Project description:Congenital generalized lipodystrophy (CGL) is an autosomal recessive disorder characterized by defective adipose tissue, extreme insulin resistance, and early onset of diabetes. There are four types of congenital generalized lipodystrophy based on the causative genetic alterations. The symptoms and the degrees of disease progression are varied among all affected individuals, which might be due to unknown genetic modifiers. To identify potential predictive biomarkers associated with the disease progressions, we recruited 7 patients (cgl2_p1,cgl2_p2,cgl2_p3,cgl2_p4,cgl2_p5,cgl2_p6,cgl2_p7),as well as gender/aged-matched controls (cgl2_c1,cgl2_c2,cgl2_c3,cgl2_c4,cgl2_c5,cgl2_c6,cgl2_c7).The total RNA samples were extracted from the participants' peripheral blood mononuclear cells, followed by RNA-Seq. To find the molecular signatures that might be associated with disease progression, patients were further categorized into sub-groups based on the results of biochemical analysis and their clinical symptoms (e.g. diabetes, metabolic syndrome and metal retardation). DEGs were identified for each sub-groups of patients, and pathway analysis was performed to explore the underlying dysregulated mechanisms.
Project description:mRNA-seq read files of peripheral blood mononuclear cells from congenital generalized lipodystrophy patients and their gender/aged-matched controls
Project description:Lipodystrophies resemble syndromes of disturbed adipocyte biology or development and severe congenital forms (CGL) lack adipose tissue. The ubiquitous immediate-early gene c-fos is one essential transcription factor to initiate adipocyte differentiation. In a CGL patient we identified a single homozygous point mutation in the promoter of c-fos gene. The mutation facilitates the formation of a novel specific protein/ DNA complex and ubiquitously reduces basal and inducible c-fos transcription activity. We used microarrays to determine differences in gene expression due to a repressive c-fos promoter mutation in a patient with CGL. Cultued fibroblasts of non diabetic controls and a patient with c-fos promoter mutation were analyzed at identical passage number and growth conditions without further additional treatment.
Project description:Genome wide DNA methylation profiling of Congenital Lipodystrophy type 2 patients, mutation carriers , and healthy control samples .The Infinium MethylationEPIC Kit was used to measure genome-wide DNA methylation across > 868,000 CpG sites.
Project description:Lipodystrophies resemble syndromes of disturbed adipocyte biology or development and severe congenital forms (CGL) lack adipose tissue. The ubiquitous immediate-early gene c-fos is one essential transcription factor to initiate adipocyte differentiation. In a CGL patient we identified a single homozygous point mutation in the promoter of c-fos gene. The mutation facilitates the formation of a novel specific protein/ DNA complex and ubiquitously reduces basal and inducible c-fos transcription activity. We used microarrays to determine differences in gene expression due to a repressive c-fos promoter mutation in a patient with CGL.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
