Innovations in Primate Interneuron Repertoire, bioRxiv, 2019-07-24

ABSTRACTPrimates and rodents, which descended from a common ancestor more than 90 million years ago, exhibit profound differences in behavior and cognitive capacity. Modifications, specializations, and innovations to brain cell types may have occurred along each lineage. We used Drop-seq to profile RNA expression in more than 184,000 individual telencephalic interneurons from humans, macaques, marmosets, and mice. Conserved interneuron types varied significantly in abundance and RNA expression between mice and primates, but varied much more modestly among primates. In adult primates, the expression patterns of dozens of genes exhibited spatial expression gradients among neocortical interneurons, suggesting that adult neocortical interneurons are imprinted by their local cortical context. In addition, we found that an interneuron type previously associated with the mouse hippocampus—the “ivy cell”, which has neurogliaform characteristics—has become abundant across the neocortex of humans, macaques, and marmosets. The most striking innovation was subcortical we identified an abundant striatal interneuron type in primates that had no molecularly homologous cell population in mouse striatum, cortex, thalamus, or hippocampus. These interneurons, which expressed a unique combination of transcription factors, receptors, and neuropeptides, including the neuropeptide TAC3, constituted almost 30% of striatal interneurons in marmosets and humans. Understanding how gene and cell-type attributes changed or persisted over the evolutionary divergence of primates and rodents will guide the choice of models for human brain disorders and mutations and help to identify the cellular substrates of expanded cognition in humans and other primates.

biorxiv neuroscience 100-200-users 2019

The Genetic History of France, bioRxiv, 2019-07-24

ABSTRACTThe study of the genetic structure of different countries within Europe has provided significant insights into their demographic history and their actual stratification. Although France occupies a particular location at the end of the European peninsula and at the crossroads of migration routes, few population genetic studies have been conducted so far with genome-wide data. In this study, we analyzed SNP-chip genetic data from 2 184 individuals born in France who were enrolled in two independent population cohorts. Using FineStructure, six different genetic clusters of individuals were found that were very consistent between the two cohorts. These clusters match extremely well the geography and overlap with historical and linguistic divisions of France. By modeling the relationship between genetics and geography using EEMS software, we were able to detect gene flow barriers that are similar in the two cohorts and corresponds to major French rivers or mountains. Estimations of effective population sizes using IBDNe program also revealed very similar patterns in both cohorts with a rapid increase of effective population sizes over the last 150 generations similar to what was observed in other European countries. A marked bottleneck is also consistently seen in the two datasets starting in the fourteenth century when the Black Death raged in Europe. In conclusion, by performing the first exhaustive study of the genetic structure of France, we fill a gap in the genetic studies in Europe that would be useful to medical geneticists but also historians and archeologists.

biorxiv genetics 100-200-users 2019

Tree Lab Portable genomics for early detection of plant viruses and pests in Sub-Saharan Africa, bioRxiv, 2019-07-20

AbstractIn this case study we successfully teamed the PDQeX DNA purification technology developed by MicroGEM, New Zealand, with the MinION and MinIT mobile sequencing devices developed by Oxford Nanopore Technologies to produce an effective point-of-need field diagnostic system. The PDQeX extracts DNA using a cocktail of thermophilic proteinases and cell wall degrading enzymes, thermo-responsive extractor cartridges and a temperature control unit. This single-step closed system delivers purified DNA with no cross contamination. The MinIT is a newly released data processing unit that converts MinION raw signal output into base called data locally in real time, removing the need for high specification computers and large file transfers from the field. All three devices are battery powered with an exceptionally small footprint that facilitates transport and set up.To evaluate and validate capability of the system for unbiased pathogen identification by realtime sequencing in a farmer’s field setting, we analysed samples collected from cassava plants grown by subsistence farmers in three sub-Sahara African countries (Tanzania, Uganda and Kenya). A range of viral pathogens, all with similar symptoms, greatly reduce yield or completely destroy cassava crops. 800 million people worldwide depend on cassava for food and yearly income, and viral diseases are a significant constraint on its production (<jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpscassavavirusactionproject.com>httpscassavavirusactionproject.com<jatsext-link>). Early pathogen detection at a molecular level has great potential to rescue crops within a single growing season by providing results that inform decisions on disease management, use of appropriate virus resistant or replacement planting.This case study presented conditions of working in-field with limited or no access to mains power, laboratory infrastructure, internet connectivity and highly variable ambient temperature. An additional challenge is that, generally, plant material contains inhibitors of downstream molecular processes making effective DNA purification critical. We successfully undertook real-time on-farm genome sequencing of samples collected from cassava plants on three farms, one in each country. Cassava mosaic begomoviruses were detected by sequencing leaf, stem, tuber and insect samples. The entire process, from arrival on farm to diagnosis including sample collection, processing and provisional sequencing results was complete in under 4 hours. The need for accurate, rapid and on-site diagnosis grows as globalized human activity accelerates. This technical breakthrough has applications that are relevant to human and animal health, environmental management and conservation.

biorxiv genomics 100-200-users 2019

Comparison of adopted and non-adopted individuals reveals gene-environment interplay for education in the UK Biobank, bioRxiv, 2019-07-19

AbstractIndividual-level polygenic scores can now explain ∼10% of the variation in number of years of completed education. However, associations between polygenic scores and education capture not only genetic propensity but information about the environment that individuals are exposed to. This is because individuals passively inherit effects of parental genotypes, since their parents typically also provide the rearing environment. In other words, the strong correlation between offspring and parent genotypes results in an association between the offspring genotypes and the rearing environment. This is termed passive gene-environment correlation. We present an approach to test for the extent of passive gene-environment correlation for education without requiring intergenerational data. Specifically, we use information from 6311 individuals in the UK Biobank who were adopted in childhood to compare genetic influence on education between adoptees and non-adopted individuals. Adoptees’ rearing environments are less correlated with their genotypes, because they do not share genes with their adoptive parents. We find that polygenic scores are twice as predictive of years of education in non-adopted individuals compared to adoptees (R2= 0.074 vs 0.037, difference test p= 8.23 × 10−24). We provide another kind of evidence for the influence of parental behaviour on offspring education individuals in the lowest decile of education polygenic score attain significantly more education if they are adopted, possibly due to educationally supportive adoptive environments. Overall, these results suggest that genetic influences on education are mediated via the home environment. As such, polygenic prediction of educational attainment represents gene-environment correlations just as much as it represents direct genetic effects.

biorxiv genomics 100-200-users 2019

 

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