This web page was produced as an assignment for Genetics 564, an undergraduate course at UW‐Madison.
The MAOA gene
The MAOA gene is located on the short arm (p) of the X chromosome at position 11.3. [1] The MAOA gene regulates the expression of monoamine oxidase A, an enzymatic protein that breaks down important neurotransmitters in the brain, including dopamine, norepinephrine, and serotonin. [2]
Symbol
Full name Locus tag Location Organism Gene type Gene length Accession GI number DNA sequence |
: MAOA
: monoamine oxidase A : RP1-201D17__B.2 : Xp11.3 : Homo sapiens : protein coding : 156040895 bp : NC_000023.11 : 568815575 : FASTA |
Polymorphism
Humans have various forms of the MAOA gene. At around 1.2kb upstream of the MAOA coding sequences, there is
a 30-base sequence that exists in 2, 3, 3.5, 4, or 5 repeats. This affects transcriptional activity of the MAOA gene promoter. In a study that did not include the 2 repeats variant, it was found that alleles with 3.5 or 4 repeats (high-activity form; H-MAOA) are transcribed 2 to 10 times more efficiently compared to alleles with 3 or 5 repeats (low-activity form; L-MAOA). [5]
This polymorphism results in two cDNA variants— Transcript Variant 1 and Transcript Variant 2, encoding proteins Isoform 1 and Isoform 2 respectively. Transcript Variant 2 contains an alternate exon in the 5' UTR and uses a downstream in-frame start codon, giving rise to Isoform 2 which has a shorter N-terminus compared to Isoform 1. [6]
H-MAOA is linked to depression while L-MAOA is known to be associated with aggression. Studies also discovered that the 2 repeats allele is associated with an increase in the likelihood of committing serious crime or violence. [7,8]
a 30-base sequence that exists in 2, 3, 3.5, 4, or 5 repeats. This affects transcriptional activity of the MAOA gene promoter. In a study that did not include the 2 repeats variant, it was found that alleles with 3.5 or 4 repeats (high-activity form; H-MAOA) are transcribed 2 to 10 times more efficiently compared to alleles with 3 or 5 repeats (low-activity form; L-MAOA). [5]
This polymorphism results in two cDNA variants— Transcript Variant 1 and Transcript Variant 2, encoding proteins Isoform 1 and Isoform 2 respectively. Transcript Variant 2 contains an alternate exon in the 5' UTR and uses a downstream in-frame start codon, giving rise to Isoform 2 which has a shorter N-terminus compared to Isoform 1. [6]
H-MAOA is linked to depression while L-MAOA is known to be associated with aggression. Studies also discovered that the 2 repeats allele is associated with an increase in the likelihood of committing serious crime or violence. [7,8]
mRNA Variant 1
Gene length Accession GI number mRNA sequence |
mRNA Variant 2
Gene length Accession GI number mRNA sequence |
Pathological mutation
A missense mutation that yields a premature stop codon in the eighth exon of the MAOA gene is known to result in complete MAOA deficiency. This mutation was detected in Brunner Syndrome patients with phenotypes like mild mental retardation, tendency to aggressive outbursts and violent impulsive behaviors. [2]
References:
- MAOA monoamine oxidase A. National Center for Biotechnology Information. Retrieved Feb 20, 2014.
- Brunner, H.G., et al. (1993). Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A.
Science, 262(5133), 578-580. - Karyotype image: http://www.pathology.washington.edu/galleries/cytogallery/images/mgk.jpg
- MAOA gene location image: http://www.genecards.org/pics/loc/MAOA-gene.png
- Sabol, S.Z., Hu, S., & Hamer, D. (1998). A functional polymorphism in the monoamine oxidase A gene promoter. Human Genetics,
103 (3), 273–9. - MAOA monoamine oxidase A [Homo sapiens (human)]. Genetics Home Reference. Retrieved Feb 20, 2014.
- Guo, G., Ou, X.M., Roettger, M., & Shih, J.C. (2008). The VNTR 2 repeat in MAOA and delinquent behavior in adolescence and young adulthood: associations and MAOA promoter activity. European Journal of Human Genetetics, 16(5): 626–34.
- Beaver K.M., Wrightb, J.P., Boutwelic, B.B., Bamesd, J.C., DeLisie, M., & Vaughnf, M.G. (2012). Exploring the association between the 2-repeat allele of the MAOA gene promoter polymorphism and psychopathic personality traits, arrests, incarceration, and lifetime antisocial behavior. Personality and Individual Differences, 54( 2), 164–168.