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Trees have evolved strategies to fight enemies and survive during their million-year history. These strategies have been shaped by natural selection and are reflected in their genomes today. Tree planting is a priority for governments, but there is a risk that trees selected by humans will lack alleles important for disease resistance. Norway spruce (Picea abies) is a characteristic species in the Swedish landscape and one of the most important trees for the forest industry. Therefore, the overall aim of this thesis was to study the genetic variation of resistance traits in Norway spruce to Heterobasidion parviporum and Heterobasidion annosum s.s., two fungal pathogens causing root and stem rot in conifers. In the first two papers, the genomic basis of resistance traits was studied with genome-wide association studies (GWAS). Associations between single nucleotide polymorphisms (SNPs) and resistance traits led to the discovery of several variants, with relatively small effects, associated with resistance to each pathogen. Correlation of resistance traits to these two species was dependent on the environment but using GWAS pleiotropic SNPs associated with resistance to both pathogens were found. Synergistic pleiotropic SNPs are genes that could provide multiple disease resistance in trees. In the third paper, signatures of selection in PaLAR3 were studied. This gene is associated with defence against pathogenic fungi in Norway spruce. Genomic analyses demonstrated that variation in PaLAR3 has been likely maintained by balancing selection in Norway spruce. Moreover, it seems that this process started before Norway spruce isolated reproductively from white spruce (Picea glauca). In the fourth paper, resistance in the bark was studied in ten Norway spruce genotypes varying in susceptibility, inoculated with five Heterobasidion isolates varying in virulence. Both host and pathogen influenced the length of lesions in the bark. Using differential gene expression and co-expression networks, it was shown that Norway spruce genotypes with relatively high resistance had a robust response, which included the expression of pathogen recognition genes. In contrast, in a more susceptible host, the response was dependent on the virulence of the H. annosum s.s. isolate. Overall, the thesis advances the knowledge on disease resistance in Norway spruce. This knowledge will support the Swedish Norway spruce breeding program decision making in selecting healthier trees in the future.

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

The surge of information generated by the Human Genome Project has left many health professionals and their patients struggling to understand the role of genetics in health and disease. To aid the lay public and health professionals, the US National Library of Medicine developed an online resource called 'Genetics Home Reference' (GHR), located at http://ghr.nlm.nih.gov/. Launched in April 2003, GHR's goal is to help the public interpret the health implications of the Human Genome Project. It bridges the clinical questions of consumers and the rich technical data emerging from the sequenced human genome. The GHR web site is designed for easy navigation among summaries for genetic conditions and the related gene(s) and chromosome(s). This design strategy enhances the user's appreciation of how genes, chromosomes, and conditions are interrelated.

The emergence of bovine spongiform encephalopathy (BSE) in cattle and, subsequently, its transmission to humans resulting in variant Creutzfeldt-Jakob disease (vCJD) in the UK has proved to be one of the major public health scares of the century. The oral route of infection, the long incubation period, and the incredible resistance of the transmissible infectious agent to various forms of decontamination poses unique challenges. Fortunately, despite extensive exposure of the UK population to contaminated meat, the size of the vCJD epidemic that has emerged since its initial detection is relatively low (225 worldwide). An explanation for this disparity is as yet incomplete, but the development of the disease is likely influenced by a number of factors including physical properties of the infectious agent, environmental factors such as the route and amount of exposure and individual susceptibility factors. This review focuses on current knowledge of the genetic factors that undoubtedly play a major role in influencing the development of vCJD. In terms of genetic susceptibility, the best characterised is the common single nucleotide polymorphism at codon 129 of the human prion protein gene <i>(PRNP)</i>. Moreover, several other polymorphisms and mutations have been identified that may affect susceptibility as well as other important disease characteristics such as the highly variable prion disease incubation period.

Multiple myeloma (MM) is a hematological malignancy caused by the clonal expansion of plasma cells. The incidence of MM worldwide is increasing with greater than 140,000 people being diagnosed with MM per year. While 5-year survival following a diagnosis of MM has improved from 28% in 1975 to 56% in 2012 the disease remains essentially incurable. In this review we summarize our current understanding of MM including its epidemiology, genetics and biology. We will also provide an overview of MM management that have led to improvements in survival, including recent changes to diagnosis and therapies. Areas of unmet need include the management of patients with high-risk MM, those with a reduced performance status and those refractory to standard therapies. Ongoing research into the biology and early detection of MM as well as the development of novel therapies such as immunotherapies have the potential to influence MM practice in the future. This article is protected by copyright. All rights reserved. ; Cancer Research UK (C1298/A8362), Grant/Award Number: C1298/A8362; European Union's Horizon 2020 Research and Innovation Programme, Grant/Award Number: 856620; Royal Marsden Biomedical Research Centre; Myeloma UK; National Institute for Health

Originating in South America, cassava is now grown in over 100 countries around the world. It is the third most important source of calories in the tropics after rice and maize. Its caloric value, as well as its ability to tolerate dry conditions and poor soils, makes it a key food security crop in developing countries, particularly in Africa. As demand for food grows, there is an urgent need to increase yields in the face of such challenges as climate change, threats from pests and diseases and the need to make cultivation more resource-efficient and sustainable. Drawing on an international range of expertise, this collection focuses on ways of improving the cultivation of cassava at each step in the value chain, from breeding to post-harvest storage. Volume 1 starts by reviewing genetic resources, advances in breeding and their application to produce varieties with desirable traits such as higher yield. It then goes on to review developments in understanding and managing pests and diseases. Achieving sustainable cultivation of cassava Volume 2: Genetic resources, breeding, pests and diseases will be a standard reference for agricultural scientists in universities, government and other research centres and companies involved in improving cassava cultivation. It is accompanied by Volume 1 which reviews cultivation techniques.

Copyright © 2021 The Author(s). Drug target Mendelian randomization (MR) studies use DNA sequence variants in or near a gene encoding a drug target, that alter the target's expression or function, as a tool to anticipate the effect of drug action on the same target. Here we apply MR to prioritize drug targets for their causal relevance for coronary heart disease (CHD). The targets are further prioritized using independent replication, co-localization, protein expression profiles and data from the British National Formulary and clinicaltrials.gov. Out of the 341 drug targets identified through their association with blood lipids (HDL-C, LDL-C and triglycerides), we robustly prioritize 30 targets that might elicit beneficial effects in the prevention or treatment of CHD, including NPC1L1 and PCSK9, the targets of drugs used in CHD prevention. We discuss how this approach can be generalized to other targets, disease biomarkers and endpoints to help prioritize and validate targets during the drug development process. ; The authors are grateful to the studies and consortia that provided summary association results and to the participants of the biobanks and research cohorts. This research has been conducted using the UK Biobank Resource under Application Number 12113. UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government, and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government and the British Heart Foundation. M.G.M. is supported by a BHF Fellowship FS/17/70/33482. A.F.S. is supported by BHF grant PG/18/5033837 and the UCL BHF Research Accelerator AA/18/6/34223. C.F. and A.F.S. received additional support from the National Institute for Health Research University College London Hospitals Biomedical Research Centre. A.D.H. is an NIHR Senior Investigator. We further acknowledge support from the Rosetrees Trust. The UCLEB Consortium is supported by a British Heart Foundation Program Grant (RG/10/12/28456). M.K. was supported by grants from the Wellcome Trust, UK (221854/Z/20/Z), the UK Medical Research Council (R024227 and S011676), the National Institute on Aging, NIH (R01AG056477 and RF1AG062553), and the Academy of Finland (311492). AH receives support from the British Heart Foundation, the Economic and Social Research Council (ESRC), the Horizon 2020 Framework Program of the European Union, the National Institute on Aging, the National Institute for Health Research University College London Hospitals Biomedical Research Centre, the UK Medical Research Council and works in a unit that receives support from the UK Medical Research Council. A.G. is funded by the Member States of EMBL. P.C. is supported by the Thailand Research Fund (MRG6280088). D.A.L. is supported by a British Heart Foundation Chair (CH/F/20/90003) and British Heart Foundation grant (AA/18/7/34219), is a National Institute of Health Research Senior Investigator (NF-0616-10102) and works in a Unit that receives support from the University of Bristol and UK Medical Research Council (MC_UU_00011/6). This work was funded in part by the UKRI and NIHR through the Multimorbidity Mechanism and Therapeutics Research Collaborative (MR/V033867/1).

The paper discusses options for disease prevention in Public Health Genetics and attempts to assess the probability that coercive strategies might be chosen in public health policies that impose duties to undergo genetic testing. Given the social values, legal and political cultures and professional orientations in Western Europe and the United States, which provide the terms of reference for this assessment, it is unlikely that the preventive options which might emerge from human genetics in the future will trigger policies that force preventive behavior upon people, except in the cases where such enforcement is designed to protect third parties.