Models for Prediction of Factor VIII Half-Life in Severe Haemophiliacs: Distinct Approaches for Blood Group O and Non-O Patients

BACKGROUND: Von Willebrand factor (VWF) is critical for the in vivo survival of factor VIII (FVIII). Since FVIII half-life correlates with VWF-antigen pre-infusion levels, we hypothesized that VWF levels are useful to predict FVIII half-life. METHODOLOGY: Standardized half-life studies and analysis of pre-infusion VWF and VWF-propeptide levels were performed in a cohort of 38 patients with severe haemophilia A (FVIII <1 IU/ml), aged 15-44 years. Nineteen patients had blood-group O. Using multivariate linear regression-analysis (MVLR-analysis), the association of VWF-antigen, VWF-propeptide, age and body-weight with FVIII half-life was evaluated. PRINCIPAL FINDINGS: FVIII half-life was shorter in blood-group O-patients compared to non-O-patients (11.5+/-2.6 h versus 14.3+/-3.0 h; p = 0.004). VWF-antigen levels correlated with FVIII half-life considerably better in patients with blood-group non-O than O (Pearson-rank = 0.70 and 0.47, respectively). Separate prediction models evolved from MVLR-analysis for blood-group O and non-O patients, based on VWF-antigen and VWF/propeptide ratio. Predicted half-lives deviated less than 3 h of observed half-life in 34/38 patients (89%) or less than 20% in 31/38 patients (82%). CONCLUSION: Our approach may identify patients with shorter FVIII half-lives, and adapt treatment protocols when half-life studies are unavailable. In addition, our data indicate that survival of FVIII is determined by survival of endogenous VWF rather than VWF levels per se

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WHEALBI: Wheat and barley legacy for breeding improvement; A EU-FP7 Project to link genomics and agronomy

Book of abstracts p. 203WHEALBI is granted 5 M€ by EU-FP7 (Grant no 613 556) for 5 years starting January, 2014.It involves 18 partners (8 academics, 7 industry /SME) in 9 countries and aims at improvingEuropean wheat and barley production in competitive and sustainable cropping systems.Germplasm will be selected and characterised by next-generation-sequencing. Adaptive traitswill be evaluated in both transnational field experiments and precision phenotyping platforms.Germplasm will be stored in a bio-repository and associated data in knowledge bases that willrepresent a valuable legacy to the community. Whole genome association scans will beconducted for several traits, signatures of adaptive selection will be explored, and allelemining of candidate genes will reveal new variation associated with specific phenotypes. Prebreedingtools will be developed to optimize the efficiency of allele transfer from unadaptedgermplasm into elite breeding lines. New methodologies will explore how to optimally exploitthe large amount of new genotypic and phenotypic data available. Ideotypes with improvedyield stability and tolerance to biotic and climatic stresses will be evaluated in innovativecropping systems, particularly organic farming and no-till agriculture, and an economicevaluation will be conducted. Results will be disseminated to a broad user community,highlighting the benefits and issues associated with the adoption of sustainable wheat andbarley crop production.In 2015, WHEALBI has produced significant achievements in several ways. First of all,exome sequence of 512 barley and 512 wheat accessions covering the range of geneticdiversity have been produced. These raw data are currently being processed (cleaning, qualitycontrol, SNP calling) to be released to WHEALBI partners in early 2016. As an evidence ofthe value of these data, we already received demands from several consortia to have access,which will be effective soon after first exploitation within WHEALBI. These 1024 accessionshave also been planted in the field, at 7 locations for each species, spanning over Europe fromScotland to Turkey. This will allow a comprehensive study of adaptation to a wide range ofclimatic conditions, and exome data will give insights into its genetic components.In 2016, exome polymorphism will also be “mined” to explore the genetic bases of keyadaptive traits, and used in statistical models to improve genetic dissection breedingefficiency, as illustrated by the 1000 bulls genome project(http://www.1000bullgenomes.com). A smaller collection of diverse barley and wheatvarieties will also be studied in innovative, more sustainable cropping systems, includingorganic, to anticipate the needs of future European Agriculture

WHEALBI: Wheat and barley legacy for breeding improvement; A EU-FP7 Project to link genomics and agronomy

Book of abstracts, p. 108WHEALBI: Wheat and barley legacy for breeding improvement; A EU-FP7 Project to link genomics and agronomy. Recent progress in drought tolerance: from genetics to modellin