Titel Deelnemers "Korte inhoud" "Dactylogyridae 2022: a meta-analysis of phylogenetic studies and generic diagnoses of parasitic flatworms using published genetic and morphological data" "Antoine Pariselle, Karen SMEETS, Tom ARTOIS, Maarten VANHOVE" "Dactylogyridae is one of the most studied families of parasitic flatworms with more than 1000 species and 166 genera described to date including ecto- and endoparasites. Dactylogyrid monogeneans were suggested as model organisms for host-parasite macroevolutionary and biogeographical studies due to the scientific and economic importance of some of their host lineages. Consequently, an array of phylogenetic research into different dactylogyrid lineages has been produced over the past years but the last family-wide study was published 16 years ago. Here, we provide a meta-analysis of the phylogenetic relationships of Dactylogyridae including representatives of all genera with available molecular data (n = 67). First, we investigate the systematic informativeness of morphological characters widely used to diagnose dactylogyrid genera through a parsimony analysis of the characters, character mapping, and phylogenetic comparative methods. Second, we provide an overview of the current state of the systematics of the family and its subfamilies, and summarise potentially poly- and paraphyletic genera. Third, we elaborate on the implications of taxonomic, citation, and confirmation bias in past studies. Fourth, we discuss host range, biogeographical, and freshwater-marine patterns. We found two well-supported macroclades which we assigned to the subfamilies Dactylogyrinae and Ancyrocephalinae. These subfamilies further include 16 well-supported clades with only a few synapomorphies that could be deduced from generic diagnoses in the literature. Furthermore, few morphological characters considered systematically informative at the genus level display a strong phylogenetic signal. However, the parsimony analysis suggests that these characters provide little information on the relationships between genera. We conclude that a strong taxonomic bias and low coverage of DNA sequences and regions limit knowledge on morphological and biogeographical evolutionary patterns that can be inferred from these results. We propose addressing potential citation and confirmation biases through a 'level playing field' multiple sequence alignment as provided by this study." "[Genetic counselling and testing in pulmonary arterial hypertension - A consensus statement on behalf of the International Consortium for Genetic Studies in PAH - French version]." "Catharina Belge, Rozenn Quarck" "Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, BMPR2 (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives through the process of genetic counselling, and describe the presently known disease causal genes to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH include the identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials, and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered." "Genetics of FTLD: overview and what else we can expect from genetic studies" "Cyril Pottier, Thomas A. Ravenscroft, Monica Sanchez-Contreras, Rosa Rademakers" "Frontotemporal lobar degeneration (FTLD) comprises a highly heterogeneous group of disorders clinically associated with behavioral and personality changes, language impairment, and deficits in executive functioning, and pathologically associated with degeneration of frontal and temporal lobes. Some patients present with motor symptoms including amyotrophic lateral sclerosis. Genetic research over the past two decades in FTLD families led to the identification of three common FTLD genes (microtubule-associated protein tau, progranulin, and chromosome 9 open reading frame 72) and a small number of rare FTLD genes, explaining the disease in almost all autosomal dominant FTLD families but only a minority of apparently sporadic patients or patients in whom the family history is less clear. Identification of additional FTLD (risk) genes is therefore highly anticipated, especially with the emerging use of next-generation sequencing. Common variants in the transmembrane protein 106 B were identified as a genetic risk factor of FTLD and disease modifier in patients with known mutations. This review summarizes for each FTLD gene what we know about the type and frequency of mutations, their associated clinical and pathological features, and potential disease mechanisms. We also provide an overview of emerging disease pathways encompassing multiple FTLD genes. We further discuss how FTLD specific issues, such as disease heterogeneity, the presence of an unclear family history and the possible role of an oligogenic basis of FTLD, can pose challenges for future FTLD gene identification and risk assessment of specific variants. Finally, we highlight emerging clinical, genetic, and translational research opportunities that lie ahead." "Population genetic studies on zooplankton: patterns of genetic variation in organisms inhabiting insular habitats as a means of comparing the merits of different nature conservation strategies" "L De Meester, E Michels, J Vanoverbeke, C Cousyn, H Degans, E Audenaert, K Desender, Jean-Pierre Maelfait" "Zooplankton organisms are rarely the target of nature conservation efforts, probably because they are small and not well known to the public. Yet, information on zooplankton organisms may be very useful for nature conservation. First, some rare species have very specific habitat requirements. Secondly, the species composition and size distribution of the zooplankton community may reveal a wealth of information on habitat characteristics, including on biotic factors such as fish predation pressure which is often difficult to assess directly. In addition, zooplankton organisms play a key role in the trophic cascade, and knowledge on their ecology is therefore essential to the restoration of water quality in lakes through biomanipulation (CARPENTER & KITCHELL 1993). Another important factor is that many zooplankton species, and especially members of the genus Daphnia, are well-suited for population genetic studies, because they typically occur in large numbers and have a short generation time. In addition, quantitative genetic studies are encouraged because several Daphnia species are relatively easy to rear in the laboratory and one can work with clones (DE MEESTER 1996b). Moreover, as zooplankton typically inhabits insular habitats such as ponds and lakes, studies on the genetic variation in these organisms may reveal patterns that are of general relevance for nature conservation strategies related to the design of nature reserves (which are often islands in a cultural landscape) and the consequences of habitat fragmentation (which is a process of insulating populations) (see SHAFER 1990, LOESCHCKE et al. 1994, SPELLERBERG 1996). We have started a survey study on the genetic diversity within and the genetic differentiation among populations of several cladoceran taxa, including several Daphnia species (D. magna, D. pulex and the introduced species D. ambigua) and some in our region less common species (Sida crystallina, Polyphemus pediculus and Megafenestra aurita). From each (sub)population studied, 40-60 individuals are analyzed for genetic variation at four to nine polymorphic loci by cellulose acetate electrophoresis. As all taxa studied are cyclical parthenogenetic, the genetic diversity of populations can be assessed by calculating clonal diversity. Our preliminary results on D. magna, Sida crystalline and Megafenestra aurita suggest that ( 1) there is a weak but significant relationship between habitat area and clonal diversity. For both the littoral species Sida and Megafenestra, the relationship is better when the surface area of the littoral zone rather than the surface area of the whole water body is taken into consideration. (2) There is a strong inverse relationship between genetic differentiation among populations and the average clonal diversity (VANOVERBEKE & DE MEESTER in press). This relationship reflects a drift phenomenon, and blurs the relationship between genetic and geographic distance. (3) Quantitative genetic data on phototactic behaviour illustrate that Daphnia magna populations can show a pronounced local adaptation (DE MEESTER 1996a). These data suggest that one should be prudent in linking different isolated habitats in an effort to create larger habitats, because this may lead to outbreeding depression and a loss of genetic diversity on a regional scale. We are currently studying genetic diversity in a Daphnia metapopulation to assess the effect of corridors among habitats with respect to local and regional genetic diversity. In addition, we study the erosion of genetic diversity during the course of the growing season of moderately large Daphnia populations to learn how clonal selection and drift phenomena lead to the observed relationship between clonal diversity and habitat size." "Genetic counselling and testing in pulmonary arterial hypertension: a consensus statement on behalf of the International Consortium for Genetic Studies in PAH" "Catharina Belge, Rozenn Quarck" "Pulmonary arterial hypertension (PAH) is a rare disease that can be caused by (likely) pathogenic germline genomic variants. In addition to the most prevalent disease gene, BMPR2 (bone morphogenetic protein receptor 2), several genes, some belonging to distinct functional classes, are also now known to predispose to the development of PAH. As a consequence, specialist and non-specialist clinicians and healthcare professionals are increasingly faced with a range of questions regarding the need for, approaches to and benefits/risks of genetic testing for PAH patients and/or related family members. We provide a consensus-based approach to recommendations for genetic counselling and assessment of current best practice for disease gene testing. We provide a framework and the type of information to be provided to patients and relatives through the process of genetic counselling, and describe the presently known disease causal genes to be analysed. Benefits of including molecular genetic testing within the management protocol of patients with PAH include the identification of individuals misclassified by other diagnostic approaches, the optimisation of phenotypic characterisation for aggregation of outcome data, including in clinical trials, and importantly through cascade screening, the detection of healthy causal variant carriers, to whom regular assessment should be offered." "Genetic multilocus studies of different strains of Cryptococcus neoformans: taxonomy and genetic structure" "S Bertout, F Renaud, Danielle Swinne, M Mallié, JM Bastide" "Genetic association studies of fibromuscular dysplasia identify new risk LOCI and shared genetic basis with more common vascular diseases" "Adrien Georges, Min-Lee Yang, Takiy-Eddine Berrandou, Mark Bakker, Ozan Dikilitas, Lijiang Ma, Benjamin A. Satterfield, Sebanti Sengupta, Kristina L. Hunker, Laurence Amar, Aurelien Lorthioir, Aleksander Prejbisz, Marco Pappaccogli, Ynte Ruigrok, Jeffrey W. Olin, Heather L. Gornik, Ernst Rietzschel, Ewa Warchol Celinska, Andrzej Januszewicz, Iftikhar J. Kullo, Michel Azizi, Xavier Jeunemaitre, Alexandre Persu, Jason C. Kovacic, Santhi K. Ganesh, Nabila Bouatia-Naji" "GENESTAT : an information portal for design and analysis of genetic association studies" "Samuli Ripatti, Tim Becker, Heike Bickeboller, Annica Dominicus, Christine Fischer, Keith Humphreys, Gudrun Jonasdottir, Yves Moreau, Marita Olsson, Alexander Ploner, Nuala Sheehan, Kristel Van Steen, Max Baur, Cornelia van Duijn, Juni Palmgren" "We present the rationale, the background and the structure for version 2.0 of the GENESTAT information portal (www.genestat.org) for statistical genetics. The fast methodological advances, coupled with a range of standalone software, makes it difficult for expert as well as non-expert users to orientate when designing and analysing their genetic studies. The ultimate ambition of GENESTAT is to guide on statistical methodology related to the broad spectrum of research in genetic epidemiology. GENESTAT 2.0 focuses on genetic association studies. Each entry provides a summary of a topic and gives links to key papers, websites and software. The flexibility of the internet is utilised for cross-referencing and for open editing. This paper gives an overview of GENESTAT and gives short introductions to the current main topics in GENESTAT, with additional entries on the website. Methods and software developers are invited to contribute to the portal, which is powered by a Wikipedia-type engine and allows easy additions and editing." "Testing different approaches to construct an olive (Olea europaea L.) core subset suitable for association genetic studies" "Ahmed El Bakkali, H Haouane, Patrick Van Damme, Bouchaib Khadari" "Evaluation of genetic diversity is of great interest for the management of germplasm collections and breeding programs. Management can be efficient when the evaluation is focused on a subset of accessions that represents the variability observed in the whole germplasm collection. Most core sets have been developed for seed crops using different approaches and sampling size to select entries on the basis of genetic and/or phenotypic data, while few studies on perennial crops have been published. Here, we proposed a core collection for cultivated olive (Olea europaea L.) using both Simple Sequence Repeat (SSR) markers and phenotypic traits by testing different sampling approaches including stratified and non-stratified methods. Twelve SSR markers were used to construct a core subset from an initial collection of 505 single genotypes sourced from 14 Mediterranean countries. Among all the sampling methods, we showed that a sample size of 12.5% was most suitable in capturing all the observed alleles using the M-method approach. Based on both SSR and phenotypic data, we established an initial core set, including the main Mediterranean cultivars, which displayed the highest genetic and phenotypic variability. No obvious genetic structure was indicated when the core subset was analyzed with Principal Coordinate analysis (PCoA). Our results gave an efficient basis as a first step for olive association mapping. The constructed core subset could be further evaluated for traits of agronomic interest, leading to association between the allelic variation and the phenotypic variability." "Expanding GNAS-related pathology by genetic and epigenetic studies" "Benedetta Izzi" "TheGNAS cluster, located on chromosome20q13 gives rise to several transcripts, antisensetranscripts andnoncoding RNAs, including transcription of the gene for the stimulatory G-proteinalpha subunit (Gsα), which interacts with adenylyl cyclase to generate cAMP. It comprisesfour alternative first exons and promoters that splice onto exon 2 of theclassical GNAS gene, and that are alllocated in three differentially methylated regions (DMRs) namelyNESP, XL and ExonA/B. The phenotypes resulting from genetic and epigenetic abnormalitiesof the GNAS region include AlbrightHereditary Osteodystrophy (AHO), pseudohypoparathyroidism types Ia (PHP-Ia) andIb (PHP-Ib), and pseudopseudohypoparathyroidism (PPHP). PHP-Ia and PPHP arecaused by inactivating GNASmutations, while PHP-Ib results from epigenetic GNAS mutations. All different aspects of epigenetics and with afocus on DNA methylation and the imprinted GNAScluster are reviewed in chapters 1and 3.Our research groupdeveloped a reproducible and reliable platelet-based functional Gs test, termedplatelet aggregation-inhibition test which is based uponinhibition of platelet aggregation by cAMP after Gs stimulation. Via this test270 patients with AHO features were screened and further classified in Gs hypo-(24%), hyper- (15%) or normal function. My PhD project will mainly focus on the finding of new(epi)genetic causes associated with an AHO phenotype and/or having PTHresistance in combination with a defective platelet Gs signaling pathway. In chapters 5 and 6, we have described theset up and validation of methodologies to study methylation in the different GNAS DMRs. Chapter 5 reports an easy screening method to detect pronounced GNAS methylation abnormalities such as forPHP-Ib patients. Chapters 6 fully describe the optimization and validationof a quantitative methodology (Sequenom EpiTYPER mass-array) that allows thesimultaneously study of different CpGs on large samples sets. The technique wasvalidated in PHP-Ib and PHP-Ia cases to quantify their GNAS methylation defect. Chapter7 reports the first study of GNASCopy Number Variants (CNVs) that showedno evidence for CNVs in AHO patientswith or without abnormal Gs platelet function. PPHP patients with Gshypofunction but no GNAS codingmutation were investigated for imprinting defects in chapter 8. Since AHO features are shared characteristics also withother imprinting dysorders, we have also studied other imprinting genes such asIGF2/H19, SNURF and GRB10. We found that PPHP patients have XL and IGF2hypermethylation in combination with SNURF hypomethylation. SinceGs hypofunction was also found in platelets from 5 spina bifida patients withAlbrights Hereditary Osteodystrophy carrying a peculiar GNAS splice mutation, 96 other spina bifida cases were included forfurther (epi‐)genetic GNAS studies (chapter 9). Identification of abnormalExonA/B methylation in 20% of 77 patients was the basis for further methylationstudies in SB patients. Evidence exists for a possible role for methylation inthe aetiology of NTDs (chapter 2 forreview on NTDs). We have studied for the first time DNA methylation in SB casesat genomic-scale level using the human 27K BeadChip array from Illumina thatincludes more than 27.000 CpGs. CpGs in ZNF718,KCNQ1, GSTT1, TP53INP1, MRI1 and ACOT11 were significantly hypermethylated, while the FL45964 CpGs werehypomethylated in SB patients. The genome-wide findings were replicated withthe Sequenom EpiTYPER and confirmed on a total of 101 SB patients for ACOT11, GSTT1 and ZNF718. The zebrafish ortholog ACOT11a gene was depleted in zebrafish embryos and life-screeningexperiments revealed a phenotype of neurulation defects but this deservesfurther characterization. Further studies on larger patients sets are needed tobetter characterize these preliminary findings. In conclusion, we have expanded human GNAS-related pathology by both geneticand epigenetic studies revealing a potential relevant role of this gene in theaetiology of different pathological phenotypes, once again highlighting theextreme complexity of this fascinating, and still not completely known,imprinted gene cluster."