BACKGROUND: Somatic and germline genetic alterations are significant drivers of cancer. Increasing integration of new technologies which profile these alterations requires timely, equitable and high-quality genetic counselling to facilitate accurate diagnoses and informed decision-making by patients and their families in preventive and clinical settings. This article aims to provide an overview of genetic counselling legislation and practice across European Union (EU) Member States to serve as a foundation for future European recommendations and action. METHODS: National legislative databases of all 27 Member States were searched using terms relevant to genetic counselling, translated as appropriate. Interviews with relevant experts from each Member State were conducted to validate legislative search results and provide detailed insights into genetic counselling practice in each country. RESULTS: Genetic counselling is included in national legislative documents of 22 of 27 Member States, with substantial variation in legal mechanisms and prescribed details (i.e. the 'who, what, when and where' of counselling). Practice is similarly varied. Workforce capacity (25 of 27 Member States) and genetic literacy (all Member States) were common reported barriers. Recognition and/or better integration of genetic counsellors and updated legislation and were most commonly noted as the 'most important change' which would improve practice. CONCLUSIONS: This review highlights substantial variability in genetic counselling across EU Member States, as well as common barriers notwithstanding this variation. Future recommendations and action should focus on addressing literacy and capacity challenges through legislative, regulatory and/or strategic approaches at EU, national, regional and/or local levels.

• MeSH
• Evropská unie * MeSH
• genetické poradenství * zákonodárství a právo   MeSH
• genetické testování zákonodárství a právo   MeSH
• lidé MeSH
• nádory * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Modern humans have populated Europe for more than 45,000 years1,2. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period3. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago. We identify a genetic ancestry profile in individuals associated with Upper Palaeolithic Gravettian assemblages from western Europe that is distinct from contemporaneous groups related to this archaeological culture in central and southern Europe4, but resembles that of preceding individuals associated with the Aurignacian culture. This ancestry profile survived during the Last Glacial Maximum (25,000 to 19,000 years ago) in human populations from southwestern Europe associated with the Solutrean culture, and with the following Magdalenian culture that re-expanded northeastward after the Last Glacial Maximum. Conversely, we reveal a genetic turnover in southern Europe suggesting a local replacement of human groups around the time of the Last Glacial Maximum, accompanied by a north-to-south dispersal of populations associated with the Epigravettian culture. From at least 14,000 years ago, an ancestry related to this culture spread from the south across the rest of Europe, largely replacing the Magdalenian-associated gene pool. After a period of limited admixture that spanned the beginning of the Mesolithic, we find genetic interactions between western and eastern European hunter-gatherers, who were also characterized by marked differences in phenotypically relevant variants.

• MeSH
• archeologie * MeSH
• dějiny starověku MeSH
• genetika člověka * MeSH
• genom lidský * genetika   MeSH
• genomika * MeSH
• genový pool MeSH
• lidé MeSH
• lov * MeSH
• paleontologie * MeSH
• Check Tag
• dějiny starověku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa etnologie   MeSH

If genome sequencing is performed in health care, in theory the opportunity arises to take a further look at the data: opportunistic genomic screening (OGS). The European Society of Human Genetics (ESHG) in 2013 recommended that genome analysis should be restricted to the original health problem at least for the time being. Other organizations have argued that 'actionable' genetic variants should or could be reported (including American College of Medical Genetics and Genomics, French Society of Predictive and Personalized Medicine, Genomics England). They argue that the opportunity should be used to routinely and systematically look for secondary findings-so-called opportunistic screening. From a normative perspective, the distinguishing characteristic of screening is not so much its context (whether public health or health care), but the lack of an indication for having this specific test or investigation in those to whom screening is offered. Screening entails a more precarious benefits-to-risks balance. The ESHG continues to recommend a cautious approach to opportunistic screening. Proportionality and autonomy must be guaranteed, and in collectively funded health-care systems the potential benefits must be balanced against health care expenditures. With regard to genome sequencing in pediatrics, ESHG argues that it is premature to look for later-onset conditions in children. Counseling should be offered and informed consent is and should be a central ethical norm. Depending on developing evidence on penetrance, actionability, and available resources, OGS pilots may be justified to generate data for a future, informed, comparative analysis of OGS and its main alternatives, such as cascade testing.

• MeSH
• genetické testování etika   normy   MeSH
• genetika člověka etika   organizace a řízení   normy   MeSH
• lidé MeSH
• směrnice pro lékařskou praxi jako téma * MeSH
• společnosti lékařské normy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

AIMS: This is a nation-wide survey of chronic lymphocytic leukemia (CLL) patients at six large hematology centers in the Czech Republic. The aim was to identify specific populations, social, and health characteristics of CLL subgroups divided according to the immunogenetic features of their B cell receptors (BCRs) and clonality. PATIENTS AND METHODS: Questionnaires directed to specific health, social, and environmental conditions were collected in a cohort of 573 CLL patients. For these patients, immunoglobulin heavy chain gene rearrangements were also analyzed in order to gain information about their clonality, IGHV mutational status, and the presence of stereotyped BCRs. Data extracted from the questionnaires were analyzed statistically in the context of immunogenetic features of the cohort. RESULTS: There were no statistically significant differences in the data collected in the survey between patients with mutated and patients with unmutated IGHV. However, patients with oligoclonal CLL reported health conditions such as hypercholesterolemia, hypertension, herpes simplex, tumors, and also, separately, CLL in 1st degree relatives, more often than their monoclonal counterparts. In patients with stereotyped BCRs, we found more frequent alcohol consumption and gastric infections in subset #1 cases and frequent cholecystectomies and familial CLL in subset #2 cases. CONCLUSION: To the best of our knowledge, this study is the first to investigate CLL immunogenetic features and clonality in the context of epidemiological data. We reported statistically significant associations suggesting the influence of certain health and social conditions on a number of clonal populations expanding in CLL and also on characteristic BCR features, especially stereotypy.

• Klíčová slova
• B-cell receptor, biological risk factor, chronic lymphocytic leukemia, clonality, patient history, questionnaire,
• MeSH
• biologické faktory * MeSH
• chronická lymfatická leukemie epidemiologie   genetika   imunologie   MeSH
• dospělí MeSH
• genetická variace * MeSH
• genetika člověka MeSH
• genotyp MeSH
• imunogenetika * MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• receptory antigenů B-buněk genetika   MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• biologické faktory * MeSH
• receptory antigenů B-buněk MeSH

BACKGROUND: Alopecia areata (AA) is mainly a T cell-medicated autoimmune disease with non-scarring hair loss and limited treatment options. Of these, the patchy-type alopecia areata (AAP) is the most common and relatively easy to treat due to smaller areas of the scalp affected. To understand the pathogenesis of AAP and explore the therapeutic target, we focus on the molecular signatures by comparing AAP and normal subjects. METHODS: The gene expression profile (GSE68801) was obtained from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified between AAP patients and normal controls using the GEO2R. Then the Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Protein-Protein interaction (PPI) network analysis were performed for DEGs. RESULTS: A total of 185 DEGs were identified, including 45 up-regulated genes and 140 down-regulated genes. The up-regulated DEGs were related to the immune response and chemokine signaling pathway. Meanwhile, down-regulated DEGs were enriched in keratin filament and intermediate filament. Subsequently, the top 10 hub genes were picked out in the PPI network, among them, CD2 showed the highest connectivity degree and central roles. CONCLUSION: Our data suggest that the CD2 may be a new therapeutic target for AAP. Further study is needed to explore the value of CD2 in the treatment of alopecia areata.

• Klíčová slova
• CD2., differentially expressed genes, function enrichment, patchy-type alopecia areata, protein‑protein interaction network,
• MeSH
• alopecia areata genetika   terapie   MeSH
• antigeny CD2 genetika   MeSH
• genetická terapie metody   MeSH
• genetika člověka MeSH
• lidé MeSH
• stanovení celkové genové exprese metody   MeSH
• výpočetní biologie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• antigeny CD2 MeSH

BACKGROUND: Genetic testing rapidly penetrates into all medical specialties and medical students must acquire skills in this area. However, many of them consider it difficult. Furthermore, many find these topics less appealing and not connected to their future specialization in different fields of clinical medicine. Student-centred strategies such as problem-based learning, gamification and the use of real data can increase the appeal of a difficult topic such as genetic testing, a field at the crossroads of genetics, molecular biology and bioinformatics. METHODS: We designed an electronic teaching application which students registered in the undergraduate Medical Biology course can access online. A study was carried out to assess the influence of implementation of the new method. We performed pretest/posttest evaluation and analyzed the results using the sign test with median values. We also collected students' personal comments. RESULTS: The newly developed interactive application simulates the process of molecular genetic diagnostics of a hereditary disorder in a family. Thirteen tasks guide students through clinical and laboratory steps needed to reach the final diagnosis. Genetics and genomics are fields strongly dependent on electronic databases and computer-based data analysis tools. The tasks employ publicly available internet bioinformatic resources used routinely in medical genetics departments worldwide. Authenticity is assured by the use of modified and de-identified clinical and laboratory data from real families analyzed in our previous research projects. Each task contains links to databases and data processing tools needed to solve the task, and an answer box. If the entered answer is correct, the system allows the user to proceed to the next task. The solving of consecutive tasks arranged into a single narrative resembles a computer game, making the concept appealing. There was a statistically significant improvement of knowledge and skills after the practical class, and most comments on the application were positive. A demo version is available at https://medbio.lf2.cuni.cz/demo_m/ . Full version is available on request from the authors. CONCLUSIONS: Our concept proved to be appealing to the students and effective in teaching medical molecular genetics. It can be modified for training in the use of electronic information resources in other medical specialties.

• Klíčová slova
• Bioinformatics, E-learning, Gamification, Genomics, Interactive teaching application, Medical databases, Medical genetics, Problem-based learning,
• MeSH
• genetické nemoci vrozené diagnóza   MeSH
• genetické testování * MeSH
• lékařská genetika výchova   MeSH
• lidé MeSH
• molekulární medicína výchova   MeSH
• počítačem řízená výuka * MeSH
• problémově orientovaná výuka MeSH
• studium lékařství pregraduální metody   MeSH
• uživatelské rozhraní počítače MeSH
• videohry MeSH
• výpočetní biologie výchova   MeSH
• vyučování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH

Rapid development of clinical genetics was enabled by the advances of molecular genetic laboratory diagnostics. Genetic laboratory testing has unique characteristics, and results of germinal genome testing has consequences not only for the patient but also for his relatives. Genetic laboratory testing in the Czech Republic is governed by the act no. 373/2011, which explicitly states that the testing requires the completion of a written informed consent. This article explains in detail the process of obtaining an informed consent within a broader framework of genetic counselling. An informed consent with genetic laboratory testing not only informs the patient (this being its primary purpose), but can also serve as a lead for physicians of other clinical specialties intending to order genetic laboratory tests.

• Klíčová slova
• clinical genetics, genetic counselling, genetic laboratory testing, informed consent,
• MeSH
• genetické poradenství * MeSH
• genetické testování * MeSH
• informovaný souhlas pacienta * MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

About 5-10 % of cancer diseases may be caused by genetic predisposition, in ovarian cancer it could be almost 20 % of cases. The cause is mostly a pathogenic germline mutation in tumor suppressor genes, DNA repair genes, less frequently in oncogenes. So far, we know more than 200 hereditary cancer syndromes. The most frequently tested are hereditary breast and ovarian cancer syndrome, hereditary nonpolyposis colorectal cancer (Lynch syndrome), quite frequent are also hereditary gastrointestinal polyposes. Genetic counseling and testing are routinely available for patients or their relatives. Testing methods are changing; nowadays we use next generation sequencing methods (massive parallel sequencing) with testing of panels of high-risk genes. If the mutation is discovered, we may offer the testing to relatives. Genetic testing is indicated by medical geneticist after the genetic counseling session. High-risk individuals should be followed oncology clinics or by other specialists.

• Klíčová slova
• genetic counseling, genetic testing, hereditary cancer syndromes,
• MeSH
• dědičné nádorové syndromy * diagnóza   genetika   prevence a kontrola   MeSH
• dědičné nepolypózní kolorektální nádory * diagnóza   genetika   prevence a kontrola   MeSH
• genetická predispozice k nemoci MeSH
• genetické poradenství MeSH
• genetické testování MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Although awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Despite FH being a genetic disorder, genetic testing is rarely used. The Familial Hypercholesterolemia Foundation convened an international expert panel to assess the utility of FH genetic testing. The rationale includes the following: 1) facilitation of definitive diagnosis; 2) pathogenic variants indicate higher cardiovascular risk, which indicates the potential need for more aggressive lipid lowering; 3) increase in initiation of and adherence to therapy; and 4) cascade testing of at-risk relatives. The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives. Testing should include the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes include greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk stratification.

• Klíčová slova
• cascade testing, consensus statement, familial hypercholesterolemia, genetic counseling, genetic testing,
• MeSH
• apolipoproteiny B krev   genetika   MeSH
• genetické poradenství metody   normy   MeSH
• genetické testování metody   normy   MeSH
• hyperlipoproteinemie typ II krev   diagnóza   genetika   MeSH
• lidé MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 krev   genetika   MeSH
• receptory LDL krev   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• apolipoproteiny B MeSH
• LDLR protein, human MeSH Prohlížeč
• PCSK9 protein, human MeSH Prohlížeč
• proproteinkonvertasa subtilisin/kexin typu 9 MeSH
• receptory LDL MeSH

The prenatal finding of a small supernumerary marker chromosome (sSMC) is a challenge for genetic counseling. Our analytic algorithm is based on sSMC frequencies and multicolor FISH to accelerate the procedure. The chromosomal origin, size, and degree of mosaicism of the sSMC then determine the prognosis. We illustrate the effectiveness on 4 prenatally identified de novo mosaic sSMCs derived from chromosomes 13/21, X, 3, and 17. Three sSMC carriers had a good prognosis and apparently healthy children were born, showing no abnormality till the last examination at the age of 4 years. One case had a poor prognosis, and the parents decided to terminate the pregnancy. Our work contributes to the laboratory and clinical management of prenatally detected sSMCs. FISH is a reliable method for fast sSMC evaluation and prognosis assessment; it prevents unnecessary delays and uncertainty, allows informed decision making, and reduces unnecessary pregnancy terminations.

• Klíčová slova
• FISH, Genetic prognosis, Marker chromosome, Mosaicism, Prenatal diagnosis, Reproductive decision-making, Small supernumerary marker chromosome,
• MeSH
• algoritmy MeSH
• chromozomální aberace * MeSH
• dospělí MeSH
• genetické asociační studie MeSH
• genetické poradenství MeSH
• heterozygot * MeSH
• hybridizace in situ fluorescenční MeSH
• karyotypizace MeSH
• kojenec MeSH
• lidé MeSH
• předškolní dítě MeSH
• prenatální diagnóza * MeSH
• prognóza MeSH
• těhotenství MeSH
• věk matky MeSH
• Check Tag
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH