Project description:A genetic study of the PRF1 gene has shown association of several polymorphisms with multiple sclerosis (MS). Haplotype analysis identified risk haplotypes strongly associated with male patients having the primary-progressive form of MS (PPMS). Gene expression microarrays were performed in 10 male PPMS patients carrying the risk (n=6) and protective haplotypes (n=4) in order to identify pathways associated with the risk haplotypes. Pathway analysis revealed overrepresentation of the cell killing gene ontology category among down-regulated genes in patients carrying risk haplotypes compared with patients carrying protective haplotypes.
Project description:Background and aimsRepresentatives from Papaver, Roemeria, Stylomecon and Meconopsis were studied to elucidate phylogenetic relationships between Papaver and these closely allied genera.MethodsTwo molecular data sets were used individually and combined and included sequences from the internally transcribed spacer region (ITS) of 18S-26S nuclear ribosomal DNA and the trnL intron and the trnL-trnF intergenic spacer region of plastid DNA.Key resultsParsimony analysis demonstrated that the genus is not monophyletic unless the closely related Roemeria, Stylomecon and Meconopsis cambrica are included in a revised circumscription of Papaver. Three distinct clades are resolved in a combined ITS and trnL-F analysis. Clade 1 consists of Papaver sect. Meconella and Asian Meconopsis. Clade 2 contains a group here identified as Papaver s.s., comprising sections Carinatae, Meconidium, Oxytona, Papaver, Pilosa, Pseudopilosa and Rhoeadium. Clade 3 consists of Papaver sect. Argemonidium and Roemeria refracta. A number of diagnostic indels support these groupings. Within clade 2, sects. Papaver and Rhoeadium are either not monophyletic or lack evidence supporting their monophyly.ConclusionsThe results of this molecular analysis indicate that a number of morphological characters such as valvate capsule dehiscence, dark or light filaments and sessile stigmatic discs have arisen in parallel. The phylogenetic trees are incongruent with the existing taxonomy of Papaver, and a revised classification is suggested.
Project description:A genetic study of the PRF1 gene has shown association of several polymorphisms with multiple sclerosis (MS). Haplotype analysis identified risk haplotypes strongly associated with male patients having the primary-progressive form of MS (PPMS). Gene expression microarrays were performed in 10 male PPMS patients carrying the risk (n=6) and protective haplotypes (n=4) in order to identify pathways associated with the risk haplotypes. Pathway analysis revealed overrepresentation of the cell killing gene ontology category among down-regulated genes in patients carrying risk haplotypes compared with patients carrying protective haplotypes. Number of samples analyzed: 10 Protective haplotype samples: UOM982, EMA1473, MMC-998, CDP1842 Risk haplotype samples: UUS1554, RAU1550, RPS1011, AGS1013, PFB1530, MGA1014
Project description:Mitochondrial DNA (mtDNA) haplotypes are associated with phenotypes and disease. To understand how mtDNA haplotypes induce these characteristics, we used four embryonic stem cell lines that have the same set of chromosomes but possess different mtDNA haplotypes. We show that mtDNA haplotypes influence changes in chromosomal gene expression and affinity for nuclear-encoded mtDNA replication factors to modulate mtDNA copy number, two events that act synchronously during differentiation. Global DNA methylation analysis showed that each haplotype induces distinct DNA methylation patterns, which, when modulated by DNA demethylation agents resulted in skewed gene expression patterns that highlight the effectiveness of the new DNA methylation patterns established by each haplotype. The haplotypes differentially regulate α-ketoglutarate, a metabolite from the TCA cycle that modulates the TET family of proteins, which catalyse the transition from 5-methylcytosine (DNA methylation) to 5-hydroxymethylcytosine (DNA demethylation). Our outcomes show a direct link between mtDNA haplotypes and DNA methylation profiles.