Project description:Schizophrenia is a severe psychiatric disease with complex etiology, affecting approximately one percent of the general population. Most genetic studies so far focused on disease association with common genetic variation such as single nucleotide polymorphisms, but recently it has become apparent that large-scale genomic copy number variants (CNVs) are involved in disease development as well. To assess the role of rare CNVs in schizophrenia, we screened 54 patients with deficit schizophrenia using Affymetrix’ GeneChip 250K SNP arrays. Keywords: genomic hybridisation
Project description:We reconstructed the Virulence Regulatory Network (VRN) of R. solanacearum strain GMI1000 by collecting bibliographical information based on genetic and genomic studies, including three transcriptomic studies. The reconstructed R. solanacearum VRN comprises 712 genes including 29 genes coding for transcription factors and 34 proteins involved in signal transduction. This VRN perceives 86 signals and controls the expression of 606 genes.
Project description:Schizophrenia is a severe psychiatric disease with complex etiology, affecting approximately one percent of the general population. Most genetic studies so far focused on disease association with common genetic variation such as single nucleotide polymorphisms, but recently it has become apparent that large-scale genomic copy number variants (CNVs) are involved in disease development as well. To assess the role of rare CNVs in schizophrenia, we screened 54 patients with deficit schizophrenia using Affymetrixâ GeneChip 250K SNP arrays. Keywords: genomic hybridisation We hybridized genomic DNA of 54 patients with deficit schizophrenia to Affymetrix' GeneChip 250K SNP (Nsp) arrays, and identified genome-wide CNV using the Copy Number Analyzer for Affymetrix GeneChip (CNAG v2.0) software, which uses a Hidden Markov Model (HMM) algorithm to calculate copy numbers.
Project description:Obesity is a major risk factor for many common diseases and has a significant heritable component. While clinical and large-scale population studies have identified several genes harbouring rare alleles with large effects on obesity risk, there are likely many unknown genes with highly penetrant effects remaining. To this end, we performed whole exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare, loss of function variants in two genes – BSN and APBA1 – with effects on BMI substantially larger than well-established obesity genes such as MC4R. One in ~6500 individuals carry a heterozygous protein truncating variant (PTV) in BSN, which confers a 6.6, 3.7 and 3-fold higher risk of severe obesity (BMI >40kg/m2), non-alcoholic fatty liver disease and type 2 diabetes, respectively. Rare PTVs in BSN were found in three patients with severe early onset obesity, but in contrast to most other obesity-related genes, rare variants in BSN and APBA1 were not associated with normal variation in childhood adiposity. Furthermore, BSN PTVs magnified the influence of common genetic variants associated with BMI, with a common polygenic score exhibiting an effect on BMI twice as large in BSN PTV carriers than non-carriers. Finally, we explored the plasma proteomic signatures of BSN PTV carriers as well as the functional consequences of BSN deletion in human iPSC-derived hypothalamic neurons. These approaches highlighted a network of differentially expressed genes that were collectively enriched for genomic regions associated with BMI, and suggest emerging roles for neurodevelopment, neurogenesis, and altered neuronal oxidative phosphorylation in the etiology of obesity.
Project description:Pineoblastoma is a rare and aggressive embryonal tumor of childhood. The molecular heterogeneity within has not been systematically evaluated. In this study, we used methylation profiling to compare the signatures of pineoblastoma and other pineal parenchymal tumors to a reference cohort of brain tumor entities (GSE90496) , clinically relevant epigenomic subgroups with characteristics genomic/transcriptomic features are described.
Project description:Porto-sinusoidal vascular disease (PSVD) is a rare vascular liver disease of unknown etiology that causes portal hypertension. It usually affects young individuals and shorts live expectancy. The deregulated pathways involved in PSVD development are unknown and therefore we lack curative treatments. The purpose of this study was to better understand the biological pathology of PSVD integrating transcriptomic and clinical data by comprehensive network-based modeling with the final aim of uncovering altered biological processes in patients with PSVD.
2022-02-11 | GSE171248 | GEO
Project description:Discovery of novel associations between known and unknown pathogenic genetic mutations and rare diseases: A Collage of Case Reports
