RESUMO
The human genome has linkage disequilibrium (LD) blocks, within which single-nucleotide polymorphisms show strong association with each other. We examined data from the International HapMap Project to define LD blocks and to detect DNA sequence features inside of them. We used permutation tests to determine the empirical significance of the association of LD blocks with genes and Alu repeats. Very large LD blocks (>200 kb) have significantly higher gene coverage and Alu frequency than the outcome obtained from permutation-based simulation, whereas there was no significant positive correlation between gene density and block size. We also observed a reduced frequency of Alu repeats at the gaps between large LD blocks, indicating that their enrichment in large LD blocks does not introduce recombination hotspots that would cause these gaps.
Assuntos
Elementos Alu , Genoma Humano , Desequilíbrio de Ligação , Bases de Dados de Ácidos Nucleicos , Genética Populacional , Humanos , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Recombinação GenéticaRESUMO
The human genome has linkage disequilibrium (LD) blocks, within which single-nucleotide polymorphisms show strong association with each other. We examined data from the International HapMap Project to define LD blocks and to detect DNA sequence features inside of them. We used permutation tests to determine the empirical significance of the association of LD blocks with genes and Alu repeats. Very large LD blocks (>200 kb) have significantly higher gene coverage and Alu frequency than the outcome obtained from permutation-based simulation, whereas there was no significant positive correlation between gene density and block size. We also observed a reduced frequency of Alu repeats at the gaps between large LD blocks, indicating that their enrichment in large LD blocks does not introduce recombination hotspots that would cause these gaps.
Assuntos
Humanos , Elementos Alu , Genoma Humano , Desequilíbrio de Ligação , Bases de Dados de Ácidos Nucleicos , Genética Populacional , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Recombinação GenéticaRESUMO
Several reports have suggested the presence of anticipation in bipolar affective disorder (BPAD). In addition, independent studies using the RED (repeat expansion detection) have shown association between BPAD and longer CAG/CTG repeats. Therefore loci with large CAG/CTG repeats are plausible candidates in the inheritance of BPAD. The present study assesses the length of the repeats in four loci: the ERDA-1 locus which is known to account for most of the long CAG repeats detected by RED, the SEF2-1b locus which is placed in a region where positive linkage results have been reported and the loci MAB21L and KCNN3 as functional candidate genes. A Brazilian case-control sample with 115 unrelated BPAD patients and 196 healthy control subjects and 14 multiply affected bipolar families was investigated. With the case-control design the distribution of alleles between the two groups did not approach statistical significance. The extended transmission disequilibrium test (ETDT) performed in our families did not show evidence for linkage disequilibrium. Parametric and non-parametric linkage analysis also did not provide support for linkage between any of the four loci and BPAD. Our data do not support the hypothesis that variation at the polymorphic CAG/CTG repeat loci ERDA-1, SEF2-1b, MAB21L or KCNN3 influence susceptibility to BPAD in our sample.
Assuntos
Transtorno Bipolar/genética , Proteínas de Ligação a DNA , Proteínas de Homeodomínio/genética , Polimorfismo Genético , Canais de Potássio Cálcio-Ativados , Canais de Potássio/genética , Transativadores/genética , Fatores de Transcrição , Repetições de Trinucleotídeos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Ligação Genética , Marcadores Genéticos , Genótipo , Sequências Hélice-Alça-Hélice , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Canais de Potássio Ativados por Cálcio de Condutância Baixa , Estatística como Assunto , Estatísticas não Paramétricas , Fatores de Transcrição TCF , Fator de Transcrição 4 , Proteína 2 Semelhante ao Fator 7 de TranscriçãoRESUMO
BACKGROUND: The incidence of schizophrenia among African-Caribbeans living in Britain has been frequently reported to be increased. We sought to determine whether the symptom profile in schizophrenic patients from this group differed from that of their White counterparts. METHODS: Factor analysis was applied to symptom data obtained by the Present State Examination (PSE) from a group of White (N = 96) and Afro-Caribbean (N = 64) patients who satisfied Research Diagnostic Criteria criteria for broad schizophrenia. We identified six symptom dimensions: mania, depression, first-rank delusions, other delusions, hallucinations and one which comprised both manic and catatonic symptoms. RESULTS: The only difference between the two ethnic groups was seen on the mixed mania-catatonia dimension with the Afro-Caribbean group being over-represented. There were no other significant differences between the groups. Discriminant analysis, however, revealed no significant differences between the groups in any dimension. CONCLUSIONS: These results indicate that there are no differences between White and African-Caribbean patients with schizophrenia in terms of the core symptoms of the disorder, however, the African-Caribbean patients may present with more symptoms of a mixed affective nature.
Assuntos
Esquizofrenia/diagnóstico , Esquizofrenia/etnologia , População Branca/psicologia , Adolescente , Adulto , Análise Discriminante , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Psicologia do Esquizofrênico , Reino Unido , Índias Ocidentais/etnologiaRESUMO
BACKGROUND: The high rate of schizophrenia among the second-generation African-Caribbean population in Britain has prompted much concern and speculation. Sugarman and Craufurd have reported that the morbid risk in the siblings of second-generation African-Caribbean schizophrenic patients was unusually high compared with that of the siblings of White patients. METHOD: We sought to replicate these findings by comparing the morbid risk for schizophrenia in the first-degree relatives of 111 White and 73 African-Caribbean psychotic probands. The latter comprised 35 first-generation (born in the Caribbean) and 38 second-generation (born in Britain) probands. RESULTS: The morbid risk for schizophrenia was similar for the parents and siblings of White and first-generation African-Caribbean patients, and for the parents of the second-generation African-Caribbean probands. However, the siblings of second-generation African-Caribbean psychotic probands had a morbid risk for schizophrenia that was seven times that of their White counterparts (P = 0.007); similarly, the siblings of second-generation African-Caribbean schizophrenic probands had a morbid risk for schizophrenia that was four times that of their White counterparts (P = 0.05). CONCLUSIONS: These findings replicate those of the earlier report of Sugarman and Craufurd, and suggest either that the second-generation African-Caribbean population in Britain is particularly vulnerable to some environmental risk factors for schizophrenia, or that some environmental factors act selectively on this population in Britain.
Assuntos
População Negra/genética , Negro ou Afro-Americano/psicologia , Transtornos Psicóticos/genética , Esquizofrenia/genética , População Branca/genética , População Branca/psicologia , Adulto , África/etnologia , Filho de Pais com Deficiência/psicologia , Comparação Transcultural , Feminino , Humanos , Masculino , Fenótipo , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/etnologia , Risco , Esquizofrenia/diagnóstico , Esquizofrenia/etnologia , Meio Social , Reino Unido/epidemiologia , Índias Ocidentais/etnologiaRESUMO
The high rate of schizophrenia among the second-generation African-Caribbean population in Britain has prompted much concern and speculation. Sugarman and Craufurd have reported that the morbid risk in the siblings of second-generation African-Caribbean schizophrenic patients was unusually high compared with that of the siblings of white patients. METHOD: We sought to replicate these findings by comparing the morbid risk for schizophrenia in the first-degree relatives of 111 white and 73 African-Caribbean psychotic probands. The latter comprised 35 first-generation (born in the Caribbean) and 38 second-generation (born in Britain) probands. RESULTS: The morbid risk for schizophrenia was similar for the parents and siblings of white and first-generation African-Caribbean patients, and for the parents of the second-generation African-Caribbean probands. However, the siblings of second-generation African-Caribbean psychotic probands had a morbid risk for schizophrenia that was seven times that of their white counterparts (P = 0.007); similarly, the siblings of second-generation African-Caribbean schizophrenic probands had a morbid risk for schizophrenia that was four times that of their white counterparts (P = 0.05). CONCLUSIONS: These findings replicate those of the earlier report of Sugarman and Craufurd, and suggest either that the second-generation African-Caribbean population in Britain is particularly vulnerable to some environmental risk factors for schizophrenia, or that some environmental factors act selectively on this population in Britain.(AU)