Mutational analysis of the human MAOA gene.
Level 4 - case-series / case-control
Cross-sectional genetic sequencing study in a sample of control individuals.
PubMed 8678123 · doi:10.1002/(SICI)1096-8628(19960216)67:1<92::AID-AJMG16>3.0.CO;2-K
What was done
Researchers evaluated the coding sequence of the human MAOA gene in 40 control males displaying a greater than 100-fold variation in MAO-A enzyme activity in cultured skin fibroblasts. Coding variations were screened and identified using reverse transcription-polymerase chain reaction (RT-PCR), single-strand conformation polymorphism (SSCP) analysis, and direct sequencing of mRNA or genomic DNA.
What was found
The MAOA coding region demonstrated high sequence conservation. Only 5 polymorphisms were detected across the 40 subjects. Four of these were in the third codon position and were synonymous (did not alter the amino acid sequence). The single non-synonymous variation resulted in a conservative lysine-to-arginine (Lys -> Arg) substitution that was predicted to be neutral and not affect protein structure.
Why it matters
These findings indicate that large variations in baseline MAO-A enzymatic activity are not caused by structural coding mutations in the MAOA gene, pointing instead toward regulatory or non-coding mechanisms. The study also validated genomic DNA primer sets to enable screening of MAOA mutations in clinical populations with neuropsychiatric conditions.
Limits
The study evaluated a small sample (40 males) and was restricted to control subjects. Analysis was focused on the coding sequence, leaving non-coding regulatory, promoter, and intronic regions unexamined.
Cited by
- context A subsequent study identified rare MAOA mutations in several other impulsively aggressive boys referred to a hospital.