RESUMO
We have recently described a family in which there is cosegregation of major affective disorder with Darier's disease and have mapped this autosomal dominant skin disorder to 12q23-q24.1. This has provided an interesting candidate region for genetic studies of bipolar disorder. We have studied the segregation of seven markers spanning the Darier's disease locus in 45 bipolar disorder pedigrees and found modest evidence in support of linkage under heterogeneity for 5 of these markers. Nonparametric analyses were suggestive of linkage with a marker at the gene encoding a secretory form of phospholipase A2. Our sample has relatively low power to detect linkage under heterogeneity and independent researchers should examine markers from this region in further samples of bipolar pedigrees.
Assuntos
Transtorno Bipolar/genética , Cromossomos Humanos Par 12/genética , Doença de Darier/genética , Ligação Genética , Alelos , Transtorno Bipolar/enzimologia , Mapeamento Cromossômico , Feminino , Genes Dominantes , Marcadores Genéticos , Genótipo , Humanos , Escore Lod , Masculino , Linhagem , Fosfolipases A/genética , Fosfolipases A2RESUMO
Several pieces of evidence are consistent with the involvement of dopamine neurotransmission in the aetiology of bipolar disorder. We have tested the hypothesis that the functional mutation Ser311-->Cys of the dopamine D2 receptor gene confers susceptibility to bipolar disorder. There was no increased frequency of the mutation in 82 bipolar probands compared with 72 controls, showing that this mutation is not involved in the pathogenesis of (at least) the vast majority of cases of bipolar disorder. Our findings are consistent with other evidence from linkage and association studies against the involvement of the dopamine D2 receptor in bipolar disorder.
Assuntos
Transtorno Bipolar/genética , Polimorfismo Genético , Receptores de Dopamina D2/genética , Alelos , Transtorno Bipolar/etnologia , Transtorno Bipolar/fisiopatologia , Códon/genética , Análise Mutacional de DNA , Genes , Predisposição Genética para Doença , Humanos , Mutação Puntual , Reação em Cadeia da Polimerase , Transtornos Psicóticos/genética , Esquizofrenia/genética , Reino Unido/epidemiologia , População Branca/genéticaRESUMO
Darier's disease is a rare autosomal dominant skin disorder in which there is abnormal adhesion between keratinocytes. It appears to be associated with an increased prevalence of neuropsychiatric disorders including mental retardation and epilepsy. In addition we have previously reported a family in which major affective disorder cosegregates with Darier's disease. In the present study we have localized the gene for Darier's disease to chromosome 12q23-q24.1 by linkage analysis in five British pedigrees. We obtained a maximum two point lod score of 4.29 with marker D12S84 at zero recombination fraction. All five families showed evidence of linkage between the disease gene and markers in this region. Subsequent identification of the Darier's disease gene will provide insights into normal mechanisms of cell adhesion and may be of importance in the genetic investigation of neuropsychiatric disorders as well as elucidating the pathogenesis of Darier's disease itself.
