tailieunhanh - báo cáo khoa học: " Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders by microRNA expression profiling of lymphoblastoid cell lines"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders by microRNA expression profiling of lymphoblastoid cell lines | Sarachana et al. Genome Medicine 2010 2 23 http content 2 4 23 w Genome Medicine RESEARCH Open Access Investigation of post-transcriptional gene regulatory networks associated with autism spectrum disorders by microRNA expression profiling of lymphoblastoid cell lines Tewarit Sarachana1 Rulun Zhou2 Guang Chen2 Husseini K Manji2 and Valerie W Hu1 Abstract Background Autism spectrum disorders ASD are neurodevelopmental disorders characterized by abnormalities in reciprocal social interactions and language development and or usage and by restricted interests and repetitive behaviors. Differential gene expression of neurologically relevant genes in lymphoblastoid cell lines from monozygotic twins discordant in diagnosis or severity of autism suggested that epigenetic factors such as DNA methylation or microRNAs miRNAs may be involved in ASD. Methods Global miRNA expression profiling using lymphoblasts derived from these autistic twins and unaffected sibling controls was therefore performed using high-throughput miRNA microarray analysis. Selected differentially expressed miRNAs were confirmed by quantitative reverse transcription-polymerase chain reaction qRT-PCR analysis and the putative target genes of two of the confirmed miRNA were validated by knockdown and overexpression of the respective miRNAs. Results Differentially expressed miRNAs were found to target genes highly involved in neurological functions and disorders in addition to genes involved in gastrointestinal diseases circadian rhythm signaling as well as steroid hormone metabolism and receptor signaling. Novel network analyses of the putative target genes that were inversely expressed relative to the relevant miRNA in these same samples further revealed an association with ASD and other co-morbid disorders including muscle and gastrointestinal diseases as well as with biological functions implicated in ASD such as memory and synaptic plasticity. Putative gene targets ID3 and PLK2 of two