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:Childhood abuse significantly increases the lifetime risk of negative mental health outcomes, including psychiatric disorders, such as depression and suicide. While clinical and epidemiological associations are well characterized, the molecular mechanisms through which adverse experiences in early life influence mental health outcomes over the lifespan remain unclear. In this study, we employed laser capture microdissection followed by RNA sequencing (LCM-seq) to investigate transcriptomic alterations to prefrontal deep-layer pyramidal neurons in individuals with a history of childhood abuse (N=24) in comparison to controls (N = 21). We first showed that LCM-seqproduced high-quality transcriptomic data that was strongly enriched for our cell type of interest (95.8% contribution). Differential expression analysis revealed119 genes that were altered between cases versus controls. Using weighted correlation network analysis (WGCNA) we next identified a network of downregulated genes, in individuals with a history of childhood abuse (r = -0.30, p = 0.04), that was enriched in pathways related to nervous system development and plasticity. The eigengene of this network was significantly correlated (r(23) = 0.490, p = 0.021) with average cell body volume of deep-layer pyramidal neurons. Of the 1042 mRNA genes within this network, 81 were differentially expressed between cases and controls. Using high-throughput qPCR, and comparing with an additional group of depressed subjects who died by suicide without a history of childhood abuse (N = 29), we found 7 genes whose expression levels were significantly (p < 0.05) predicted by a history of childhood abuse but not major depressive disorder and suicide.Our study, therefore, advances our understanding of the long term impact of childhood abuse and points to some of the molecular pathways that may underly previously observed alterations innervous system development and plasticity.
Project description:RATIONALE: Determination of genetic markers for colorectal cancer may help doctors to identify patients who are at risk.
PURPOSE: Genetic testing study of patients and families with a history of colorectal cancer to identify patients who are at risk of developing colorectal cancer.