New and improved demonstrations, each illustrating a single scientific paper

Thesis (Ed.M.)--Boston Universit

Ultra-rare genetic variation in common epilepsies: a case-control sequencing study

BACKGROUND:Despite progress in understanding the genetics of rare epilepsies, the more common epilepsies have proven less amenable to traditional gene-discovery analyses. We aimed to assess the contribution of ultra-rare genetic variation to common epilepsies. METHODS:We did a case-control sequencing study with exome sequence data from unrelated individuals clinically evaluated for one of the two most common epilepsy syndromes: familial genetic generalised epilepsy, or familial or sporadic non-acquired focal epilepsy. Individuals of any age were recruited between Nov 26, 2007, and Aug 2, 2013, through the multicentre Epilepsy Phenome/Genome Project and Epi4K collaborations, and samples were sequenced at the Institute for Genomic Medicine (New York, USA) between Feb 6, 2013, and Aug 18, 2015. To identify epilepsy risk signals, we tested all protein-coding genes for an excess of ultra-rare genetic variation among the cases, compared with control samples with no known epilepsy or epilepsy comorbidity sequenced through unrelated studies. FINDINGS:We separately compared the sequence data from 640 individuals with familial genetic generalised epilepsy and 525 individuals with familial non-acquired focal epilepsy to the same group of 3877 controls, and found significantly higher rates of ultra-rare deleterious variation in genes established as causative for dominant epilepsy disorders (familial genetic generalised epilepsy: odd ratio [OR] 2·3, 95% CI 1·7-3·2, p=9·1 × 10-8; familial non-acquired focal epilepsy 3·6, 2·7-4·9, p=1·1 × 10-17). Comparison of an additional cohort of 662 individuals with sporadic non-acquired focal epilepsy to controls did not identify study-wide significant signals. For the individuals with familial non-acquired focal epilepsy, we found that five known epilepsy genes ranked as the top five genes enriched for ultra-rare deleterious variation. After accounting for the control carrier rate, we estimate that these five genes contribute to the risk of epilepsy in approximately 8% of individuals with familial non-acquired focal epilepsy. Our analyses showed that no individual gene was significantly associated with familial genetic generalised epilepsy; however, known epilepsy genes had lower p values relative to the rest of the protein-coding genes (p=5·8 × 10-8) that were lower than expected from a random sampling of genes. INTERPRETATION:We identified excess ultra-rare variation in known epilepsy genes, which establishes a clear connection between the genetics of common and rare, severe epilepsies, and shows that the variants responsible for epilepsy risk are exceptionally rare in the general population. Our results suggest that the emerging paradigm of targeting of treatments to the genetic cause in rare devastating epilepsies might also extend to a proportion of common epilepsies. These findings might allow clinicians to broadly explain the cause of these syndromes to patients, and lay the foundation for possible precision treatments in the future. FUNDING:National Institute of Neurological Disorders and Stroke (NINDS), and Epilepsy Research UK

Manipulation of Agricultural Habitats to Improve Conservation Biological Control in South America

International audienceStable and diversified agroecosystems provide farmers with important ecosystem services, which are unfortunately being lost at an alarming rate under the current conventional agriculture framework. Nevertheless, this concern can be tackled by using ecological intensification as an alternative strategy to recuperate ecosystem services (e.g., biological control of pests). To this end, the manipulation of agricultural habitats to enhance natural enemy conservation has been widely explored and reported in Western Europe and North America, whereas in other parts of the world, the investigation of such topic is lagging behind (e.g., South America). In this forum, we gathered published and unpublished information on the different ecological habitat management strategies that have been implemented in South America and their effects on pest control. Additionally, we identify the various challenges and analyze the outlook for the science of conservation biological control in South America. More specifically, we reviewed how different agricultural practices and habitat manipulation in South America have influenced pest management through natural enemy conservation. The main habitat manipulations reported include plant diversification (intercropping, insectary plants, agroforestry), conservation and management of non-crop vegetation, and application of artificial foods. Overall, we noticed that there is a significant discrepancy in the amount of research on conservation biological control among South American countries, and we found that, although intercropping, polycultures, and crop rotation have been reported in agroecosystems since pre-Inca times, more systematic studies are required to evaluate the true effects of habitat management to implement conservation biological control for pest control in South America