MUTATIONAL ANALYSIS OF THE HUMAN MAOA GENE

The monoamine oxidases (MAO-A and MAO-B) are the enzymes primarily res ponsible for the degradation of amine neurotransmitters, such as dopam ine, norepinephrine, and serotonin. Wide variations in activity of the se isozymes have been reported in control humans. The MAOA and MAOB ge nes are located next to each other in the p11.3-11.4 region of the hum an X chromosome. Our recent documentation of an MAO-A-deficiency state , apparently associated with impulsive aggressive behavior in males, h as focused attention on genetic variations in the MAOA gene. In the pr esent study, variations in the coding sequence of the MAOA gene were e valuated by RT-PCR, SSCP, and sequencing of mRNA or genomic DNA in 40 control males with >100-fold variations in MAO-A activity, as measured in cultured skin fibroblasts. Remarkable conservation of the coding s equence was found, with only 5 polymorphisms observed. All but one of these were in the third codon position and thus did not alter the dedu ced amino acid sequence. The one amino acid alteration observed, lys-- >arg, was neutral and should not affect the structure of the protein. This study demonstrates high conservation of coding sequence in the hu man MAOA gene in control males, and provides primer sets which can be used to search genomic DNA for mutations in this gene in males with ne uropsychiatric conditions. (C) 1996 Wiley-Liss, Inc.