Identification of novel APOB mutations by targeted next-generation sequencing for the molecular diagnosis of familial hypobetalipoproteinemia

International audienceFamilial hypobetalipoproteinemia (FHBL) is a co-dominant disorder characterized by decreased plasma levels of LDL-cholesterol and apolipoprotein B (ApoB). Currently, genetic diagnosis in FHBL relies largely on Sanger sequencing to identify APOB and PCSK9 gene mutations and on western blotting to detect truncated ApoB species

Variants in the GPR146 Gene Are Associated With a Favorable Cardiometabolic Risk Profile

BACKGROUND: In mice, GPR146 (G-protein-coupled receptor 146) deficiency reduces plasma lipids and protects against atherosclerosis. Whether these findings translate to humans is unknown. METHODS: Common and rare genetic variants in the GPR146 gene locus were used as research instruments in the UK-Biobank. The Lifelines, and The Copenhagen-City Heart Study, and a cohort of individuals with familial hypobetalipoproteinemia were used to find and study rare GPR146 variants. RESULTS: In the UK-Biobank, carriers of the common rs2362529-C allele present with lower low-density lipoprotein cholesterol, apo (apolipoprotein) B, high-density lipoprotein cholesterol, apoAI, CRP (C-reactive protein), and plasma liver enzymes compared with noncarriers. Carriers of the common rs1997243-G allele, associated with higher GPR146 expression, present with the exact opposite phenotype. The associations with plasma lipids of the above alleles are allele dose-dependent. Heterozygote carriers of a rare coding variant (p.Pro62Leu; n=2615), predicted to be damaging, show a stronger reductions in the above parameters compared with carriers of the common rs2362529-C allele. The p.Pro62Leu variant is furthermore shown to segregate with low low-density lipoprotein cholesterol in a family with familial hypobetalipoproteinemia. Compared with controls, carriers of the common rs2362529-C allele show a marginally reduced risk of coronary artery disease (P=0.03) concomitant with a small effect size on low-density lipoprotein cholesterol (average decrease of 2.24 mg/dL in homozygotes) of this variant. Finally, mendelian randomization analyses suggest a causal relationship between GPR146 gene expression and plasma lipid and liver enzyme levels. CONCLUSIONS: This study shows that carriers of new genetic GPR146 variants have a beneficial cardiometabolic risk profile, but it remains to be shown whether genetic or pharmaceutical inhibition of GPR146 protects against atherosclerosis in humans

Les techniques et la très longue durée : réflexions croisées

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Biodiversité dans différents compartiments du Trias traversés par le forage ANDRA à 2000 mètres dans le Mésozoïque du Bassin de Paris

Longtemps considérées comme stériles, les roches sédimentaires profondes sont maintenant connues pour renfermer une part significative de biomasse bactérienne. Malgré les récentes avancées dans le domaine de la géomicrobiologie, la composition, la distribution et l'organisation microbienne des écosystèmes terrestres profonds restent encore mal connues. Ces environnements constituent d'importants réservoirs microbiologiques inexplorés et inexploités et il apparaît pertinent, voire stratégique, d'étudier activement le sous-sol terrestre, afin de rechercher l'éventuelle présence de vie microbienne, d'identifier la diversité de sa fonctionnalité dans le but d'aboutir à une meilleure compréhension des cycles biogéochimiques dans de tels écosystèmes. En 2008, l'étude de la zone de transposition du laboratoire souterrain de Meuse/Haute Marne (ANDRA) a nécessité la réalisation d'un forage allant jusqu'au Trias (-2000m) offrant un accès direct et privilégié à différents faciès géologiques extraits le long d'une gamme de profondeur étendue. Nos travaux ont porté sur quatre carottes issues du Trias et collectées entre 1725 et 1960 mètres de profondeur, avec pour but de caractériser la microflore bactérienne colonisant ces roches, par des approches complémentaires : culturales et moléculaires. Malgré la recherche de plusieurs métabolismes connus pour exister dans les écosystèmes profonds ainsi que l'application de conditions de cultures variées incluant l'application des conditions in situ en termes de température et de pression, il n'a pas été possible de détecter une microflore bactérienne cultivable dans ces roches. Par contre , en ce qui concerne les approches moléculaires, après extraction directe de l'ADN génomique total, des études comparatives basées sur la diversité du gène codant l'ARNr 16S, marqueur moléculaire universel du monde bactérien, ont permis de détecter la présence d'une communauté bactérienne complexe dans différentes matrices de roches. La détection moléculaire d'une microflore bactérienne dans les roches profondes du Trias, son caractère autochtone ou allochtone, notre incapacité à en cultiver les représentants ainsi que les perspectives d'études de tels écosystèmes extrêmes seront discutés

Prevalence of Hypobetalipoproteinemia and Related Psychiatric Characteristics in a Psychiatric Population: Results from the Retrospective HYPOPSY Study

International audienceBACKGROUND: Hypobetalipoproteinemia (HBL) is defined by plasma concentrations of LDL-cholesterol (LDL-C) lower than the fifth percentile for age and sex. Several psychiatric symptoms have been reported in association with HBL. The objective was to assess the prevalence of primary HBL in patients hospitalized in a psychiatric population and to better characterize the related psychiatric disorders. METHODS: HYPOPSY is a retrospective study including 839 adults hospitalized in the Psychiatry department of Nantes University Hospital during the year 2014, except patients with eating disorders. The prevalence of primary HBL was defined by a plasma LDL-C concentration ≤q 50 mg/dL. Secondary causes of HBL were excluded after a review of medical records (n=2). Related-psychiatric disorders in patients with and without HBL were recorded using the ICD-10 classification. RESULTS: Twenty cases of primary HBL (mean [SD] LDL-C: 42 [7] mg/dL) were diagnosed, leading to a prevalence of 2.39%. In comparison, the prevalence of HBL in a healthy control population was 0.57%. Psychiatric patients with HBL were characterized by a higher frequency of schizophrenia (p=0.044), hetero-aggression (p=0.015) and pervasive and specific developmental disorders (including autism)~(p=0.011). CONCLUSIONS: The prevalence of HBL is 4-fold higher in psychiatric than in general population. More specifically, some statistically significant associations were found between low LDL-C concentrations and schizophrenia, autism and hetero-aggression. These data reinforce the hypothesis for a link between genetically low LDL-C levels and psychiatric disorders

Automatic recognition of flow cytometric phytoplankton functional groups using convolutional neural networks

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Uranium interactions with bacterial communities from contaminated soils in Chernobyl

Following the Chernobyl accident in 1986, vegetation, contaminated soil and other radioactive debris were shortly buried in situ in trenches. The present work describes the analysis of the structure of the bacterial communities that have been evolving in this environment for more than 20 years. Comparison of the diversities found in soil samples exhibiting contrasted radionuclides content is a prerequesite to point out the potential role of microorganisms in radionuclide migration in soils

Standard vocabulary, consensual functional groups and automated classification for phytoplankton high throughput datasets using automated flow cytometry

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The Staphylococci phages family: an overview.

Due to their crucial role in pathogenesis and virulence, phages of Staphylococcus aureus have been extensively studied. Most of them encode and disseminate potent staphylococcal virulence factors. In addition, their movements contribute to the extraordinary versatility and adaptability of this prominent pathogen by improving genome plasticity. In addition to S. aureus, phages from coagulase-negative Staphylococci (CoNS) are gaining increasing interest. Some of these species, such as S. epidermidis, cause nosocomial infections and are therefore problematic for public health. This review provides an overview of the staphylococcal phages family extended to CoNS phages. At the morphological level, all these phages characterized so far belong to the Caudovirales order and are mainly temperate Siphoviridae. At the molecular level, comparative genomics revealed an extensive mosaicism, with genes organized into functional modules that are frequently exchanged between phages. Evolutionary relationships within this family, as well as with other families, have been highlighted. All these aspects are of crucial importance for our understanding of evolution and emergence of pathogens among bacterial species such as Staphylococci.Journal ArticleResearch Support, Non-U.S. Gov'tReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe