Use of maternal information for QTL detection in a (grand)daughter design

In a (grand)daughter design, maternal information is often neglected because the number of progeny per dam is limited. The number of dams per maternal grandsire (MGS), however, could be large enough to contribute to QTL detection. But dams and MGS usually are not genotyped, there are two recombination opportunities between the MGS and the progeny, and at a given location, only half the progeny receive a MGS chromosomal segment. A 3-step procedure was developed to estimate: (1) the marker phenotypes probabilities of the MGS; (2) the probability of each possible MGS haplotype; (3) the probabilities that the progeny receives either the first, or second MGS segment, or a maternal grandam segment. These probabilities were used for QTL detection in a linear model including the effects of sire, MGS, paternal QTL, MGS QTL and maternal grandam QTL. Including the grandam QTL effect makes it possible to detect QTL in the grandam population, even when MGS are not informative. The detection power, studied by simulation, was rather high, provided that MGS family size was greater than 50. Using maternal information in the French dairy cattle granddaughter design made it possible to detect 23 additional QTL genomewise significant

Augustin, du songe à la lumière. Sur La Vision de saint Augustin, de Carpaccio

La Vision de saint Augustin, célèbre tableau de Carpaccio, n’est pas seulement la description d’un cabinet d’érudit à la Renaissance. Savante construction d’un espace perspectif, cette peinture repose sur l’acte d’écrire comme support essentiel de la valeur symbolique accordée aux objets qui, multiples et précis, assurent le lien entre les mondes terrestre et céleste, dont la Vision est le cœur. L’Augustin de Carpaccio pourtant ne voit pas : il songe, comme la sainte Ursule d’une autre peinture de l’artiste, avec laquelle celle-ci entretient de singulières relations. Le songe permet à Augustin, par le truchement de la musique, d’approcher le Divin dont l’expression majeure est cette lumière surnaturelle imprégnant tout le tableau.The Vision of Saint Augustine, the famous painting by Carpaccio, is not merely the description of a learned man’s study during the Renaissance. Standing as a complex arrangement of space set in perspective, this painting is based upon the act of writing as the essential substance of the symbolic value granted to things; numerous and precise, they stand out as the links between terrestrial and celestial worlds, the vision of which is the heart. However, Carpaccio’s Augustine does not see: he dreams, like Saint Ursula on another of the artist’s paintings, which reminds us peculiar relationships. Thanks to music, dreaming almost enables Augustine to reach the Divine which is best expressed in the supernatural light permeating the whole picture

Fontaine (Haute-Saône), troisième fondation monastique de saint Colomban en Gaule : état des recherches et découvertes récentes

Introduction Le monastère de Fontaine fut fondé à la toute fin du vie siècle par le moine irlandais saint Colomban, peu après ceux d’Annegray et Luxeuil. On le situe conventionnellement au lieu-dit le Prieuré, au centre du village de Fontaine-lès-Luxeuil (Haute-Saône). À l’exception de quelques bâtiments du xviiie siècle, ses vestiges ont aujourd’hui disparu. Les moines de Fontaine vécurent sous la règle colombanienne, d’inspiration irlandaise, avant d’adopter au ixe siècle, comme tous les au..

A special case of reduced rank models for identification and modelling of time varying effects in survival analysis

Flexible survival models are in need when modelling data from long term follow-up studies. In many cases, the assumption of proportionality imposed by a Cox model will not be valid. Instead, a model that can identify time varying effects of fixed covariates can be used. Although there are several approaches that deal with this problem, it is not always straightforward how to choose which covariates should be modelled having time varying effects and which not. At the same time, it is up to the researcher to define appropriate time functions that describe the dynamic pattern of the effects. In this work, we suggest a model that can deal with both fixed and time varying effects and uses simple hypotheses tests to distinguish which covariates do have dynamic effects. The model is an extension of the parsimonious reduced rank model of rank 1. As such, the number of parameters is kept low, and thus, a flexible set of time functions, such as b-splines, can be used. The basic theory is illustrated along with an efficient fitting algorithm. The proposed method is applied to a dataset of breast cancer patients and compared with a multivariate fractional polynomials approach for modelling time-varying effects. Copyright © 2016 John Wiley & Sons, Ltd

Next generation sequencing of chromosomal rearrangements in patients with split-hand/split-foot malformation provides evidence for DYNC1I1 exonic enhancers of DLX5/6 expression in humans

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this recordSplit-hand/foot malformation type 1 is an autosomal dominant condition with reduced penetrance and variable expression. We report three individuals from two families with split-hand/split-foot malformation (SHFM) in whom next generation sequencing was performed to investigate the cause of their phenotype.Wellcome Trus

Clinical and molecular characterization of 17q21.31 microdeletion syndrome in 14 French patients with mental retardation.

International audienceChromosome 17q21.31 microdeletion was one of the first genomic disorders identified by chromosome microarrays. We report here the clinical and molecular characterization of a new series of 14 French patients with this microdeletion syndrome. The most frequent clinical features were hypotonia, developmental delay and facial dysmorphism, but scaphocephaly, prenatal ischemic infarction and perception deafness were also described. Genotyping of the parents showed that the parent from which the abnormality was inherited carried the H2 inversion polymorphism, confirming that the H2 allele is necessary, but not sufficient to generate the 17q21.31 microdeletion. Previously reported molecular analyses of patients with 17q21.31 microdeletion syndrome defined a 493 kb genomic fragment that was deleted in most patients after taking into account frequent copy number variations in normal controls, but the deleted interval was significantly smaller (205 kb) in one of our patients, encompassing only the MAPT, STH and KIAA1267 genes. As this patient presents the classical phenotype of 17q21.31 syndrome, these data make it possible to define a new minimal critical region of 160.8 kb, strengthening the evidence for involvement of the MAPT gene in this syndrome

Polyene Macrolide Antifungal Drugs Trigger Interleukin-1β Secretion by Activating the NLRP3 Inflammasome

The use of antimycotic drugs in fungal infections is based on the concept that they suppress fungal growth by a direct killing effect. However, amphotericin and nystatin have been reported to also trigger interleukin-1β (IL-1β) secretion in monocytes but the molecular mechanism is unknown. Here we report that only the polyene macrolides amphotericin B, nystatin, and natamycin but none of the tested azole antimycotic drugs induce significant IL-1β secretion in-vitro in dendritic cells isolated from C57BL/6 mouse bone marrow. IL-1β release depended on Toll-like receptor-mediated induction of pro-IL-1β as well as the NLRP3 inflammasome, its adaptor ASC, and caspase-1 for enzymatic cleavage of pro-IL-1β into its mature form. All three drugs induced potassium efflux from the cells as a known mechanism for NLRP3 activation but the P2X7 receptor was not required for this process. Natamycin-induced IL-1β secretion also involved phagocytosis, as cathepsin activation as described for crystal-induced IL-1β release. Together, the polyene macrolides amphotericin B, nystatin, and natamycin trigger IL-1β secretion by causing potassium efflux from which activates the NLRP3-ASC-caspase-1. We conclude that beyond their effects on fungal growth, these antifungal drugs directly activate the host's innate immunity