RESUMEN
BACKGROUND: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer-specific survival. METHODS: We conducted a large meta-analysis of studies in populations of European ancestry, including 37954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200000 and 900000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)-negative patients (920 events) and 23059 ER-positive patients (1333 events). All statistical tests were two-sided. RESULTS: We identified one new locus (rs2059614 at 11q24.2) associated with survival in ER-negative breast cancer cases (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.55 to 2.47, P = 1.91 x 10(-8)). Genotyping a subset of 2113 case patients, of which 300 were ER negative, provided supporting evidence for the quality of the imputation. The association in this set of case patients was stronger for the observed genotypes than for the imputed genotypes. A second locus (rs148760487 at 2q24.2) was associated at genome-wide statistical significance in initial analyses; the association was similar in ER-positive and ER-negative case patients. Here the results of genotyping suggested that the finding was less robust. CONCLUSIONS: This is currently the largest study investigating genetic variation associated with breast cancer survival. Our results have potential clinical implications, as they confirm that germline genotype can provide prognostic information in addition to standard tumor prognostic factors.
Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Polimorfismo de Nucleótido Simple , Neoplasias de la Mama/química , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Pronóstico , Receptores de Estrógenos/análisis , Análisis de Supervivencia , Población Blanca/genéticaRESUMEN
OBJECTIVES: Our study aimed to investigate the impact of fatigue on the severity of stroke and to explore the underlying mechanisms. METHODS: Fatigued male rats underwent middle cerebral artery occlusion and the infarcted brain area was determined. Then, coagulation parameters were assessed in the fatigued group and a control group. In addition, the level of fibrinogen was determined in rats deprived of sleep for various numbers of days. To study whether interleukin-6 was involved in fibrinogen synthesis during fatigue, we also measured levels of interleukin-6 in rats deprived of sleep for various numbers of days. Furthermore, brain injury by middle cerebral artery occlusion was measured in wild-type mice, interleukin-6-/- mice and wild-type mice treated with bezafibrate. RESULTS: More severe cerebral infarction was observed in the fatigued rats, resulting in an infarct ratio of 23.4%. The infarct ratio was significantly increased in the fatigued rats compared with that in the control group (8%, p<0.05). The level of fibrinogen was increased significantly in the fatigued rats compared with that in the control group. In addition, a marked reduction in fibrinogen level was observed in the fatigued interleukin-6-/- mice compared to their wild-type counterparts, whereas no difference was observed between fatigued wild-type mice and interleukin-6-/- rats treated with recombinant human interleukin-6. The reduction in brain injury due to middle cerebral artery occlusion during fatigue was observed in interleukin-6-/- mice and wild-type mice treated with bezafibrate. CONCLUSION: Fatigue could increase stroke severity and was associated with the interleukin-6-induced expression of fibrinogen.
Asunto(s)
Infarto Cerebral/sangre , Fatiga/sangre , Fibrinógeno/biosíntesis , Interleucina-6/sangre , Animales , Biomarcadores/sangre , Infarto Cerebral/etiología , Modelos Animales de Enfermedad , Fatiga/complicaciones , Masculino , Ratones , Ratas Sprague-Dawley , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: Our study aimed to investigate the impact of fatigue on the severity of stroke and to explore the underlying mechanisms. METHODS: Fatigued male rats underwent middle cerebral artery occlusion and the infarcted brain area was determined. Then, coagulation parameters were assessed in the fatigued group and a control group. In addition, the level of fibrinogen was determined in rats deprived of sleep for various numbers of days. To study whether interleukin-6 was involved in fibrinogen synthesis during fatigue, we also measured levels of interleukin-6 in rats deprived of sleep for various numbers of days. Furthermore, brain injury by middle cerebral artery occlusion was measured in wild-type mice, interleukin-6-/- mice and wild-type mice treated with bezafibrate. RESULTS: More severe cerebral infarction was observed in the fatigued rats, resulting in an infarct ratio of 23.4%. The infarct ratio was significantly increased in the fatigued rats compared with that in the control group (8%, p<0.05). The level of fibrinogen was increased significantly in the fatigued rats compared with that in the control group. In addition, a marked reduction in fibrinogen level was observed in the fatigued interleukin-6-/- mice compared to their wild-type counterparts, whereas no difference was observed between fatigued wild-type mice and interleukin-6-/- rats treated with recombinant human interleukin-6. The reduction in brain injury due to middle cerebral artery occlusion during fatigue was observed in interleukin-6-/- mice and wild-type mice treated with bezafibrate. CONCLUSION: Fatigue could increase stroke severity and was associated with the interleukin-6-induced expression of fibrinogen. .
Asunto(s)
Animales , Masculino , Ratones , Infarto Cerebral/sangre , Fatiga/sangre , Fibrinógeno/biosíntesis , /sangre , Biomarcadores/sangre , Infarto Cerebral/etiología , Modelos Animales de Enfermedad , Fatiga/complicaciones , Ratas Sprague-Dawley , Índice de Severidad de la EnfermedadRESUMEN
Microsatellites, or simple sequence repeats (SSRs), in expressed sequence tags (ESTs) provide an opportunity for low cost SSR development. We looked for EST-SSRs in 403,511 ESTs (generated by 454 sequencing and representing 70,654 contigs and 52,082 singletons) from soybean globular stage embryos. Among 122,736 unique ESTs, 3,729 contained one or more SSRs. In total, 3,989 SSRs were identified including 304 mono, 1,374 di, 2,208 tri, 70 tetra, 13 penta and 20 hexanucleotide SSRs. Thirty three EST-SSRs were selected for primer design and polymorphism analysis using twenty soybean cultivars and one wild-type soybean. Successful amplification was obtained using 21 of these primer pairs, 11 of which detected polymorphisms in these soybean cultivars. These results demonstrated that 454 high throughput sequencing is a powerful tool for molecular marker development. From the 3,989 identified SSRs we expect to obtain a large number of makers with polymorphism among different soybean cultivars, which would be useful for analysis of genetic diversity and maker assisted selection in the soybean breeding programs.
Asunto(s)
Etiquetas de Secuencia Expresada , Glycine max/genética , Genes de Plantas , Marcadores Genéticos , Repeticiones de Microsatélite , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Análisis de Secuencia de ADNRESUMEN
Making use of the gene resources of wild type peanuts is a way to increase the genetic diversity of the cultivars. Marker assisted selection (MAS) could shorten the process of inter-specific hybridization and provide a possible way to remove the undesirable traits. However, the limited number of molecular markers available in peanut retarded its MAS process. We started a peanut ESTs (Expressed Sequence Tags) project aiming at cloning genes with agronomic importance and developing molecular markers. In this study we found 610 ESTs that contained one or more SSRs from 12,000 peanut ESTs. The most abundant SSRs in peanut are trinucleotides (66.3 percent) SSRs and followed by dinucleotide (28.8 percent) SSRs. AG/TC (10.7 percent) repeat was the most abundant and followed by CT/GA (9.0 percent), CTT/GAA (7.4 percent), and AAG/TTC (7.3 percent) repeats. Ninety-four SSR containing ESTs were randomly selected for primer design and synthesis, of which 33 pairs could generate good amplification and were used for polymorphism assessment. Results showed that polymorphism was very low in cultivars, while high level of polymorphism was revealed in wild type peanuts.