Project description:Present day Roma genome were shaped by the extensive inbreeding and admixture during their Diaspora. Here, we shed light on the Roma demographic history by analyzing the whole genome sequence of 46 Roma individuals pertaining to four migrant groups in six European countries. The strong reduction in effective population size (~44%), that occurred around 2kya, was not masked by the subsequent high admixture in Middle Eastern and European countries.
Project description:The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We provide a bioinformatic analysis of copy number variation and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We individually examined the copy number variation and DNA methylation for 44 primary ovarian cancer samples and 7 ovarian normal samples using our MOMA-ROMA technology and Affymetrix expression data as well as 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with significantly altered copy number and correlated changes in expression. We identify changes in DNA methylation and expression for all amplified and deleted genes. We predicted 615 potential oncogenes and tumor suppressors candidates by integrating these multiple genomic and epigenetic data types. This ROMA experiment was performed on Ovarian Tumor samples using the same platform as previously reported by Navin, N. et. al. Genome Res. 2010 Jan;20(1):68-80 (PMID: 19903760). Analysis of the array data was performed as previously reported in Chen, S. et. al. Cancer Biol Ther. 2008 Nov;7(11):1793-802. (PMID: 18836286 ).
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.
Project description:The Roma people are the largest transnational ethnic minority in Europe and can be considered the last human migration of South Asian origin into the continent. They departed Northwest India approximately 1,000 years ago, reaching the Balkan Peninsula around the 12th century and Romania in the 14th century. Here, we generated whole-genome sequencing data of Roma (Romani/Rroma) and non-Roma (European/Romanian) individuals from Romania. We performed a genome-wide scan of selection comparing the Roma, their local host population (Romanians), and a Northwestern Indian population to identify the selective pressures faced by the Roma when they settled in Europe.
Project description:The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to identify genes critical to the development and progression of cancer. We provide a bioinformatic analysis of copy number variation and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We individually examined the copy number variation and DNA methylation for 44 primary ovarian cancer samples and 7 ovarian normal samples using our MOMA-ROMA technology and Affymetrix expression data as well as 379 tumor samples analyzed by The Cancer Genome Atlas. We have identified 346 genes with significant deletions or amplifications among the tumor samples. Utilizing associated gene expression data we predict 156 genes with significantly altered copy number and correlated changes in expression. We identify changes in DNA methylation and expression for all amplified and deleted genes. We predicted 615 potential oncogenes and tumor suppressors candidates by integrating these multiple genomic and epigenetic data types. This ROMA experiment was performed on Ovarian Tumor samples using the same platform as previously reported by Navin, N. et. al. Genome Res. 2010 Jan;20(1):68-80 (PMID: 19903760). Analysis of the array data was performed as previously reported in Chen, S. et. al. Cancer Biol Ther. 2008 Nov;7(11):1793-802. (PMID: 18836286 ). The genomic DNA from each tumor was labeled with Cy5 and hybridized to an 85K Bgl2 ROMA Microarray. A normal reference male fibroblast was labeled with Cy3 as a control. The value data repesents a log ratio. (As previously reported Chen, S. et. al. Cancer Biol Ther. 2008 Nov;7(11):1793-802. PMID: 18836286 ).
Project description:Modern genetic data combined with appropriate statistical methods have the potential to contribute substantially to our understanding of human history. We have developed an approach that exploits the genomic structure of admixed populations to date and characterize historical mixture events at fine scales. We used this to produce an atlas of worldwide human admixture history, constructed using genetic data alone and encompassing over 100 events occurring over the past 4,000 years. We identify events whose dates and participants suggest they describe genetic impacts of the Mongol Empire, Arab slave trade, Bantu expansion, first millennium CE migrations in eastern Europe, and European colonialism, as well as unrecorded events, revealing admixture to be an almost universal force shaping human populations.
Project description:Modern genetic data combined with appropriate statistical methods have the potential to contribute substantially to our understanding of human history. We have developed an approach that exploits the genomic structure of admixed populations to date and characterize historical mixture events at fine scales. We used this to produce an atlas of worldwide human admixture history, constructed using genetic data alone and encompassing over 100 events occurring over the past 4,000 years. We identify events whose dates and participants suggest they describe genetic impacts of the Mongol Empire, Arab slave trade, Bantu expansion, first millennium CE migrations in eastern Europe, and European colonialism, as well as unrecorded events, revealing admixture to be an almost universal force shaping human populations. 158 indviduals of Eurasian descent included as part of a global analysis of admixture
Project description:Generating mammalian cells with desired mtDNA sequences is enabling for studies of mitochondria, disease modeling, and potential regenerative therapies. MitoPunch, a high-throughput mitochondrial transfer device, produces cells with specific mtDNA-nDNA combinations by transferring isolated mitochondria from mouse or human cells into primary or immortal mtDNA-deficient (p0) cells. Stable isolated mitochondrial recipient (SIMR) cells isolated in restrictive media permanently retain donor mtDNA and reacquire respiration. However, SIMR fibroblasts maintain a p0-like cell metabolome and transcriptome despite growth in restrictive media. We reprogram non-immortal SIMR fibroblasts into induced pluripotent stem cells (iPSCs) with subsequent differentiation into diverse functional cell types, including mesenchymal stem cells (MSCs), adipocytes, osteoblasts, and chondrocytes. Remarkably, following reprogramming and differentiation, SIMR fibroblasts molecularly and phenotypically resemble un-manipulated control fibroblasts carried through the same protocol. Thus, our MitoPunch ‘pipeline’ enables the production of SIMR cells with unique mtDNA-nDNA combinations for additional studies and applications in multiple cell types.