A systems genetics study of swine illustrates mechanisms underlying human phenotypic traits

BACKGROUND: The pig, which shares greater similarities with human than with mouse, is important for agriculture and for studying human diseases. However, similarities in the genetic architecture and molecular regulations underlying phenotypic variations in humans and swine have not been systematically assessed. RESULTS: We systematically surveyed ~500 F2 pigs genetically and phenotypically. By comparing candidates for anemia traits identified in swine genome-wide SNP association and human genome-wide association studies (GWAS), we showed that both sets of candidates are related to the biological process “cellular lipid metabolism” in liver. Human height is a complex heritable trait; by integrating genome-wide SNP data and human adipose Bayesian causal network, which closely represents bone transcriptional regulations, we identified PLAG1 as a causal gene for limb bone length. This finding is consistent with GWAS findings for human height and supports the common genetic architecture between swine and humans. By leveraging a human protein-protein interaction network, we identified two putative candidate causal genes TGFB3 and DAB2IP and the known regulators MESP1 and MESP2 as responsible for the variation in rib number and identified the potential underlying molecular mechanisms. In mice, knockout of Tgfb3 and Tgfb2 together decreases rib number. CONCLUSION: Our findings show that integrative network analyses reveal causal regulators underlying the genetic association of complex traits in swine and that these causal regulators have similar effects in humans. Thus, swine are a potentially good animal model for studying some complex human traits that are not under intense selection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1240-y) contains supplementary material, which is available to authorized users

The last three millions of unequal spring thaws

Evidence from various climate proxies provides us with increasingly reliable proof that only in the past 10 millennia were natural systems more or less as we see them at the present (without considering human impact). Prior to 10,000 years ago, natural systems repeatedly changed under the influence of an unstable climate. This is particularly true over the last one million years. During these times, terrestrial environments were populated by a diversity of large animals that did not survive either the last dramatic climate change or the increasing power of humans. The volume of continental ice covering the land and its impact on the planet’s physiography∗ and vegetation have varied consistently. We can try to imagine extreme conditions: the very cold springtimes of the full glacials∗, and the warm springtimes of the rapid deglaciation phases, with enormous volumes of water feeding terrifying rivers. Most of this story is frozen in the ice cover of Greenland and Antarctica, the deep layers of which have been reached by human coring activities only over the past half century. Shorter cores have been drilled in high-altitude ice caps (e.g., in the Andes) that provide insight into other parts of the planet. The interpretation of the signals locked into the ice cores led to the reconstruction of climatic curves covering approximately the past 800 millennia. In addition, long sediment cores have been recovered from thousands of lakes across the globe and yielded data useful to estimate climatic trends based on pollen* records. In the past one to three million years, the continents and oceans were in roughly their present-day locations. Environmental factors, including tectonics (mountain uplift or closure of ocean gateways), interacted with the overall long-term oscillation in atmospheric carbon-dioxide concentration, which, in turn, influenced vegetation cover and ecosystem composition. Well-established glacial-interglacial∗ cycles impacted biotic dispersal∗ events at mid-to-high latitudes and determined the geographical restriction and expansion of tropical and subtropical (warm-temperate) biomes around the globe. This book chapter constitutes an imaginary field trip, presenting the reader with exemplary records of environments, plants, large mammals, and hominins impacted by cooling and warming phases, glaciations, changes in rainfall patterns, and sea level culminating in the world of today