Germline TP53 mutations result into a constitutive defect of p53 DNA binding and transcriptional response to DNA damage

International audienc

How did the dipole axis vary during the first millennium BCE? New data from West Europe and analysis of the directional global database

International audienceDespite progress in the knowledge of secular variation during the first millennium BCE in Europe, data coverage remains poor at the earliest periods, especially in some regions as in the Central Mediterranean area. This study presents three new directional and six new intensity data between the 13th and the 4th centuries BCE on archaeological kilns, pottery and baked clay fragments from South Italy and France. Archaeodirections were determined after thermal demagnetizations and archaeointensities using the Thellier-Thellier protocol with corrections for the anisotropy and cooling rate effects. The new data confirm the large deviation of the direction from a Geocentric Axial Dipole field, the high geomagnetic field strength and the fast secular variation observed in Europe during the earliest half of the first millennium BCE. Another characteristic of this period is a difference of ~25° between the longitudes of the virtual geomagnetic poles inferred from European and Middle East data. This unusual behaviour can be mainly related to the Levantine Iron Age anomaly (LIAA) and its expansion from the Middle East to Europe. However, the review of the global directional database shows that almost all virtual geomagnetic poles, 96% of them coming from Europe, the Middle East, East Asia, North America and Hawaii, are 10–25° away from the rotation axis towards North Russia between 1000 and 600 BCE. The calculation of a mean global VGP curve suggests that the North geomagnetic pole followed a clockwise motion during this period with a dipole tilt up to around 14°. This study shows that a dipole axis tilt may have played an important role in the rapid secular variation in western Eurasia, although part of this variation may also be related to non-dipole fields associated with the LIAA

Blood functional assay for rapid clinical interpretation of germline TP53 variants

International audienceThe interpretation of germline TP53 variants is critical to ensure appropriate medical management of patients with cancer and follow-up of variant carriers. This interpretation remains complex and is becoming a growing challenge considering the exponential increase in TP53 tests. We developed a functional assay directly performed on patients' blood

Optimization of the diagnosis of inherited colorectal cancer using NGS and capture of exonic and intronic sequences of panel genes

International audienc

Metabolic causes of nonimmune hydrops fetalis: A next-generation sequencing panel as a first-line investigation.

International audienceHydrops fetalis is a life-threatening fetal condition, and 85% of all cases are classified as nonimmune hydrops fetalis (NIHF). Up to 15% of NIHF cases may be due to inborn errors of metabolism (IEM), but a large proportion of cases linked to metabolic disorders remains undiagnosed. This lack of diagnosis may be related to the limitations of conventional biological procedures, which involve sequential investigations and require multiple samples and steps. In addition, this approach is time consuming. We have developed a next-generation sequencing (NGS) panel to investigate metabolic causes of NIHF, ascites, and polyhydramnios associated to another fetal abnormality

Assessment of branch point prediction tools to predict physiological branch points and their alteration by variants

International audienceAbstract Background Branch points (BPs) map within short motifs upstream of acceptor splice sites (3’ss) and are essential for splicing of pre-mature mRNA. Several BP-dedicated bioinformatics tools, including HSF, SVM-BPfinder, BPP, Branchpointer, LaBranchoR and RNABPS were developed during the last decade. Here, we evaluated their capability to detect the position of BPs, and also to predict the impact on splicing of variants occurring upstream of 3’ss. Results We used a large set of constitutive and alternative human 3’ss collected from Ensembl ( n = 264,787 3’ss) and from in-house RNAseq experiments ( n = 51,986 3’ss). We also gathered an unprecedented collection of functional splicing data for 120 variants (62 unpublished) occurring in BP areas of disease-causing genes. Branchpointer showed the best performance to detect the relevant BPs upstream of constitutive and alternative 3’ss (99.48 and 65.84% accuracies, respectively). For variants occurring in a BP area, BPP emerged as having the best performance to predict effects on mRNA splicing, with an accuracy of 89.17%. Conclusions Our investigations revealed that Branchpointer was optimal to detect BPs upstream of 3’ss, and that BPP was most relevant to predict splicing alteration due to variants in the BP area

Optimization of the diagnosis of inherited colorectal cancer using NGS and capture of exonic and intronic sequences of panel genes

International audienc