title: Analysis of a cluster of polymorphisms in AKT1 gene in bipolar pedigrees: a family-based association study.
abstract: We have previously performed a genome scan in 22 multiplex pedigrees with bipolar disorder and detected a moderate linkage signal on distal portion of chromosome 14q22-32. One of the large pedigrees displayed a parametric lod score >3 at a marker on 14q23-32. Upon inspection of genes located in this region revealed AKT1, a kinase that activates a lithium-responsive cell-survival pathway. Because lithium is an effective mood stabilizer for bipolar disorder patients, AKT1 is an interesting candidate for further investigation. We screened the gene for possible mutations and detected 14 polymorphisms. Seven polymorphic sites were clustered in a small segment spanning exon 14 and downstream intron. Transmission of haplotypes constructed from this cluster showed a weak evidence of association between the AKT1 and bipolar disorder.
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, 351-0198, Saitama, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Sevilla D
authors.initials: SD
authors.lastname: Detera-Wadleigh
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14; D005091:Exons; D006239:Haplotypes; D006801:Humans; D007438:Introns; D010375:Pedigree; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt
chemical_list: D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt