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Mutated TP53 is a marker of increased VEGF expression: analysis of 7,525 pan-cancer tissues.
Anti-angiogenic therapies are an important class of anti-cancer treatment drugs. However, their efficacy is limited to certain tumors and would benefit from identifying a biomarker predictive of therapeutic response. TP53 (tumor protein p53) is a tumor suppressor gene frequently mutated in cancer and implicated in cell-cycle regulation, apoptosis, and angiogenesis. Data from 7,525 unique tumor samples (representing 30 tumor cohorts) were retrieved from the TCGA database to analyze the relationship between TP53-mutation status and VEGFA (vascular endothelial growth factor A) expression. Univariate analyses were done using a Mann-Whitney univariate test or Fisher's exact test. Parameters with a p-value (p)â€0.1 in univariate analysis were selected for follow-up multivariate analyses, including TP53-mutation status, cancer cohorts, cancer subtypes, and VEGFA expression. Our analysis demonstrates statistically significant increases in VEGFA mRNA tissue expression in TP53-mutated adenocarcinomas (but not in squamous cancers) compared to TP53 wild-type tumors. This association holds true in multivariate analyses and remains independent of HIF-1α and MDM2 overexpression. Our findings provide additional evidence that TP53 mutations are linked to the VEGF pathway, potentially offering insight into the mechanism behind increased sensitivity to anti-angiogenic therapies observed in some TP53-mutant tumors
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
Nomenclature for naming loci, alleles, linkage groups and chromosomes to be used in poultry genome publications and databases
International audienc
Approximate restricted maximum likelihood and approximate prediction error variance of the Mendelian sampling effect
In an Expectation-Maximization type Restricted Maximum Likelihood (REML) procedure, the estimation of a genetic (co-)variance component involves the trace of the product of the inverse of the coefficient matrix by the inverse of the relationship matrix. Computation of this trace is usually the limiting factor of this procedure. In this paper, a method is presented to approximate this trace in the case of an animal model, by using an equivalent model based on the Mendelian sampling effect and by simplifying its coefficient matrix and its inversion. This approximation appeared very accurate for low heritabilities but was downwards biased when the heritability was high. Implemented in a REML procedure, this approximation reduced dramatically the amount of computation, but provided downwards biased estimates of genetic variances. Several examples are presented to illustrate the method.Dans certaines procĂ©dures de Maximum de Vraisemblance Restreint (REML), lâestimation des composantes de (co)variance gĂ©nĂ©tique implique le calcul de la trace du produit de lâinverse de la matrice des coefficients par lâinverse de la matrice de parentĂ©s, calcul qui constitue gĂ©nĂ©ralement le facteur limitant de ce type de procĂ©dure. Nous prĂ©sentons dans cet article une mĂ©thode visant Ă obtenir une valeur approchĂ©e de cette trace dans le cadre dâun modĂšle animal, en utilisant un modĂšle Ă©quivalent basĂ© sur lâalĂ©a de mĂ©iose, en simplifiant sa matrice des coefficients et en en calculant une inverse approchĂ©e. Cette approximation est trĂšs prĂ©cise lorsque lâhĂ©ritabilitĂ© du caractĂšre est faible mais elle tend Ă sous-estimer la trace vraie lorsque lâhĂ©ritabilitĂ© est Ă©levĂ©e. IntĂ©grĂ©e dans une procĂ©dure de REML, cette mĂ©thode en rĂ©duit considĂ©rablement le coĂ»t mais fournit en gĂ©nĂ©ral des valeurs sous-estimĂ©es de variance gĂ©nĂ©tique. Divers exemples sont prĂ©sentĂ©s Ă titre d'illustratio
A criterion for measuring the degree of connectedness in linear models of genetic evaluation
International audienc
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