotypes with behaviors of interest (see Part II, below). "
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    ABSTRACT: This report reviews the scientific literature from the past several decades that focuses on nonhuman primates (NHPs) as models of neuropsychiatric disorders, including anxiety, and alcoholism. In particular, we highlight the approaches, advantages, and disadvantages of the rearing, genetic, and epigenetic methodologies behind these studies as a means of evaluating the application of these methods in assessing disorders in NHPs as models of human disease. Finally, we describe the contributions the NHP studies have made to neuropsychiatric research and areas for future research.
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    • "Although independently evolved (Lesch et al., 1997), the macaque polymorphism appears to regulate serotonin functioning (Bennett et al., 2002) and behavior (e.g., Bennett et al., 1998; Trefilov et al., 2000; Champoux et al., 2002; Barr et al., 2003; Bethea et al., 2004; Brent et al., 2013) in a manner similar to humans. Furthermore , although the STin2 VNTR polymorphism has not been identified in macaques, additional polymorphisms in SLC6A4 and other serotonin related genes have been identified in rhesus macaques that are similar to those found in humans (e.g., Newman et al., 2005; Vallender et al., 2008; Lindell et al., 2012). This suggests that parallel evolution of the serotonin system is occurring between the two species (Vallender et al., 2008). "
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    ABSTRACT: Serotonin has been repeatedly indicated as a biological marker of behavior. In particular, the serotonin transporter gene, SLC6A4, has been the focus of a large body of research. Interestingly, both rhesus macaques (Macaca mulatta) and humans have independently evolved a number of shared polymorphisms for this gene, which is indicative of parallel evolution between the two species. However, little is known about the evolution of this gene, particularly within macaques. Although there are several hypotheses as to the adaptive values of various polymorphisms, few authors have gone beyond theoretical discussion. Here, we examined the genetic variation in SLC6A4 within and between several species of macaques and investigate whether selection has played a significant role in its evolutionary history. In addition, we assayed the promoter region polymorphism, 5-HTTLPR, which is known to play a significant role in regulating both serotonin turnover and behavior. In examining the distribution of the 5-HTTLPR polymorphism, we identified significant differences between Indian and Chinese populations of Macaca mulatta; furthermore, we discovered its presence in Macaca cyclopis, which has not been described before. In regard to the evolutionary history of SLC6A4, we found little evidence for selection and conclude that SLC6A4 largely evolved through neutral processes, possibly due to its potential role in regulating behavioral plasticity. However, we also found very low levels of linkage between the coding regions and 5-HTTLPR. Because we limited evolutionary analyses to the coding regions, it is possible that the promoter region shows a distinct evolutionary history from SLC6A4. Am J Phys Anthropol, 2013. © 2013 Wiley Periodicals, Inc.
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