RESUMEN
Mitochondrial mutations are responsible for at least 1% of the cases of hereditary deafness, but the contribution of each mutation has not yet been defined in African-derived or native American genetic backgrounds. A total of 203 unselected hearing-impaired patients were screened for the presence of the mitochondrial mutation A1555G in the 12S rRNA gene and mutations in the tRNASer(UCN) gene in order to assess their frequency in the ethnically admixed Brazilian population. We found four individuals with A1555G mutation (2%), which is a frequency similar to those reported for European-derived populations in unselected samples. On the other hand, complete sequencing of the tRNASer(UCN) did not reveal reported pathogenic substitutions, namely A7445G, 7472insC, T7510C, or T7511C. Instead, other rare substitutions were found such as T1291C, A7569G, and G7444A. To evaluate the significance of these findings, 110 "European-Brazilians" and 190 "African-Brazilians" unrelated hearing controls were screened. The T1291C, A7569G and G7444A substitutions were each found in about 1% (2/190) of individuals of African ancestry, suggesting that they are probably polymorphic. Our results indicate that screening for the A1555G mutation is recommended among all Brazilian deaf patients, while testing for mutations in the tRNASer(UCN) gene should be considered only when other frequent deafness-causing mutations have been excluded or in the presence of a maternal transmission pattern.
Asunto(s)
Pérdida Auditiva/genética , Mutación/genética , ARN Ribosómico/genética , ARN de Transferencia de Serina/genética , Población Negra/genética , Brasil , Estudios de Casos y Controles , Análisis Mutacional de ADN , Femenino , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Linaje , Reacción en Cadena de la Polimerasa , ARN , ARN Mitocondrial , Índice de Severidad de la Enfermedad , Población Blanca/genéticaRESUMEN
Mitochondrial mutations are responsible for at least 1 percent of the cases of hereditary deafness, but the contribution of each mutation has not yet been defined in African-derived or native American genetic backgrounds. A total of 203 unselected hearing-impaired patients were screened for the presence of the mitochondrial mutation A1555G in the 12S rRNA gene and mutations in the tRNA Ser(UCN) gene in order to assess their frequency in the ethnically admixed Brazilian population. We found four individuals with A1555G mutation (2 percent), which is a frequency similar to those reported for European-derived populations in unselected samples. On the other hand, complete sequencing of the tRNA Ser(UCN) did not reveal reported pathogenic substitutions, namely A7445G, 7472insC, T7510C, or T7511C. Instead, other rare substitutions were found such as T1291C, A7569G, and G7444A. To evaluate the significance of these findings, 110 "European-Brazilians" and 190 "African-Brazilians" unrelated hearing controls were screened. The T1291C, A7569G and G7444A substitutions were each found in about 1 percent (2/190) of individuals of African ancestry, suggesting that they are probably polymorphic. Our results indicate that screening for the A1555G mutation is recommended among all Brazilian deaf patients, while testing for mutations in the tRNA Ser(UCN) gene should be considered only when other frequent deafness-causing mutations have been excluded or in the presence of a maternal transmission pattern.
Asunto(s)
Femenino , Humanos , Masculino , Pérdida Auditiva/genética , Mutación/genética , ARN Ribosómico/genética , ARN de Transferencia de Serina/genética , Población Negra/genética , Brasil , Estudios de Casos y Controles , Análisis Mutacional de ADN , Población Blanca/genética , Predisposición Genética a la Enfermedad , Marcadores Genéticos/genética , Linaje , Reacción en Cadena de la Polimerasa , ARN , Índice de Severidad de la EnfermedadRESUMEN
Solid tumors often consist of an admixture of cell populations with different genome constitutions. Karyotyping of this material is complicated by the low mitotic index. Even when chromosome studies are feasible, altered representation of the original cell populations after cell cultivation is possible. We report a human adrenal carcinoma that exhibited a normal karyotype after cultivation but was shown to be highly aneuploid when investigated by fluorescence in situ hybridization (FISH) in direct preparations of uncultured cells with six different centromeric probes. The high frequencies of trisomy for the investigated chromosomes in these interphase cells indicate that most of the tumor cells were in the triploid range. Strong selection for disomic cells was detected in interphase preparations after one and two subcultures and was even stronger in the corresponding metaphase preparations. Trisomy for chromosome 15 appeared to be maintained independent of triploidy and might play a role in cultured cell survival. The number of chromosome 17 centromeres was not increased in polyploid cells, suggesting loss of this chromosome in the original cells of the tumor.