title: Molecular analysis, mutation screening, and association study of adenylate cyclase type 9 gene (ADCY9) in mood disorders.
abstract: Chromosome 16p13 has been shown to display modest linkage signals for mood disorders in a number of studies. An interesting candidate gene in this region is the adenylate cyclase (AC) type 9 gene (ADCY9). ACs are critical in neuronal signaling, and perturbation of brain AC activity has been reported in mood disorder postmortem brains. ACs may also act as targets of antidepressants. Two distinct length transcripts for the ADCY9 gene have been reported, but molecular mechanisms are unknown. To investigate the potential role of ADCY9 in mood disorders, we clarified alternative poly(A) sites for the two mRNA species, delineated the exon-intron structure, and screened the gene for genetic variants. The two transcripts encoded by ADCY9 shared the first 10 exons, but exon 11 was shorter in one of the mRNA species. Seven single nucleotide polymorphisms, including a missense mutation and one polymorphic microsatellite repeat in the 3'-UTR, were identified. However, a case-control study using the missense polymorphism, 2316A>G (Ile772Met), and the tetranucleotide repeat (TTTA)n showed no significant association with mood disorders in Japanese samples. The DNA polymorphisms detected in this study can be tested in other ethnic samples and/or other psychiatric diseases.
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Eiji
authors.initials: E
authors.lastname: Hattori
authors.forename: Joanne
authors.initials: J
authors.lastname: Meerabux
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Koji
authors.initials: K
authors.lastname: Saito
authors.forename: Haruo
authors.initials: H
authors.lastname: Shibuya
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nankai
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000262:Adenylyl Cyclases / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D001714:Bipolar Disorder / Q000201:enzymology / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D003866:Depressive Disorder / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA
chemical_list: D018076:DNA, Complementary; D000262:Adenylyl Cyclases; C413923:adenylate cyclase 9