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International audience; ObjectivesTo improve our understanding of the global epidemiology of common respiratory viruses by analysing their contemporaneous incidence at multiple sites.Methods2010–2015 incidence data for influenza A (IAV), influenza B (IBV), respiratory syncytial (RSV) and parainfluenza (PIV) virus infections were collected from 18 sites (14 countries), consisting of local (n = 6), regional (n = 9) and national (n = 3) laboratories using molecular diagnostic methods. Each site submitted monthly virus incidence data, together with details of their patient populations tested and diagnostic assays used.ResultsFor the Northern Hemisphere temperate countries, the IAV, IBV and RSV incidence peaks were 2–6 months out of phase with those in the Southern Hemisphere, with IAV having a sharp out-of-phase difference at 6 months, whereas IBV and RSV showed more variable out-of-phase differences of 2–6 months. The tropical sites Singapore and Kuala Lumpur showed fluctuating incidence of these viruses throughout the year, whereas subtropical sites such as Hong Kong, Brisbane and Sydney showed distinctive biannual peaks for IAV but not for RSV and PIV.ConclusionsThere was a notable pattern of synchrony of IAV, IBV and RSV incidence peaks globally, and within countries with multiple sampling sites (Canada, UK, Australia), despite significant distances between these sites.

International audience; Sesame allergy is a public health problem in many countries around the world. The purpose of this study is to determine the occurrence of sesame allergen in unlabelled or labelled free-sesame Middle Eastern foods with or without Precautionary Allergen Labelling (PAL) 'may contain' and estimate the risk incurred by the Canadian population allergic to sesame with a focus on products purchased in Middle Eastern grocery stores and bakeries in Montreal, Canada. A total of 571 samples were analysed to determine the level of sesame protein. Of the 571 samples analysed, 19% (109/571) contained sesame (results >LOQ) with concentrations of sesame proteins varying between 0.5 and 1,875 mg kg-1 and 35% (199/571) contained traces (a value between LOD and LOQ). Unpackaged products were found to present the highest proportion of sesame containing samples (36%). For packaged products, 16% (27/173) of samples with PAL and 3% (5/173) without PAL were found to contain sesame. A probabilistic approach was used to estimate the risk incurred by the Canadian consumers allergic to sesame. Our evaluation estimated that 33 to 308 allergic reactions may occur out of 10 000 individuals ingesting one type of bakery product contaminated at a level of 0.6-74 mg kg-1 sesame proteins. The incidence and level of sesame cross-contact reported in this study demonstrate that sesame allergic consumers could react if they ignore the precautionary allergen statements on product labels. Attention to sesame as a potential cross-contact agent and as a priority allergen calls for better management, given the growing interest in this ingredient to be included in food formulations. Enhanced risk management efforts must be coupled with targeted risk communication covering both producers and consumers as to the need to adopt and an approach for the application of precautionary allergen labelling based on risk.

International audience; Polyploidization is a dominant feature of flowering plant evolution. However, detailed genomic analyses of the interpopulation diversification of polyploids following genome duplication are still in their infancy, mainly because of methodological limits, both in terms of sequencing and computational analyses. The shepherd's purse (Capsella bursa-pastoris) is one of the most common weed species in the world. It is highly self-fertilizing, and recent genomic data indicate that it is an allopolyploid, resulting from hybridization between the ancestors of the diploid species Capsella grandiflora and Capsella orientalis. Here, we investigated the genomic diversity of C. bursa-pastoris, its population structure and demographic history, following allopolyploidization in Eurasia. To that end, we genotyped 261 C. bursa-pastoris accessions spread across Europe, the Middle East and Asia, using genotyping-by-sequencing, leading to a total of 4274 SNPs after quality control. Bayesian clustering analyses revealed three distinct genetic clusters in Eurasia: one cluster grouping samples from Western Europe and Southeastern Siberia, the second one centred on Eastern Asia and the third one in the Middle East. Approximate Bayesian computation (ABC) supported the hypothesis that C. bursa-pastoris underwent a typical colonization history involving low gene flow among colonizing populations, likely starting from the Middle East towards Europe and followed by successive human-mediated expansions into Eastern Asia. Altogether, these findings bring new insights into the recent multistage colonization history of the allotetraploid C. bursa-pastoris and highlight ABC and genotyping-by-sequencing data as promising but still challenging tools to infer demographic histories of selfing allopolyploids.

International audience; Significance We compared the information provided by whole-exome sequencing (WES) and genome-wide single-nucleotide variant arrays in terms of principal component analysis, homozygosity rate estimation, and linkage analysis using 110 subjects originating from different regions of the world. WES provided an accurate prediction of population substructure using high-quality variants with a minor allele frequency > 2% and reliable estimation of homozygosity rates using runs of homozygosity. Finally, homozygosity mapping in 15 consanguineous families showed that WES led to powerful linkage analyses, particularly in coding regions. Overall, our study shows that WES could be used for several analyses that are very helpful to optimize the search for disease-causing exome variants. AbstractPrincipal component analysis (PCA), homozygosity rate estimations, and linkage studies in humans are classically conducted through genome-wide single-nucleotide variant arrays (GWSA). We compared whole-exome sequencing (WES) and GWSA for this purpose. We analyzed 110 subjects originating from different regions of the world, including North Africa and the Middle East, which are poorly covered by public databases and have high consanguinity rates. We tested and applied a number of quality control (QC) filters. Compared with GWSA, we found that WES provided an accurate prediction of population substructure using variants with a minor allele frequency > 2% (correlation = 0.89 with the PCA coordinates obtained by GWSA). WES also yielded highly reliable estimates of homozygosity rates using runs of homozygosity with a 1,000-kb window (correlation = 0.94 with the estimates provided by GWSA). Finally, homozygosity mapping analyses in 15 families including a single offspring with high homozygosity rates showed that WES provided 51% less genome-wide linkage information than GWSA overall but 97% more information for the coding regions. At the genome-wide scale, 76.3% of linked regions were found by both GWSA and WES, 17.7% were found by GWSA only, and 6.0% were found by WES only. For coding regions, the corresponding percentages were 83.5%, 7.4%, and 9.1%, respectively. With appropriate QC filters, WES can be used for PCA and adjustment for population substructure, estimating homozygosity rates in individuals, and powerful linkage analyses, particularly in coding regions.

International audience; Multilocus microsatellite typing (MLMT) was employed to compare strains of Leishmania donovani belonging to the MON-37 zymodeme (MON-37 strains) from Cyprus and Israel to MON-37 strains from the Indian subcontinent, the Middle East, China and East Africa as well as strains of other zymodemes. The MLMT data were processed with a distance-based method for construction of phylogenetic trees, factorial correspondence analysis and a Bayesian model-based clustering algorithm. All three approaches assigned the MON-37 strains to different distantly related genetically defined subgroups, corresponding to their geographical origin. Specifically, the Kenyan, Sri Lankan and Indian MON-37 strains were genetically closer to strains of other zymodemes from the same regions than to MON-37 strains from other areas. MON-37 strains from Cyprus and Israel were clearly different not only among themselves, but also compared to all the other MON-37 strains studied and could, therefore, be autochthonous. This study showed that the zymodeme MON-37 is paraphyletic and does not reflect the genetic relationship between strains of different geographical origin.

International audience; Several haemorrhagic fevers are caused by highly pathogenic viruses that must be handled in Biosafety level 4 (BSL-4) containment. These zoonotic infections have an important impact on public health and the development of a rapid and differential diagnosis in case of outbreak in risk areas represents a critical priority. We have demonstrated the potential of a DNA resequencing microarray (PathogenID v2.0) for this purpose. The microarray was first validated in vitro using supernatants of cells infected with prototype strains from five different families of BSL-4 viruses (e.g. families Arenaviridae, Bunyaviridae, Filoviridae, Flaviviridae and Paramyxoviridae). RNA was amplified based on isothermal amplification by Phi29 polymerase before hybridization. We were able to detect and characterize Nipah virus and Crimean-Congo haemorrhagic fever virus (CCHFV) in the brains of experimentally infected animals. CCHFV was finally used as a paradigm for epidemics because of recent outbreaks in Turkey, Kosovo and Iran. Viral variants present in human sera were characterized by BLASTN analysis. Sensitivity was estimated to be 10(5) -10(6) PFU/mL of hybridized cDNA. Detection specificity was limited to viral sequences having ~13-14% of global divergence with the tiled sequence, or stretches of ~20 identical nucleotides. These results highlight the benefits of using the PathogenID v2.0 resequencing microarray to characterize geographical variants in the follow-up of haemorrhagic fever epidemics; to manage patients and protect communities; and in cases of bioterrorism.

Background Tunisia is a North African country of 10 million inhabitants. The native background population is Berber. However, throughout its history, Tunisia has been the site of invasions and migratory waves of allogenic populations and ethnic groups such as Phoenicians, Romans, Vandals, Arabs, Ottomans and French. Like neighbouring and Middle Eastern countries, the Tunisian population shows a relatively high rate of consanguinity and endogamy that favor expression of recessive genetic disorders at relatively high rates. Many factors could contribute to the recurrence of monogenic morbid trait expression. Among them, founder mutations that arise in one ancestral individual and diffuse through generations in isolated communities. Method We report here on founder mutations in the Tunisian population by a systematic review of all available data from PubMed, other sources of the scientific literature as well as unpublished data from our research laboratory. Results We identified two different classes of founder mutations. The first includes founder mutations so far reported only among Tunisians that are responsible for 30 genetic diseases. The second group represents founder haplotypes described in 51 inherited conditions that occur among Tunisians and are also shared with other North African and Middle Eastern countries. Several heavily disabilitating diseases are caused by recessive founder mutations. They include, among others, neuromuscular diseases such as congenital muscular dystrophy and spastic paraglegia and also severe genodermatoses such as dystrophic epidermolysis bullosa and xeroderma pigmentosa. Conclusion This report provides informations on founder mutations for 73 genetic diseases either specific to Tunisians or shared by other populations. Taking into account the relatively high number and frequency of genetic diseases in the region and the limited resources, screening for these founder mutations should provide a rapid and cost effective tool for molecular diagnosis. Indeed, our report should help designing appropriate measures for carrier screening, better evaluation of diseases burden and setting up of preventive measures at the regional level.

Background For the first time in France in a population-based survey, this study sought to investigate the potential impact of migration origin and the proportion of lifetime spent in mainland France on body mass index (BMI) and overweight in adults living in the Paris metropolitan area. Methods A representative, population-based, random sample of the adult, French speaking population of the Paris metropolitan area was interviewed in 2005. Self-reported BMI (BMI = weight/height2) and overweight (BMI ≥ 25) were our 2 outcomes of interest. Two variables were constructed to estimate individuals’ migration origin: parental nationality and the proportion of lifetime spent in mainland France, as declared by the participants. We performed multilevel regression models among different gender and age groups, adjusted for demographics and socioeconomic status. Results In women, a parental origin in the Middle East or North Africa (MENA) was associated with a higher risk of being overweight (especially before the age of 55) and a higher BMI (between 35 and 54 years of age), and so were women of Sub-Sahara African parental origin in the middle age category. Only in the youngest men (< 35 years of age) did we observe any association with parental nationality, with a higher BMI when having a MENA parentage. Regarding the association between the proportion of lifetime spent in France and overweight, we observed that, in women, a proportion of 50% to 99% appeared to be associated with overweight, especially after the age of 35. In men, having spent more than half of one’s lifetime in France was associated with a higher risk of overweight among oldest men. Conclusions Our results plea for potential cultural determinants of overweight in the migrant and migrants-born populations in the French context of the capital region. Taking into account the people’ family and personal migration histories may be an important issue in public health research and policies on overweight and obesity prevention.

This work was supported by the German Research Foundation (DFG Ta434/2-1 and SFB-TRR57) and the Iranian Ministry of Health (KH/16716 to S.A.).; International audience; Hepatitis B virus (HBV) viral load and its genotype play important roles in clinical outcome, management of disease and response to antiviral therapy. In many parts of the world such as Europe or the Middle East, distinguishing HBV genotype D from non-D is most relevant for treatment decisions, because genotype D-infected patients respond poorly to interferon-based therapeutic regimens. Here, we developed an in-house real-time PCR to concordantly assess HBV genotype (D vs non-D) based on melt curve analysis and quantify the viral load. Genotype distinction was established with control plasmids of all HBV genotypes and validated with 57 clinical samples from patients infected with six different HBV genotypes. Our in-house real-time PCR assay could discriminate HBV genotype D from non-D using single-step melt curve analysis with a 2 °C difference in the melt curve temperature in all samples tested. Viral load quantification was calibrated with the WHO HBV international standard, demonstrating an excellent correlation with a commercial kit (r = 0.852; P < 0.0001) in a linear range from 3.2 × 10(2) to 3.2 × 10(10) IU/mL. In conclusion, we developed a rapid, simple and cost-effective method to simultaneously quantify and distinguish HBV genotypes D from non-D with a single-step PCR run and melt curve analysis. This assay should be a useful diagnostic alternative to aid clinical decisions about initiation and choice of antiviral therapy, especially in geographical regions with a high prevalence of HBV genotype D.

International audience; The combination of recessively inherited cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) was first reported by Jalili and Smith in 1988 in a family subsequently linked to a locus on chromosome 2q11, and it has since been reported in a second small family. We have identified five further ethnically diverse families cosegregating CRD and AI. Phenotypic characterization of teeth and visual function in the published and new families reveals a consistent syndrome in all seven families, and all link or are consistent with linkage to 2q11, confirming the existence of a genetically homogenous condition that we now propose to call Jalili syndrome. Using a positional-candidate approach, we have identified mutations in the CNNM4 gene, encoding a putative metal transporter, accounting for the condition in all seven families. Nine mutations are described in all, three missense, three terminations, two large deletions, and a single base insertion. We confirmed expression of Cnnm4 in the neural retina and in ameloblasts in the developing tooth, suggesting a hitherto unknown connection between tooth biomineralization and retinal function. The identification of CNNM4 as the causative gene for Jalili syndrome, characterized by syndromic CRD with AI, has the potential to provide new insights into the roles of metal transport in visual function and biomineralization.

International audience; Until the early 1990s, pentavalent antimony was the only documented first-line drug employed for the treatment of zoonotic visceral leishmaniasis (VL) in the Mediterranean, with reported cure rates exceeding 95% in immunocompetent patients. The emergence of antimony resistance in other endemic settings and the increase in drug options have stimulated re-evaluation of the current therapeutic approaches and outcomes in Mediterranean countries. A scientific consortium ('LeishMed' network) collected updated information from collaborating clinical health centres of 11 endemic countries of Southern Europe, Northern Africa and the Middle East. In contrast with the previous situation, VL is now treated differently in the region, basically through three approaches: (1) In Northern Africa and in part of the Middle East, pentavalent antimony is still the mainstay for therapy, with no alternative drug options for treating relapses; (2) In some European countries and Israel, both pentavalent antimony and lipid-associated amphotericin B (AmB) formulations are used as first-line drugs, although in different patients' categories; (3) In other countries of Europe, mainly liposomal AmB is employed. Importantly, cure rates exhibited by different drugs, including antimonials in areas where they are still in routine use, are similarly high (>/=95%) in immunocompetent patients. Our findings show that antimony resistance is not an emerging problem in the Mediterranean. A country's wealth affects the treatment choice, which represents a balance between drug efficacy, toxicity and cost, and costs associated with patient's care.

Ongoing modernization in India has elevated the prevalence of many complex genetic diseases associated with a western lifestyle and diet to near-epidemic proportions. However, although India comprises more than one sixth of the world's human population, it has largely been omitted from genomic surveys that provide the backdrop for association studies of genetic disease. Here, by genotyping India-born individuals sampled in the United States, we carry out an extensive study of Indian genetic variation. We analyze 1,200 genome-wide polymorphisms in 432 individuals from 15 Indian populations. We find that populations from India, and populations from South Asia more generally, constitute one of the major human subgroups with increased similarity of genetic ancestry. However, only a relatively small amount of genetic differentiation exists among the Indian populations. Although caution is warranted due to the fact that United States–sampled Indian populations do not represent a random sample from India, these results suggest that the frequencies of many genetic variants are distinctive in India compared to other parts of the world and that the effects of population heterogeneity on the production of false positives in association studies may be smaller in Indians (and particularly in Indian-Americans) than might be expected for such a geographically and linguistically diverse subset of the human population., Synopsis Genomic studies of human genetic variation are useful for investigating human evolutionary history, as well as for designing strategies for identifying disease-related genes. Despite its large population and its increasing complex genetic disease burden as a result of modernization, India has been excluded from most of the largest genomic surveys. The authors performed an extensive investigation of Indian genetic diversity and population relationships, sampling 15 groups of India-born immigrants to the United States and genotyping each individual at 1,200 genetic markers genome-wide. Populations from India, and groups from South Asia more generally, form a genetic cluster, so that individuals placed within this cluster are more genetically similar to each other than to individuals outside the cluster. However, the amount of genetic differentiation among Indian populations is relatively small. The authors conclude that genetic variation in India is distinctive with respect to the rest of the world, but that the level of genetic divergence is smaller in Indians than might be expected for such a geographically and linguistically diverse group.