A Data Mining Approach to Discover Genetic and Environmental Factors involved in Multifactoral Diseases

In this paper, we are interested in discovering genetic factors that are involved in multifactorial diseases. Therefore, experiments have been achieved by the Biological Institute of Lille and a lot of data has been generated. To exploit this data, data mining tools are required and we propose a 2-phase optimization approach using a specific genetic algorithm. During the first step, we select significant features with a specific genetic algorithm. Then, during the second step, we cluster affected individuals according to the features selected by the first phase. The paper describes the specificities of the genetic problem that we are studying and presents in details the genetic algorithm that we have developed to deal with this very large size problem of feature selection. Results on both artificial and real data are presented

Differential retention of transposable element-derived sequences in outcrossing Arabidopsis genomes

International audienceBackground: Transposable elements (TEs) are genomic parasites with major impacts on host genome architecture and host adaptation. A proper evaluation of their evolutionary significance has been hampered by the paucity of short scale phylogenetic comparisons between closely related species. Here, we characterized the dynamics of TE accumulation at the micro-evolutionary scale by comparing two closely related plant species, Arabidopsis lyrata and A. halleri. Results: Joint genome annotation in these two outcrossing species confirmed that both contain two distinct populations of TEs with either 'recent' or 'old' insertion histories. Identification of rare segregating insertions suggests that diverse TE families contribute to the ongoing dynamics of TE accumulation in the two species. Orthologous TE fragments (i.e. those that have been maintained in both species), tend to be located closer to genes than those that are retained in one species only. Compared to non-orthologous TE insertions, those that are orthologous tend to produce fewer short interfering RNAs, are less heavily methylated when found within or adjacent to genes and these tend to have lower expression levels. These findings suggest that long-term retention of TE insertions reflects their frequent acquisition of adaptive roles and/or the deleterious effects of removing nearly neutral TE insertions when they are close to genes. Conclusion: Our results indicate a rapid evolutionary dynamics of the TE landscape in these two outcrossing species, with an important input of a diverse set of new insertions with variable propensity to resist deletion

Molecular Diagnosis of Neonatal Diabetes Mellitus Using Next-Generation Sequencing of the Whole Exome

Background: Accurate molecular diagnosis of monogenic non-autoimmune neonatal diabetes mellitus (NDM) is critical for patient care, as patients carrying a mutation in KCNJ11 or ABCC8 can be treated by oral sulfonylurea drugs instead of insulin therapy. This diagnosis is currently based on Sanger sequencing of at least 42 PCR fragments from the KCNJ11, ABCC8, and INS genes. Here, we assessed the feasibility of using the next-generation whole exome sequencing (WES) for the NDM molecular diagnosis. Methodology/Principal Findings: We carried out WES for a patient presenting with permanent NDM, for whom mutations in KCNJ11, ABCC8 and INS and abnormalities in chromosome 6q24 had been previously excluded. A solution hybridization selection was performed to generate WES in 76 bp paired-end reads, by using two channels of the sequencing instrument. WES quality was assessed using a high-resolution oligonucleotide whole-genome genotyping array. From our WES with high-quality reads, we identified a novel non-synonymous mutation in ABCC8 (c.1455G.C/p.Q485H), despite a previous negative sequencing of this gene. This mutation, confirmed by Sanger sequencing, was not present in 348 controls and in the patient’s mother, father and young brother, all of whom are normoglycemic. Conclusions/Significance: WES identified a novel de novo ABCC8 mutation in a NDM patient. Compared to the current Sanger protocol, WES is a comprehensive, cost-efficient and rapid method to identify mutations in NDM patients. W

Instance nationale et multi-communauté de DIRAC pour France Grilles

DIRAC [DIRAC] [TSA-08] is a software framework for building distributed computing systems. It was primarily designed forthe needs of the LHCb [LHCb] Collaboration, and is now used by many other communities within EGI [EGI] as a primary wayof accessing grid resources. In France, dedicated instances of the service have been deployed in different locations toanswer specific needs. Building upon this existing expertise, France Grilles [FG] initiated last year a project to deploy anational, multi-community instance in order to share expertise and provide a consistent high-quality service. After describingDIRAC main aims and functionalities, this paper presents the motivations for such a project, as well as the wholeorganizational and technical process that led to the establishment of a production instance that already serves 13communities: astro.vo.eu-egee.org, biomed, esr, euasia, gilda, glast.org, prod.vo.eu-eela.eu, superbvo.org,vo.formation.idgrilles.fr, vo.france-asia.org, vo.france-grilles.fr, vo.msfg.fr and vo.mcia.fr

Contrasted Patterns of Molecular Evolution in Dominant and Recessive Self-Incompatibility Haplotypes in Arabidopsis

Self-incompatibility has been considered by geneticists a model system for reproductive biology and balancing selection, but our understanding of the genetic basis and evolution of this molecular lock-and-key system has remained limited by the extreme level of sequence divergence among haplotypes, resulting in a lack of appropriate genomic sequences. In this study, we report and analyze the full sequence of eleven distinct haplotypes of the self-incompatibility locus (S-locus) in two closely related Arabidopsis species, obtained from individual BAC libraries. We use this extensive dataset to highlight sharply contrasted patterns of molecular evolution of each of the two genes controlling self-incompatibility themselves, as well as of the genomic region surrounding them. We find strong collinearity of the flanking regions among haplotypes on each side of the S-locus together with high levels of sequence similarity. In contrast, the S-locus region itself shows spectacularly deep gene genealogies, high variability in size and gene organization, as well as complete absence of sequence similarity in intergenic sequences and striking accumulation of transposable elements. Of particular interest, we demonstrate that dominant and recessive S-haplotypes experience sharply contrasted patterns of molecular evolution. Indeed, dominant haplotypes exhibit larger size and a much higher density of transposable elements, being matched only by that in the centromere. Overall, these properties highlight that the S-locus presents many striking similarities with other regions involved in the determination of mating-types, such as sex chromosomes in animals or in plants, or the mating-type locus in fungi and green algae

Rural women’s participation in producer organizations: An analysis of the barriers that women face and strategies to foster equitable and effective participation

Over the last several decades, participation in producer organizations has become a key principle of development, enabling people’s empowerment, inclusiveness, and facilitating democracy. Producer organizations have become crucial actors to provide services to the rural poor, and women’s participation and leadership in producer organizations has become a focus of rural and agricultural development efforts. This review paper aims to document the factors that hinder women’s participation in producer organizations. The review identifies several factors as major barriers for women’s participation, including: socio-cultural norms; women’s double burden and triple roles; women’s status, age and previous membership in organizations; access to assets and resources; educational level; organizations’ rules of entry, and; legal and policy environment. The paper also provides a review of lessons and good practice that can be applied by Agricultural Research for Development institutions. The review identified strategies for strengthening women’s participation in producer organizations at the individual/household, community/producer organization, and policy level. The review found that at the individual/household level, strategies to improve individual capabilities and intra-household relations were crucial for promoting women’s participation and leadership in producer organizations. Similarly, at the producer organizational level strategies to ensure that the structures and governance mechanisms are more gender sensitive, and promote women’s inclusion, are crucial. Equally important are policies for promoting gender-sensitive producer organizations and specific measures geared at promoting women’s active participation in producers’ organizations

The Interaction between Selection, Demography and Selfing and How It Affects Population Viability

International audiencePopulation extinction due to the accumulation of deleterious mutations has only been considered to occur at small population sizes, large sexual populations being expected to efficiently purge these mutations. However, little is known about how the mutation load generated by segregating mutations affects population size and, eventually, population extinction. We propose a simple analytical model that takes into account both the demographic and genetic evolution of populations, linking population size, density dependence, the mutation load, and self-fertilisation. Analytical predictions were found to be relatively good predictors of population size and probability of population viability when verified using an explicit individual based stochastic model. We show that initially large populations do not always reach mutation-selection balance and can go extinct due to the accumulation of segregating deleterious mutations. Population survival depends not only on the relative fitness and demographic stochasticity, but also on the interaction between the two. When deleterious mutations are recessive, self-fertilisation affects viability non-monotonically and genomic cold-spots could favour the viability of outcrossing populations

Genomewide Search for Type 2 Diabetes–Susceptibility Genes in French Whites: Evidence for a Novel Susceptibility Locus for Early-Onset Diabetes on Chromosome 3q27-qter and Independent Replication of a Type 2–Diabetes Locus on Chromosome 1q21–q24

Despite recent advances in the molecular genetics of type 2 diabetes, the majority of susceptibility genes in humans remain to be identified. We therefore conducted a 10-cM genomewide search (401 microsatellite markers) for type 2 diabetes–related traits in 637 members of 143 French pedigrees ascertained through multiple diabetic siblings, to map such genes in the white population. Nonparametric two-point and multipoint linkage analyzes—using the MAPMAKER-SIBS (MLS) and MAXIMUM-BINOMIAL-LIKELIHOOD (MLB) programs for autosomal markers and the ASPEX program for chromosome X markers—were performed with six diabetic phenotypes: diabetes and diabetes or glucose intolerance (GI), as well as with each of the two phenotypes associated with normal body weight (body-mass index<27 kg/m(2)) or early age at diagnosis (<45 years). In a second step, high-resolution genetic mapping (∼2 cM) was performed in regions on chromosomes 1 and 3 loci showing the strongest linkage to diabetic traits. We found evidence for linkage with diabetes or GI diagnosed at age <45 years in 92 affected sib pairs from 55 families at the D3S1580 locus on chromosome 3q27-qter using MAPMAKER-SIBS (MLS = 4.67, P=.000004), supported by the MLB statistic (MLB-LOD=3.43, P=.00003). We also found suggestive linkage between the lean diabetic status and markers APOA2–D1S484 (MLS = 3.04, P=.00018; MLB-LOD=2.99, P=.00010) on chromosome 1q21-q24. Several other chromosomal regions showed indication of linkage with diabetic traits, including markers on chromosome 2p21-p16, 10q26, 20p, and 20q. These results (a) showed evidence for a novel susceptibility locus for type 2 diabetes in French whites on chromosome 3q27-qter and (b) confirmed the previously reported diabetes-susceptibility locus on chromosome 1q21-q24. Saturation on both chromosomes narrowed the regions of interest down to an interval of <7 cM