Assuntos
Transtorno Bipolar/genética , Proteínas de Ciclo Celular/genética , Cromossomos Humanos Par 12 , Proteínas Serina-Treonina Quinases/genética , Mapeamento Cromossômico , Citoesqueleto/fisiologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único , Deleção de Sequência , Sinapses/fisiologiaRESUMO
We previously reported linkage between bipolar disorder and a region on human chromosome (HC) 18q21. To identify genes in this region, exon trapping was performed on cosmids isolated from an HC18-specific cosmid library (LL18NC02) using 47 sequence tagged site (STS) markers from 18q21 as hybridization probes. A total of 285 unique sequences (exons) were obtained from 850 sequenced clones. Homology searching of the databases using NCBI's BLAST algorithms revealed that 31 exons have identity to known genes and/or ESTs, seven are identical to regions of finished genomic sequences in the 18q21 region, 20 have significant similarity (>30% sequence identity) to genes from human and/or other species, 19 were repetitive sequences, and 208 sequences (72%) are novel. Seventy per cent of the trapped sequences were predicted to be derived from genes using library screening and RT-PCR analyses. This represents an initial stage in characterizing genes in a susceptibility region for further study in bipolar disorder or other diseases that map to this region.
Assuntos
Transtorno Bipolar/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 18 , Éxons/genética , Animais , Células COS , Cosmídeos , Expressão Gênica , Biblioteca Gênica , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
A radioreceptor assay for tricyclic antidepressants described here is based on the ability of these drugs to compete with [3H]-3-quinuclidinyl benzilate (3H-QNB) for binding to muscarinic cholinergic receptors in rat brain membranes. The assay is sensitive, in that in can detect, for example, 2 ng/ml nortriptyline in plasma. Seven plasma samples from depressed patients treated with nortriptyline were assayed with the radioreceptor and gas liquid chromatographic methods, and the results from these two methods were almost identical. This assay should be used cautiously, if at all, in patients treated with other drugs that have potent anticholinergic effects.
