Project description:A population and admixture analysis of Mesoamerican Totonacs and South American Bolivians. A panel of highly informative ancestry informative markers (AIMs) for New World populations is identified. Regions coinciding with AIMs are have moderate signatures of selection. Population structure and differentiation were assessed with a genome-wide panel of 815,377 autosomal markers, Y-chromosome STR and SNPs, and mtDNA sequence data.
Project description:This SuperSeries is composed of the following subset Series: GSE23384: Gene profiling using archival formalin-fixed paraffin-embedded breast cancer specimens can generate informative microarray data: A comparison with matched fresh fine needle aspiration biopsy samples (FFPE samples) GSE23385: Gene profiling using archival formalin-fixed paraffin-embedded breast cancer specimens can generate informative microarray data: A comparison with matched fresh fine needle aspiration biopsy samples (FNA samples) Refer to individual Series
Project description:There is increasing evidence that interindividual epigenetic variation is an etiological factor in common human diseases. Such epigenetic variation could be genetic or non-genetic in origin, and epigenome-wide association studies (EWASs) are underway for a wide variety of diseases/phenotypes. However, performing an EWAS is associated with a range of issues not typically encountered in genome-wide association studies (GWASs), such as the tissue to be analyzed. In many EWASs, it is not possible to analyze the target tissue in large numbers of live humans, and consequently surrogate tissues are employed, most commonly blood. But there is as yet no evidence demonstrating that blood is more informative than buccal cells, the other easily accessible tissue. To assess the potential of buccal cells for use in EWASs, we performed a comprehensive analysis of a buccal cell methylome using whole-genome bisulfite sequencing. Strikingly, a buccal vs. blood comparison reveals >6X as many hypomethylated regions in buccal. These tissue-specific differentially methylated regions (tDMRs) are strongly enriched for DNaseI hotspots. Almost 75% of these tDMRs are not captured by commonly used DNA methylome profiling platforms such as Reduced Representational Bisulfite Sequencing and the Illumina Infinium HumanMethylation450 BeadChip, and they also display distinct genomic properties. Buccal hypo-tDMRs show a statistically significant enrichment near SNPs associated to disease identified through GWASs. Finally, we find that, compared with blood, buccal hypo-tDMRs show significantly greater overlap with hypomethylated regions in other tissues. We propose that for non-blood based diseases/phenotypes, buccal will be a more informative tissue for EWASs. Buccal Profile generated from 14 Buccal Individuals
Project description:STAT5 functions in human inflammatory monocytes is largely unknown. We identified the anti-inflammatory function of CD127-STAT5 axis in human monocytes. To investigate the mechanism underlying STAT5-mediated anti-inflammatory regulation, thoroughly dissecting the STAT5 genomic distribution in human monocytes would be informative. Therefore, we performed anti-STAT5 ChIP-seq analyses for CD127high monocytes under LPS stimulation to globally characterize the STAT5 occupancy in CD127 expressing human monocytes.
Project description:Pathology archives contain vast resources of clinical material in the form of formalin-fixed paraffin embedded (FFPE) tissue samples. Due to the methods of tissue fixation and storage, the integrity of DNA and RNA available from FFPE tissue is compromised, meaning obtaining informative data regarding epigenetic, genomic and expression alterations can be challenging. Here we have investigated the utility of repairing damaged DNA derived from FFPE tumours prior to single nucleotide polymorphism (SNP) arrays for whole genome DNA copy number analysis.
Project description:The frequent occurrence of persistent or relapsed disease following induction chemotherapy in AML necessitates a better understanding of the clonal relationship of AML in various disease phases. In this study, we employed SNP 6.0 array-based genomic profiling of acquired copy number aberrations (aCNA) and copy neutral LOH (cnLOH) together with sequence analysis of recurrently mutated genes to characterize paired AML genomes. We analyzed 28 AML sample pairs from patients that achieved complete remission with chemotherapy and subsequently relapsed and 11 sample pairs from patients with persistent disease following induction chemotherapy. Through review of aCNA/cnLOH and gene mutation profiles in informative cases we demonstrate that relapsed AML invariably represents reemergence or evolution of a founder clone. Furthermore, all individual aCNA or cnLOH detected at presentation persisted at relapse indicating that this lesion type is proximally involved in AML evolution. Analysis of informative paired persistent AML disease samples uncovered cases with two coexisting dominant clones of which at least one was chemotherapy sensitive and one resistant, respectively. These data support the conclusion that incomplete eradication of AML founder clones rather than stochastic emergence of fully unrelated novel clones underlies AML relapse and persistence with direct implications for clinical AML research