RESUMEN
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare, autosomal recessive disorder associated with mutations in the thymidine phosphorylase (TYMP) gene. The main objective of this study was to characterize the genetic profiles of the deceased proband's family members (N = 4) using DNA sequencing and to determine miRNA deregulation in MNGIE using miRNA microarray profiling and bioinformatic analysis. We found that the genetic profile of the younger sister showed similar TYMP gene mutations as that of the proband with the exception of a heterozygous mutation in exon 10. The miRNA microarray revealed 55 significantly up-regulated and 65 significantly down-regulated miRNAs. These miRNAs have been implicated in various mitochondrial dynamics such as energy metabolism, Krebs cycle, mitochondria-associated apoptosis, and mitophagy. In conclusion, we demonstrate that blood miRNAs are deregulated in the pathogenesis of MNGIE and these changes may have therapeutic implications. Further experimental studies will be required to elucidate the functional miRNA-mRNA interactions in MNGIE.
Asunto(s)
MicroARNs/genética , Encefalomiopatías Mitocondriales/genética , Transcriptoma , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Análisis por Conglomerados , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Malasia , Masculino , Persona de Mediana Edad , Encefalomiopatías Mitocondriales/diagnóstico , Mutación , Linaje , Timidina Fosforilasa/genética , Adulto JovenRESUMEN
The papaya (Carica papaya L.) is one of the most important economic tropical fruits in the world, and the hermaphrodite is the preferred type in field cultures. We analyzed the sexual ratio of offspring from the cultivar 'Taiwan Seed Station No. 7' (T7) by a self-cross and its cross with Taichung Sunrise (TS). Female progeny from the T7 self-crossing were not observed. This finding may be caused by a lethal gene that is linked to females. In this study, we selected 192 simple sequence repeats (SSRs) to analyze the polymorphism between T7 and TS. A total of 37 SSRs were identified for T7 and TS. In addition, 14 SSRs served as the molecular makers for identification of T7, TS and their hybrid offsprings. Thus, the results show that the genetic similarity between T7 and TS is rather high. This suggests that T7 may be a mutant of TS. Phylogenetic analysis from the SSR polymorphisms of the above parent strains and 15 F1 offspring revealed the genetic distance of the F1 offspring located between T7 and TS. The results of this study may provide an opportunity for elucidating the genetic characteristics of all hermaphrodites via identification of molecular makers.
Asunto(s)
Carica/genética , Organismos Hermafroditas/genética , Repeticiones de Microsatélite , Polimorfismo Genético , Genes Letales , Marcadores Genéticos , Genoma de Planta , SexoRESUMEN
Cerebral ischemia or ischemic stroke is mainly attributed to vascular and circulation disorders. Among protein biomarkers, RNA profiles have also been identified as markers of ischemic stroke. MicroRNA-145 expression is ostensibly recognized as marker and modulator of vascular smooth muscle cell phenotype; however, expression levels in ischemic stroke had not been investigated. Employing real-time quantitative PCR, we examined the expression profile of circulatory microRNA-145 in healthy control subjects (N = 14) and ischemic stroke patients (N = 32). Circulatory microRNA-145 expression was significantly higher in ischemic stroke patients than in control subjects. This demonstrates that hemostatic mechanisms are affected by ischemic stroke. We conclude that circulating microRNA-145 has potential as a biomarker for ischemic stroke.