ABSTRACT: Patients with autoimmune disorders exhibit highly reproducible gene expression profiles in their peripheral blood mononuclear cells. These signatures may result from chronic inflammation, other disease manifestations, or may reflect family resemblance. To test the latter hypothesis, we determined gene expression profiles in unaffected first-degree relatives of individuals with autoimmune disease. Gene expression profiles in unaffected first-degree relatives resembled the profiles found in individuals with autoimmune diseases. A high percentage of differentially expressed genes in unaffected first-degree relatives were previously identified as autoimmune signature genes. Examination of the linear regression relationship of gene transcript levels between parent-offspring pairs revealed that autoimmune signature genes display high levels of family resemblance. Taken together, these results support the hypothesis that these variations in gene transcript levels are associated with family resemblance rather than clinical manifestations of disease. Gene expression profiling of autoimmune families
Project description:Patients with autoimmune disorders exhibit highly reproducible gene expression profiles in their peripheral blood mononuclear cells. These signatures may result from chronic inflammation, other disease manifestations, or may reflect family resemblance. To test the latter hypothesis, we determined gene expression profiles in unaffected first-degree relatives of individuals with autoimmune disease. Gene expression profiles in unaffected first-degree relatives resembled the profiles found in individuals with autoimmune diseases. A high percentage of differentially expressed genes in unaffected first-degree relatives were previously identified as autoimmune signature genes. Examination of the linear regression relationship of gene transcript levels between parent-offspring pairs revealed that autoimmune signature genes display high levels of family resemblance. Taken together, these results support the hypothesis that these variations in gene transcript levels are associated with family resemblance rather than clinical manifestations of disease. Keywords: Gene expression profiling
Project description:Even though autoimmune diseases are heterogeneous, believed to result from the interaction between genetic and environmental components, patients with these disorders exhibit reproducible patterns of gene expression in their peripheral blood mononuclear cells. A portion of this gene expression profile reflects family resemblance rather than the actual presence of an autoimmune disease. Here we wanted to identify that portion of this gene expression pattern that is independent of family resemblance and determine if it is a product of disease duration, disease onset, or other factors. By increasing the number of autoimmune samples in our analysis and employing supervised clustering algorithms, we identified 100 genes whose expression profiles are shared in individuals with various autoimmune diseases but are not shared by first-degree relatives of individuals with autoimmune disease or by controls. Individuals with early disease (1 yr after onset) and established disease (10 yr after onset) exhibit a near identical expression pattern suggesting that this unique profile reflects disease onset rather than disease duration. supervised gene expression profiling were performed to a cohort sample pool: control individuals(8), unaffected family members of autoimmune diseases patients (8), and individuals with autoimmune diseases (54). we try to identify a gene expression signatures that were exclusively associated with autoimmune diseases but not infulenced by genetic components
Project description:Even though autoimmune diseases are heterogeneous, believed to result from the interaction between genetic and environmental components, patients with these disorders exhibit reproducible patterns of gene expression in their peripheral blood mononuclear cells. A portion of this gene expression profile reflects family resemblance rather than the actual presence of an autoimmune disease. Here we wanted to identify that portion of this gene expression pattern that is independent of family resemblance and determine if it is a product of disease duration, disease onset, or other factors. By increasing the number of autoimmune samples in our analysis and employing supervised clustering algorithms, we identified 100 genes whose expression profiles are shared in individuals with various autoimmune diseases but are not shared by first-degree relatives of individuals with autoimmune disease or by controls. Individuals with early disease (1 yr after onset) and established disease (10 yr after onset) exhibit a near identical expression pattern suggesting that this unique profile reflects disease onset rather than disease duration. Keywords: gene expression signatures
Project description:Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD) is caused by mutations in the Valosin Containing Protein (VCP) gene on chromosome 9p12-13. To elucidate affected signaling transduction axes in IBMPFD, we determined expression profiles using microarray technology in quadriceps muscle from patients and unaffected relatives. Muscle from 10 individuals (7 affected, 3 unaffected first degree relatives) was obtained after informed consent for the muscle biopsy was obtained.
Project description:Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by contractions of repetitive elements within the macrosatellite D4Z4 on chromosome 4q35. In order to develop mRNA-based biomarkers of affected muscles, we used GeneChip Gene 1.0 ST arrays for global analysis of gene expression in muscle biopsy specimens obtained from FSHD subjects and their unaffected first degree relatives. FSHD typically affects biceps muscles more severely than deltoid muscles. To examine muscle-specific expression changes associated with FSHD while controlling for background genetic variation, we analyzed RNA extracted from both biceps and deltoids of FSHD subjects and unaffected first-degree relatives.
Project description:Transcription profiling by array of human skeletal muscle from patients with type 2 diabetes, their first degree relatives and healthy unrelated controls
Project description:Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by contractions of repetitive elements within the macrosatellite D4Z4 on chromosome 4q35. In order to develop mRNA-based biomarkers of affected muscles, we used GeneChip Gene 1.0 ST arrays for global analysis of gene expression in muscle biopsy specimens obtained from FSHD subjects and their unaffected first degree relatives.
Project description:We determined the expression profiles in skeletal muscle from people with type 2 diabetes, first degree relatives, and healthy control individuals by microarray experiments. All subjects were Caucasian males and biopsies were taken after a controlled metabolic period of a two hour hyperinsulinemic euglycemic clamp. Our results show for the first time that insulin signaling is significantly downregulated in people with type 2 diabetes, whereas it is significantly upregulated in first degree relatives. Furthermore, we identify several new genes in skeletal muscle from first degree relatives that have an altered gene expression compared to healthy controls.
Project description:Type 1 Diabetes (T1D) is considered to be a Th1 autoimmune disease characterised by an absolute lack of insulin caused by an autoimmune destruction of the insulin producing pancreatic beta cells. Th1 lymphocytes are responsible for the infiltration of the islets of Langerhans and for the cytokine release that supports cytotoxic (Tc) lymphocytes to mediate destruction of the beta cells. The preclinical disease stage is characterized by the generation of the self-reactive lymphocytes that infiltrate the pancreas and selectively destroy the insulin-producing beta cells present in the islets. Other cellular immune mechanisms regarding immunoregulation and antigen presentation and processing are involved in T1D pathogenesis as well. Our aim was to identify genes involved in the corresponding signalling cascades, especially those which may serve as promising diagnostic tools for the identification of persons in the prediabetic phase of the disease. We addressed the question by analysing gene expression profiles of freshly isolated peripheral blood mononuclear cells in type 1 diabetes patients, their first degree relatives divided according to their autoantibody status, and healthy controls. 9 T1D-patients versus 10 first degree relatives versus 10 healthy controls