Human monoamine oxidase A and B genes map to xp11.23 and are deleted in a patient with norrie disease

doi:10.1016/0888-7543(89)90279-6

Genomics

Volume 4, Issue 4, May 1989, Pages 552-559

https://doi.org/10.1016/0888-7543(89)90279-6 Get rights and content

Abstract

Monoamine oxidase A and B (MAO A and B) are the central enzymes that catalyze oxidative deamination of biogenic amines throughout the body. The regional locations of genes encoding MAO A and B on the X chromosome were determined by using full-length cDNA clones for human MAO A and B, respectively. Using somatic cell hybrids, in situ hybridization, and field-inversion gel electrophoresis as well as deletion mapping in a patient with Norrie disease, we concluded that these two genes are close to each other and to the DXS7 locus (Xp11.3).

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Cited by (187)

Hypomethylation of monoamine oxidase A promoter/exon 1 region is associated with temper outbursts in Prader-Willi syndrome
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Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder caused by the absence of paternally expressed and maternally imprinted genes on chromosome 15q 11.2–13. It is associated with a certain behavioural phenotype, especially temper outbursts with verbal and physical aggression towards others. Recent studies show a promising therapeutic effect of serotonin reuptake inhibitors like sertraline on frequency and intensity of outbursts. Monoamine oxidase A (MAOA) (X p11.23) plays a crucial role in the metabolism of monoamines. Dysregulation in methylation of the CpG island spanning the promoter region and exon 1 of MAOA is implicated in impulsive and aggressive behaviour.
In the present study, methylation rates of CpG dinucleotides in the MAOA promoter and exon 1 region were determined from DNA derived from whole blood samples of PWS patients (n = 32) and controls (n = 14) matched for age, sex and BMI via bisulfite sequencing. PWS patients were grouped into those showing temper outbursts, and those who do not.
Overall, PWS patients show a significant lower methylation rate at the promoter/exon 1 region than healthy controls in both sexes. Furthermore, PWS patients, male as well female with temper outbursts show a significant lower methylation rate than those without temper outbursts (p < 0.001 and p = 0.006).
The MAOA promoter/exon 1 region methylation seems to be dysregulated in PWS patients in sense of a hypomethylation, especially in those suffering from temper outbursts. This dysregulation probably plays a crucial role in the pathophysiology of temper outbursts in PWS.
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Citation Excerpt :
Both genes are highly conserved, as humans, rats, and bovine share ∼87 % MAOA sequence identity and ∼88 % MAOB sequence identity (Grimsby et al., 1991). In humans, MAOA and MAOB genes are located near the Xp11.3 region of the X-chromosome, separated by about 50 kilobases and oriented in a tail-to-tail (3′-3′) manner (Lan et al., 1989) (Fig. 2). The two genes share ∼70 % sequence identity and possess identical exon-intron organization, each with 15 exons and 14 introns (Chen et al., 1992).
Monoamine oxidase enzymes are responsible for the degredation of serotonin, dopamine, and norepinephrine in the central neurvous system. Although it has been nearly 100 years since they were first described, we are still learning about their role in the healthy brain and how they are altered in various disease states. The present review provides a survey of our current understanding of monoamine oxidases, with a focus on their contributions to neuropsychiatric, neurodevelopmental, and neurodegenerative disease. Important species differences in monoamine oxidase function and development in the brain are highlighted. Sex-specific monoamine oxidase regulatory mechanisms and their implications for various neurological disorders are also discussed. While our understanding of these critical enzymes has expanded over the last century, gaps exist in our understanding of sex and species differences and the roles monoamine oxidases may play in conditions often comorbid with neurological disorders.
The neurobiology of human aggressive behavior: Neuroimaging, genetic, and neurochemical aspects
2021, Progress in Neuro-Psychopharmacology and Biological Psychiatry
In modern societies, there is a strive to improve the quality of life related to risk of crimes which inevitably requires a better understanding of brain determinants and mediators of aggression. Neurobiology provides powerful tools to achieve this end. Pre-clinical and clinical studies show that changes in regional volumes, metabolism-function and connectivity within specific neural networks are related to aggression. Subregions of prefrontal cortex, insula, amygdala, basal ganglia and hippocampus play a major role within these circuits and have been consistently implicated in biology of aggression. Genetic variations in proteins regulating the synthesis, degradation, and transport of serotonin and dopamine as well as their signal transduction have been found to mediate behavioral variability observed in aggression. Gene-gene and gene-environment interactions represent additional important risk factors for aggressiveness. Considering the social burden of pathological forms of aggression, more basic and translational studies should be conducted to accelerate applications to clinical practice, justice courts, and policy making.
The role of monoamine oxidase A in the neurobiology of aggressive, antisocial, and violent behavior: A tale of mice and men
2020, Progress in Neurobiology
Citation Excerpt :
Plasma levels of DOPEG are particularly regarded as sensitive indices of MAOA activity (Sunderland et al., 1985). In humans, the MAOA gene is located on the X chromosome (Xp11.23) in a position adjacent to MAOB (Ozelius et al., 1988; Lan et al., 1989). The two genes share similar exon-intron organization, with 15 exons and ∼70 % sequence identity (Grimsby et al., 1991); furthermore, in both genes, the FAD-binding site is located on exon 12, which is highly conserved, with 93.9 % identity (Grimsby et al., 1991).
Over the past two decades, research has revealed that genetic factors shape the propensity for aggressive, antisocial, and violent behavior. The best-documented gene implicated in aggression is MAOA (Monoamine oxidase A), which encodes the key enzyme for the degradation of serotonin and catecholamines. Congenital MAOA deficiency, as well as low-activity MAOA variants, has been associated with a higher risk for antisocial behavior (ASB) and violence, particularly in males with a history of child maltreatment. Indeed, the interplay between low MAOA genetic variants and early-life adversity is the best-documented gene × environment (G × E) interaction in the pathophysiology of aggression and ASB. Additional evidence indicates that low MAOA activity in the brain is strongly associated with a higher propensity for aggression; furthermore, MAOA inhibition may be one of the primary mechanisms whereby prenatal smoke exposure increases the risk of ASB. Complementary to these lines of evidence, mouse models of Maoa deficiency and G × E interactions exhibit striking similarities with clinical phenotypes, proving to be valuable tools to investigate the neurobiological mechanisms underlying antisocial and aggressive behavior. Here, we provide a comprehensive overview of the current state of the knowledge on the involvement of MAOA in aggression, as defined by preclinical and clinical evidence. In particular, we show how the convergence of human and animal research is proving helpful to our understanding of how MAOA influences antisocial and violent behavior and how it may assist in the development of preventative and therapeutic strategies for aggressive manifestations.
A triarylboron based two-photon fluorescent probe for the detection of intracellular Monoamine oxidase by a reaction-induced aggregation
2020, Dyes and Pigments
Monoamine oxidases (MAOs) play vital roles in maintaining the homeostasis of biogenic amines by catalyzing their oxidation to the corresponding aldehydes. Recent studies have suggested that MAOs can be effective biomarkers for certain neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. To elucidate their distinct roles in different diseases, their selective detection is essential. In this study, we functionalized triarylboron compounds with the hydrophilic cyclen group, to develop novel fluorescent probe for detecting MAOs. TAB-1, TAB-2 and TAB-Br were synthesized, the hydrophilicity of the molecule was tuned by varying the number of diphenylamine and cyclen groups introduced into the structure. TAB-1 and TAB-2 exhibited significantly enhanced fluorescence in the presence of MAO A or MAO B. This is because their hydrophilic and flexible cyclen groups can be oxidized by MAOs to more hydrophobic and rigid molecular structure, which can reduce energy dissipation resulting from intramolecular motion. TAB-2 exhibit a more obvious aggregation phenomena than TAB-1 and a blueshift in the fluorescence spectra, thus allowing a ratiometric readout. Moreover, such a mechanism also provides a rapid response speed for MAOs. The introduction of TAB-2 into different live cells showed that it could differentiate the cells overexpressing MAO from other cells.
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Monoamine oxidase (MAOs) is involved in several psychiatric and neurological disorders. The specific detection of MAOs is of great significance to elucidate their functions in various biological processes. Currently, however, fast detection of MAOs remains a great challenge. It is, therefore, important to develop novel fluorescent probes for the monitoring of intracellular MAO activity. In this study, we synthesized OTPP-3-Piperazine and OTNP-3-Piperazine by functionalizing triarylphosphine with piperazine groups for MAO detection, using the rational design of molecular structures. OTNP-3-Piperazine demonstrated higher sensitivity to MAOs than OTPP-3-Piperazine because MAOs induced an AIE process via oxidation to produce water-insoluble oxidation products in OTNP-3-Piperazine. Such a recognition mechanism instantly responded to MAOs. OTNP-3-Piperazine was also introduced into different cells to explore its application as a biological probe. These results showed that it differentiated MAO-overexpressing cells from other cells, which demonstrated its promise as a biological fluorescent probe.

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Human monoamine oxidase A and B genes map to xp11.23 and are deleted in a patient with norrie disease

Abstract

Biochem. Pharmacol

Biochem. Pharmacol

Anal. Biochem

Biochem. Biophys. Res. Commun

Biochem. Pharmacol

Genomics

Cell

J. Mol. Biol

cDNA cloning of human monoamine oxidase A and B: Molecular differences between two forms of the enzyme

Recombinant DNA techniques for mapping the human X chromosome (abstract)

Clin. Genet

Genetic linkage between X-chromosome markers and bipolar affective illness

Nature (London)

On the Causes of Blindness in the Mentally Retarded

Tritiated pargyline binding to rat liver mitochondrial MAO

An improved method for G-banding chromosomes after in situ hybridization

Cytogenet. Cell Genet

Electrophoretic separation of large DNA molecules by periodic inversion of the electric field

Science

Differences in A and B forms of monoamine oxidase revealed by limited proteolysis and peptide mapping

Nature (London)