Robust physical methods that enrich genomic regions identical by descent for linkage studies: confirmation of a locus for osteogenesis imperfecta

<p>Abstract</p> <p>Background</p> <p>The monogenic disease osteogenesis imperfecta (OI) is due to single mutations in either of the collagen genes ColA1 or ColA2, but within the same family a given mutation is accompanied by a wide range of disease severity. Although this phenotypic variability implies the existence of modifier gene variants, genome wide scanning of DNA from OI patients has not been reported. Promising genome wide marker-independent physical methods for identifying disease-related loci have lacked robustness for widespread applicability. Therefore we sought to improve these methods and demonstrate their performance to identify known and novel loci relevant to OI.</p> <p>Results</p> <p>We have improved methods for enriching regions of identity-by-descent (IBD) shared between related, afflicted individuals. The extent of enrichment exceeds 10- to 50-fold for some loci. The efficiency of the new process is shown by confirmation of the identification of the Col1A2 locus in osteogenesis imperfecta patients from Amish families. Moreover the analysis revealed additional candidate linkage loci that may harbour modifier genes for OI; a locus on chromosome 1q includes COX-2, a gene implicated in osteogenesis.</p> <p>Conclusion</p> <p>Technology for physical enrichment of IBD loci is now robust and applicable for finding genes for monogenic diseases and genes for complex diseases. The data support the further investigation of genetic loci other than collagen gene loci to identify genes affecting the clinical expression of osteogenesis imperfecta. The discrimination of IBD mapping will be enhanced when the IBD enrichment procedure is coupled with deep resequencing.</p

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Commande optimale minimax d'un systeme non stationnaire : etude theorique de l'influence de la forme de debit d'insufflation sur les regimes des pressions aeriennes en ventilation mecanique

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Mesures compensatoires des atteintes à l’environnement dans les projets d’infrastructures : de nouvelles exigences réglementaires pour une amélioration des pratiques ?

La compensation des impacts résiduels des aménagements sur les milieux naturels prévue par la loi depuis 1976 n’est pas toujours bien appliquée. La réglementation s'est renforcée et avec elle, s'imposent désormais de nouvelles exigences techniques qui complexifient les dossiers et accentuent la pression foncière. Mais il reste à combler des lacunes importantes pour améliorer la prise en compte de la biodiversité et des services écosystémiques

Prise en compte de la biodiversité dans les projets d’aménagement : comment améliorer la commande des études environnementales ?

Better biodiversity integration (in particular daily life nature and ecosystems functioning) strengthen impact studies requirement, compensatory measures and ecological network (Trame verte et bleue) integration into both fitting out projects and town planning documents. This requires numerous and relevant environmental datas in order to evaluate project possible impacts. Based on cities biodiversity studies and transportation facilities impact, we point out gaps or problems in inventory needs or natural datas recollection formulation. We provide ideas for better relations and better mutual expectations between planners and natural data providers

Varia

Le Bulletin de l’Institut français d’archéologie orientale (BIFAO) couvre l’ensemble des champs de l’égyptologie depuis sa première publication en 1901. Le BIFAO 119 regroupe 13 contributions dont l’aire chronologique s’étend de l’Ancien Empire jusqu’à l’époque byzantine et qui illustrent l’état des recherches actuelles dans les domaines de l’archéologie, l’épigraphie, la lexicographie, l’iconographie, la religion et la philologie. The Bulletin de l’Institut français d’archéologie orientale (BIFAO) has covered the entire field of egyptology since its first appearance in 1901. The BIFAO 119 holds 13 contributions with a chronological spread from the Old Kingdom up to the Byzantine period, and it illustrates the present state of research in the areas of archaeology, epigraphy, lexicography, iconography, religion and philology