Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Déterminisme génétique de quelques composés biochimiques de la graine de café vert impliqués dans la qualité à la tasse (Etude d'un croisement entre coffea pseudozanguebariae et c.liberica var.dewevrei)

MONTPELLIER-SupAgro La Gaillarde (341722306) / SudocSudocFranceF

Polynesian pearls

Black-lip pearl oyster culture in French Polynesia is still based on natural spat collection from wild stocks, but new developments in hatchery technology and selective breeding are bringing substantive change to the sector

Shell Growth Performance of Hatchery Produced Pinctada margaritifera: Family Effect and Relation with Cultured Pearl Weight

Size is the most important and valuable quality trait of cultured pearls produced by the black-lipped pearl oyster, Pinctada margaritifera. In French Polynesia, several breeding programmes have been started that aim to improve this size trait, which is highly related to shell growth rate in both recipient and donor oysters. Shell growth rate dictates the time of grafting, size of implanted nuclei and bio-mineralisation potential of the mantle and pearl sac. We assessed shell growth rate through routine digital shell biometric analysis on 22 hatchery families produced between 2005 and 2008. These included full-sib families and half-sib families derived from polyandry (one dam crossed with two or more sires). Results showed that: 1) a significant family effect was recorded for growth performance, analysed according to the Von Bertalanffy model, 2) a significant male effect was observed for some of the half-sib families and 3) a relationship was found between the shell growth performances of five families randomly selected and used as graft donors in a grafting experiment and the final weight of the cultured pearls produced. These results have important implications for the breeding of pearl oysters with high growth capacities: it may be possible to select oyster lines for the potential to produce large pearls using shell equivalent diameter estimated by the digital method as a selection criterion

Optimal age of the donor graft tissue in relation to cultured pearl phenotypes in the mollusc, Pinctada margaritifera

Ageing is defined as the progressive decline in tissue and organ functions over time. This study aims to evaluate the ageing effect on cultured pearl quality phenotypes (including size and quality traits) in the graft-recipient animal model: Pinctada margaritifera. For this, eight uniform grafting experiments were designed using two hatchery-produced pearl oyster families as donors, which were followed through time, between 7 and 30 months in age. For each age category, 20 donors were studied for each culture site giving a total of 2400 grafted oysters. Several phenotypic measurements were made: 1) donor family growth performance from shell size records, 2) pearl size and corresponding quality traits, and 3) expression of some genes related to biomineralization processes on both the mantle graft and on pearl sac tissues. Results showed that: 1) donor age has an impact on pearl size, with grafts coming from the youngest donors yielding the biggest pearls; and 2) grafts from donors between 12 and 18 months in age produced pearls of the highest quality (grade and surface quality), a result supported by an analysis where the level of expression for a panel of genes associated with biomineralization was greatest in donors within the 12 to 18 months age group. These results indicate that donors aged between 12 and 18 months have high potential for biomineralisation and nacre deposition, and likely produce larger and higher quality cultured pearls than older donors

Genetic investigations on the caffeine and chlorogenic acid relationship in an interspecific cross between Coffea liberica dewevrei and C-pseudozanguebariae

International audienceThe objective of the paper was to identify the number of major loci explaining caffeine content in coffee seeds. Investigations were based on previously published results: (1) Caffeine binds to chlorogenic acids in a 1:1 molecular ratio; (2) Between species, the caffeine content is correlated to the chlorogenic acid content; (3) Only a part of chlorogenic acids is bound to caffeine. Especially, the content ratio between caffeine and chlorogenic acids varied between species. For identifying the number of major loci, a quantitative trait locus (QTL) approach was carried out using an interspecific cross between two highly differentiated species-Coffea liberica dewevrei and Coffea pseudozanguebariae, the latter being a caffeine-free species. As main finding, two QTLs, i.e., RCQ1 and CQA1, were identified allowing us to explain up to 97 % of the caffeine content variance. RCQ1 explained variation of the caffeine/chlorogenic acid ratio and was genetically independent of the second QTL. The latter explained the part of the caffeine content which was dependent on the chlorogenic acid content. The findings also confirmed that only a part of chlorogenic acids were trapped by caffeine, as in wild species

Cultured Pearl Surface Quality Profiling by the Shell Matrix Protein Gene Expression in the Biomineralised Pearl Sac Tissue of Pinctada margaritifera

Nucleated pearls are produced by molluscs of the Pinctada genus through the biomineralisation activity of the pearl sac tissue within the recipient oyster. The pearl sac originates from graft tissue taken from the donor oyster mantle and its functioning is crucial in determining key factors that impact pearl quality surface characteristics. The specific role of related gene regulation during gem biogenesis was unknown, so we analysed the expression profiles of eight genes encoding nacreous (PIF, MSI60, PERL1) or prismatic (SHEM5, PRISM, ASP, SHEM9) shell matrix proteins or both (CALC1) in the pearl sac (N = 211) of Pinctada margaritifera during pearl biogenesis. The pearls and pearl sacs analysed were from a uniform experimental graft with sequential harvests at 3, 6 and 9 months post-grafting. Quality traits of the corresponding pearls were recorded: surface defects, surface deposits and overall quality grade. Results showed that (1) the first 3 months of culture seem crucial for pearl quality surface determination and (2) all the genes (SHEM5, PRISM, ASP, SHEM9) encoding proteins related to calcite layer formation were over-expressed in the pearl sacs that produced low pearl surface quality. Multivariate regression tree building clearly identified three genes implicated in pearl surface quality, SHEM9, ASP and PIF. SHEM9 and ASP were clearly implicated in low pearl quality, whereas PIF was implicated in high quality. Results could be used as biomarkers for genetic improvement of P. margaritifera pearl quality and constitute a novel perspective to understanding the molecular mechanism of pearl formation

Comparison of five purification methods for chlorogenic acids in green coffee beans (Coffea sp.)

La détermination des teneurs en acides chlorogéniques au sein de grandes populations de grains verts de café nécessite une méthode de purification précise, rapide et non-biaisée. Cinq protocoles différents de purification ont été comparés. La première consistait à utiliser successivement différents solvants organiques, la seconde est basée sur la filtration au travers d'une cartouche C18, la troisième utilisait l'action combinée de deux réactifs, et les deux dernières méthodes (4 et 5) étaient une simplification de la troisième. L'une des deux plus simples méthodes de purification (méthode 4) s'est révélée être la plus rapide, la plus précise et la moins biaisée. Par conséquent, cette méthode pourrait être utilisée en routine afin de quantifier les acides chlorogéniques dans les grains verts de café. (Résumé d'auteur

Crossing phenotype heritability and candidate gene expression in grafted black-lipped pearl oyster Pinctada margaritifera, an animal chimera

Grafting mantle tissue of a donor pearl oyster into the gonad of a recipient oyster results in the formation of a chimera, the pearl sac. The phenotypic variations of this chimera are hypothesized to be the result of interactions between the donor and recipient genomes. In this study, the heritability of phenotypic variation and its association with gene expression were investigated for the first time during P. margaritifera pearl production. Genetic variance was evaluated at different levels, 1) before the graft operation (expression in graft tissue), 2) after grafting (pearl sac tissue expression in chimera) and 3) on the product of the graft (pearl phenotype traits) based on controlled bi-parental crosses and the F1 generation. Donor related genetic parameter estimates clearly demonstrate heritability for nacre weight and thickness, darkness and colour, surface defects and grade, which signifies a genetic basis in the donor oyster. In graft relative gene expression, the value of heritability was superior to 0.20 in for almost all genes, while in pearl sac, heritability estimates were low (h² < 0.10) (except for CALC1 and Aspein). Pearl sac expression seems to be more influenced by residual variance than the graft, which can be explained by environmental effects that influence pearls sac gene expression and act as a recipient additive genetic component. The interactions between donor and recipient are very complex and further research is required to understand the role of the recipient oysters on pearl phenotypic and gene expression variances