Assuntos
Adenosina Trifosfatases/genética , Códon sem Sentido , Paraplegia/genética , Linhagem , Adulto , Cromossomos Humanos Par 2 , Análise Mutacional de DNA/métodos , Éxons , Feminino , Alemanha/epidemiologia , Humanos , Leucina/genética , Masculino , Pessoa de Meia-Idade , Paraplegia/epidemiologia , EspastinaAssuntos
Ataxia/genética , Síndrome do Cromossomo X Frágil/genética , Proteínas do Tecido Nervoso/genética , Proteínas de Ligação a RNA/genética , Idoso , Ataxia/fisiopatologia , Feminino , Proteína do X Frágil da Deficiência Intelectual , Síndrome do Cromossomo X Frágil/fisiopatologia , Humanos , Masculino , Repetições de Trinucleotídeos/genéticaAssuntos
Mapeamento Cromossômico , Ligação Genética/genética , Marcadores Genéticos/genética , Transtornos da Motilidade Ocular/genética , Esquizofrenia/genética , Alelos , Cromossomos Humanos Par 6/genética , Saúde da Família , Frequência do Gene , Predisposição Genética para Doença/genética , Humanos , Modelos Genéticos , Transtornos da Motilidade Ocular/fisiopatologia , Penetrância , Prevalência , Acompanhamento Ocular Uniforme/fisiologia , Estatísticas não ParamétricasRESUMO
Recently, case-control studies have suggested an association between the polymorphic CAG repeat in the neuronal potassium channel gene hSKCa3 and an increased susceptibility to schizophrenia, with larger repeats being overrepresented in schizophrenic patients. Therefore, we have examined the CAG repeat polymorphism in hSKCa3 and four adjacent microsatellite markers in 12 multiplex schizophrenia families. On performing the extended transmission/disequilibrium test (ETDT), neither allele-wise (P = 0.67) nor genotype-wise (P = 0.071) analysis yielded evidence to support linkage disequilibrium between schizophrenia and the hSKCa3 CAG repeat alleles. No significant results were produced performing parametric and non-parametric linkage analysis between schizophrenia and hSKCa3, as well as the four microsatellite markers. Thus, our study does not support the involvement of hSKCa3 in schizophrenia. Furthermore, we refined the physical localization on chromosome 1q21.3 using linkage analysis. No recombination was seen between markers D1S2624 and D1S1600 and the polymorphic CAG repeat in hSKCa3. LOD scores of 19.44 and 12.97, respectively, were obtained at a recombination fraction of 0.00.
Assuntos
Cromossomos Humanos Par 1 , Neuropeptídeos/genética , Polimorfismo Genético , Canais de Potássio/genética , Esquizofrenia/genética , Repetições de Trinucleotídeos , Mapeamento Cromossômico , DNA/sangue , Marcadores Genéticos , Predisposição Genética para Doença/genética , Genótipo , Humanos , Desequilíbrio de Ligação , Escore Lod , Recombinação Genética , Canais de Potássio Ativados por Cálcio de Condutância BaixaRESUMO
The main mutation causing Friedreich ataxia (FRDA) is the expansion of a GAA repeat localized within the intron between exon 1 and exon 2 of the gene X25. This expansion has been observed in 98% of FRDA chromosomes. To analyze frequencies of markers tightly linked to the Friedreich ataxia gene and to investigate wheter a limited number of ancestral chromosomes are shared by German FRDA families, a detailed analysis employing nine polymorphic markers was performed. We found strong linkage disequilibria and association of FRDA expansions with a few haplotypes. FRDA haplotypes differ significantly from control haplotypes. Our results confirm that GAA repeat expansions in intron 1 of the frataxin gene are limited to a few chromosomes and indicate an obvious founder effect in German patients. Based on these analyses, we estimate a minimum age of the mutation of 107 generations.
Assuntos
Ataxia de Friedreich/genética , Proteínas de Ligação ao Ferro , Desequilíbrio de Ligação , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Evolução Molecular , Alemanha , Haplótipos , Humanos , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA , Expansão das Repetições de Trinucleotídeos , FrataxinaRESUMO
The difficulties in defining the borders of the schizophrenia spectrum is one major source of variance in linkage studies of schizophrenia. The employment of biological markers may prove advantageous. Due to empirical evidence, eye tracking dysfunction (ETD) has been discussed to be the most promising marker for genetic liability to schizophrenia. With respect to the recent progress in genomic scans, which have pointed to the short arm of chromosome 6, we carried out a scan of the 6p21-23 region with 16 microsatellite markers to test for linkage between chromosomal markers and ETD as well as schizophrenia. We tested 5 models of inheritance of ETD and found maximum two-point lod scores of 3.51 for D6S271 and 3.44 for D6S282. By including these markers in a multipoint analysis, a lod score of 4.02 was obtained. In the case of schizophrenia, 7 models were tested; however, with non-significant results. Our findings, together with another recent linkage report, point to the possibility of a second susceptibility locus for schizophrenia which may be located centromeric to the HLA region. Also, the evidence of ETD being a susceptibility marker for schizophrenia receives further support.
Assuntos
Cromossomos Humanos Par 6 , Transtornos da Motilidade Ocular/complicações , Esquizofrenia/genética , Adulto , Idoso , Biomarcadores , Ligação Genética , Humanos , Raios Infravermelhos , Pessoa de Meia-Idade , Linhagem , Esquizofrenia/complicações , Esquizofrenia/diagnósticoRESUMO
Four polymorphic sites of the short arm of the X chromosome were studied in two racial groups from India, the Assamese and the Malayalee. Since the allelic frequencies of the two groups did not differ markedly from each other, the data from the two populations were pooled. The frequency of the A2 allele was 0.57 for the L1.28 probe, 0.20 for the RC8 probe, 0.28 for the pD2 probe and 0.11 for the L754 probe. The A3 allelic fragment of the RC8 probe was not found among 67 Indians, and in one Assamese woman an additional 7.0-kilobase fragment was found. The differences between the Indian population and other ethnic groups were analyzed.