Title Participants "Genetic testing in asymptomatic minors: recommendations of the European Society of Human Genetics Recommendations of the European Society of Human Genetics" "Pascal Borry, Kris Dierickx" "Genetic Counselling in Belgium: the Centre for Human Genetics at the University of Leuven, 1960-1990" "Joris Vandendriessche" "© Springer International Publishing AG 2017. All rights reserved. This chapter traces the history of the Center for Human Genetics (CHG)- the first centre of this kind in Belgium-at the University of Leuven from the 1960s to the 1990s. In 1960, a laboratory for diagnostic chromosomal research was set up by the physician and geneticist Herman Van den Berghe. In 1966, this laboratory was turned into the Center for Human Genetics (CHG), which combined a service of genetic counselling with genetic research. The paper discusses the evolution of the Leuven CHG in relation to developments within the Faculty of Medicine and the University of Leuven, to government policies on genetics and to wider social debates. The CHG's expansion in the 1970s, 1980s and 1990s was paralleled by governmental attention to the field of human genetics and the life sciences. State support was allocated to eight genetic centres, which-following the Leuven model-were integrated into the Belgian academic hospitals, resulting in a decentralised model. This system of financing contributed, it will be shown, to the multidisciplinary nature of genetic research and counselling in Belgium. The paper also pays attention to contemporary ethical debates about medical technologies, of which genetic diagnoses were part. While these debates were conducted nationwide, they were particularly present at the University of Leuven, as the institution struggled to reconcile its Catholic heritage with its modern research ambitions." "Gene Prioritization Through Genomic Data Fusion: Methods and Applications in Human Genetics (Gen prioritizatie via genomische data fusie: Methodes en toepassingen in menselijke genetica)" "Léon-Charles Tranchevent" "Unravelling the molecular basis underlying genetic disorders is crucial in order to develop effective treatments to tackle these diseases. For many years, scientists have explored which genetic factors were associated with several human traits and diseases. After the completion of the human genome project, several high-throughput technologies have been designed and widely used, therefore producing large amounts of genomic data. At the same time, computational tools have been developed and used in conjunction with wet-lab tools to analyze this data in order to enrich our knowledge of genetics and biology.The main focus of this thesis is gene prioritization, that can be defined as the identification of the most promising genes among a list of candidate genes with respect to a biological process of interest. It is a problem for which large quantities of data have to be manipulated, which typically means that it has to be done in silico. This thesis describes two gene prioritization methods from their theoretical development to their applications to real biological questions.The first part of this thesis describes the development of two data fusion algorithms for gene prioritization respectively based on order statistics and kernel methods. These algorithms have been developed for human and also for reference organisms. Ultimately, a cross-species version of these algorithms have been developed and implemented. Integrating genomic data among closely related organisms is relevant since many researchers are studying human indirectly through the study of reference organisms such as mouse or rat, and are therefore producing mouse/rat specific data, that is still relevant in human biology. Our method can integrate more than 20 distinct genomic data sources for five organisms and is therefore one of the first cross-species gene prioritization method of that scale.Only a fragment of all the computational tools developed each year specifically for biology are still maintained after three years, and even less are used by independent researchers. The second part of this thesis focuses on the benchmarks of the proposed methods, the development of the corresponding web based softwares, and on their application to real biological questions. By making our methods publicly available, we make sure that interested users can apply them for their own problems. In addition, benchmarking is needed to prove that the approach is theoretically valid and can estimate how accurate are the predictions. Ultimately, the inclusion of our computational method within wet-lab workflows show the real usefulness of the approach." "Statement of the ESHG on direct-to-consumer genetic testing for health-related purposes European Society of Human Genetics" "Pascal Borry" "Many private companies offer direct-to-consumer (DTC) genetic testing services. Some tests may detect severe and highly penetrant monogenic disorders, while other tests are for genetic variants found associated with increased susceptibility for common and complex diseases in large-scale population studies. Through its Public and Professional Policy committee followed by member and expert consultation, the European Society of Human Genetics has developed the following policy on advertising and provision of predictive genetic tests by such DTC companies: (1) clinical utility of a genetic test shall be an essential criterion for deciding to offer this test to a person or a group of persons; (2) laboratories providing genetic tests should comply with accepted quality standards, including those regarding laboratory personnel qualifications; (3) information about the purpose and appropriateness of testing should be given before the test is done; (4) genetic counselling appropriate to the type of test and disease should be offered; and for some tests psychosocial evaluation and follow-up should be available; (5) privacy and confidentiality of sensitive genetic information should be secured and the data safely guarded; (6) special measures should be taken to avoid inappropriate testing of minors and other legally incapacitated persons; (7) all claims regarding genetic tests should be transparent; advertisement should be unbiased and marketing of genetic tests should be fair; (8) in biomedical research, health care and marketing, respect should be given to relevant ethical principles, as well as international treaties and recommendations regarding genetic testing; and (9) nationally approved guidelines considering all the above-mentioned aspects should be made and followed. European Journal of Human Genetics (2010) 18, 1271-1273; doi: 10.1038/ejhg.2010.129; published online 25 August 2010" "Human Genetics Society of Australasia Position Statement: Predictive and Presymptomatic Genetic Testing in Adults and Children" "Danya Vears, Samantha Ayres, Jackie Boyle, Julia Mansour, Ainsley J Newson" "In 2020, the Human Genetics Society of Australasia released its Position Statement on Predictive and Presymptomatic Genetic Testing in Adults and Children. This Position Statement synthesizes the major practical, psychosocial and ethical considerations associated with presymptomatic and predictive genetic testing in adults who have the capacity to make a decision, children and young people who lack capacity and adults living with reduced or fluctuating capacity. Recommendations include that predictive testing in adults, young people and children should only be offered with pretest genetic counseling and the option of posttest genetic counseling. An individual considering (for themselves or on behalf of another) whether to have a predictive test should also be supported to allow them to make an autonomous and informed decision. Predictive testing should only be offered to children and young people for conditions where there is likely to be a direct medical benefit to them through surveillance, use of prevention strategies or other medical interventions in the immediate future. Where symptoms are likely to develop in childhood, in the absence of options to implement surveillance or risk reduction measures, genetic health professionals and parents/guardians should discuss whether undertaking predictive testing is the best course of action for the child and the family as a whole. Where symptoms are likely to develop in adulthood, the default position should be to postpone predictive testing until the young person achieves the capacity to make their own autonomous and informed decision." "Human Genetics Society of Australasia Position Statement: Genetic Carrier Testing for Recessive Conditions" "Danya Vears" "This Position Statement provides guidelines to assist all health professionals who receive requests for carrier testing and laboratory staff conducting the tests.In this Statement, the term 'carrier testing' refers to genetic testing in an individual to determine whether they have inherited a pathogenic variant associated with an autosomal or X-linked recessive condition previously identified in a blood relative. Carrier testing recommendations: (1) Carrier testing should only be performed with the individual's knowledge and consent; (2) An individual considering (for themselves, or on behalf of another) whether to have a carrier test should be supported to make an informed decision; (3) The mode of inheritance, the individual's personal experience with the condition, and the healthcare setting in which the test is being performed should be considered when determining whether carrier testing should be offered by a genetic health professional. Regarding children and young people: Unless there is direct medical benefit in the immediate future, the default position should be to postpone carrier testing until the child or young person can be supported to make an informed decision. There may be some specific situations where it is appropriate to facilitate carrier testing in children and young people (see section in this article). In such cases, testing should only be offered with pre- and post-test genetic counseling in which genetic health professionals and parents/guardians should explore the rationale for testing and the interests of the child and the family." "Patenting and licensing in genetic testing - Recommendations of the European Society of Human Genetics (vol 16, pg 405, 2008)" "Segolene Ayme, Gert Matthijs, Violetta Anastasiadou, Fatmahan Atalar, Suzanne Braga, John Burn, Jean-Jacques Cassiman, Martina Cornel, Domenico Coviello, Gerry Kiebooms, Philippe Gorry, Shirley Hodgson, Helena Kaariainen, Gyoergy Kosztolanyi, Ulf Kristoffersson, Milan Macek, Christine Patch, Joerg Schmidtke, Jorge Sequeiros, Dominique Stoppa-Lyonnet, Lisbeth Tranebjaerg, Veronica van Heyningen, Gert-Jan van Ommen" "Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policyEuropean Society of Human Genetics and European Society of Human Reproduction and Embryology" "Pascal Borry, Joris Vermeesch" "In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005." "Unifying Viral Genetics and Human Transportation Data to Predict the Global Transmission Dynamics of Human Influenza H3N2" "Philippe Lemey, Filip Bielejec, Guy Baele" "Information on global human movement patterns is central to spatial epidemiological models used to predict the behavior of influenza and other infectious diseases. Yet it remains difficult to test which modes of dispersal drive pathogen spread at various geographic scales using standard epidemiological data alone. Evolutionary analyses of pathogen genome sequences increasingly provide insights into the spatial dynamics of influenza viruses, but to date they have largely neglected the wealth of information on human mobility, mainly because no statistical framework exists within which viral gene sequences and empirical data on host movement can be combined. Here, we address this problem by applying a phylogeographic approach to elucidate the global spread of human influenza subtype H3N2 and assess its ability to predict the spatial spread of human influenza A viruses worldwide. Using a framework that estimates the migration history of human influenza while simultaneously testing and quantifying a range of potential predictive variables of spatial spread, we show that the global dynamics of influenza H3N2 are driven by air passenger flows, whereas at more local scales spread is also determined by processes that correlate with geographic distance. Our analyses further confirm a central role for mainland China and Southeast Asia in maintaining a source population for global influenza diversity. By comparing model output with the known pandemic expansion of H1N1 during 2009, we demonstrate that predictions of influenza spatial spread are most accurate when data on human mobility and viral evolution are integrated. In conclusion, the global dynamics of influenza viruses are best explained by combining human mobility data with the spatial information inherent in sampled viral genomes. The integrated approach introduced here offers great potential for epidemiological surveillance through phylogeographic reconstructions and for improving predictive models of disease control." "Textbook of Human Reproductive Genetics" "Genetic advances in the reproductive sciences are arguably occurring with greater rapidity than that of any other organ system. Not only have the dazzling technological advances of molecular genetics become applicable in reproduction, but meteoric advances are occurring in diagnosis and treatment. Assisted reproductive technology (ART) has rendered infertility far less daunting. Yet treating such couples, that once would not have conceived, may generate offspring who differ from the general population. Textbook of Human Reproductive Genetics addresses pivotal topics of clinical and scientific interest. There is much for the student, practicing physician, and laboratory scientist alike. Crisply edited by renown geneticists of international repute - Stephane Viville and Karen Sermon - the book begins with a précis of genetic principles - molecular, single gene, and cytogenetic. The novice quickly gets up to speed. The basic science landscape targets fields of most immediate relevance to reproduction. Techniques suitable for analyzing a single cell are explained, one cell's (6 picograms (pg)) DNA obviously necessitates different approaches than if larger amounts of DNA were available. Thus, Kumar et al. explain where we are now and where we will soon be (microarrays and next generation sequencing). Traeger-Synodinos and Staessen cover clinical preimplantation genetic diagnosis. Cell division and the consequences of its perturbation are framed, respectively, by Eichenlaub-Ritter in her chapter on meiosis and by Baart and Van Opstal in their chapter on the role of aneuploidy in human embryonic development. Yatsenko and Rajkovic extend the dialogue to cytogenetic disorders affecting infertility. Monogenic causes are not neglected, Liebaers and colleagues covering infertility in pleiotropic presentation. This is especially relevant because it has become clear that common conditions like premature ovarian failure or polycystic ovarian syndrome are heterogeneous. Thus, looking at rare genes whose perturbations cause syndromes could be a fruitful strategy in identifying more common disorders like premature ovarian failure. Van Monfoort covers epigenetic phenomena as related specifically to ART. The basic science component of this text also lets us know that genes must be expressed, without which it matters little whether they are present or absent. To this end, Balakrishnan and Chaillet discuss transgenerational effects medicated by epigenetic alteration. Fauque and Bourc'his shed light on transposons as newly appreciated determinants of male reproductive fitness. The scientific framework having been established, specific clinical aspects of human reproduction are then systematically addressed. Individualized ART tests are discussed by Verpoest. Lashwood and Bagshawe review genetic counseling, providing not only traditional ""how to"" checklists but also discussing the emotional impact experienced by client families. Defense mechanisms like denial and anger impede patients from gaining requisite knowledge, and must be overcome. Dondorp and de Wert extend this theme by their treatise on ethical considerations. Our authors have thus provided us with a text broad in coverage. Contributions by an international spectrum of authors - European and American - assure us provincial views are eschewed. Here we have a text that students, practitioners, and scientists involved in reproduction genetics should have on their shelves, or readily accessible in their computer."