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Background The potential of schistosomiasis to spread across borders, coupled with the considerable delay by which infected travellers and migrants are diagnosed in Europe, calls for better surveillance of the distribution of this disease. This study explored the geographical origin and genetic profiles of Schistosoma infections imported into Europe and diagnosed in a network of 11 European centres specialized in traveller and migrant health. Methods Genetic profiles were obtained from DNA extracted from concentrated Schistosoma eggs or Schistosoma -positive samples (faeces, urine, biopsy) collected during routine diagnostic procedures. The species-specific cytochrome oxidase sub-unit 1 ( cox1 ) diagnostic region and the standard complete internal transcribed spacer (ITS) 1 + ITS2 (ITS1 + 2) ribosomal DNA region were amplified and sequenced, together with a partial region of 18S ribosomal DNA in selected cases. Prevalences of the different genetic profiles within the whole patient cohort and by country/geographical area of possible infection were analysed. A phylogenetic analysis was performed using the larger cox1 (~ 956 base pairs) sequences dataset. Results A total of 94 samples were available for analysis, 36 from patients with a diagnosis of intestinal schistosomiasis and 58 with urinary schistosomiasis, all acquired in a sub-Saharan African country. Mitochondrial (mt) cox1 , nuclear ITS1 + 2 and/or 18S (mt/nuclear) genotypes were successfully obtained from 51/94 (54%) samples; while for 43/94 (46%) samples, only a partial mt genotype was obtained. Infections with Schistosoma haematobium and Schistosoma mansoni were identified in the majority of cases (66/94; 70%), while mixed Schistosoma spp. genetic profiles, which were identified in 30% (28/94) of the samples, were almost exclusively (27/28; 96%) associated with cases of urinary schistosomiasis. Among the urinary infections, almost half (27/58; 47%) could be identified as having a mixed genetic profile. These mostly (26/28; 93%) included genetic traits of S. haematobium and Schistosoma bovis , and all were from patients probably infected in West Africa. Conclusions Infections with S. haematobium and S. mansoni represent the majority of cases of schistosomiasis currently being diagnosed in Europe; however, mixed Schistosoma genetic profiles (mostly S. haematobium/S. bovis ) were identified in at least 30% of samples. Our results call for a coordinated effort encompassing prompt diagnosis and treatment of Schistosoma infections, together with monitoring of the possible introduction of species of Schistosoma and establishment of their autochthonous transmission under suitable conditions in Europe.

Backgrounds Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but lethal cardiac ion channelopathy. Delayed diagnosis and misdiagnosis remain a matter of concern due to its rarity and insufficient recognition of this disorder, particularly in developing countries like China. Aims and methods We reported six catecholaminergic polymorphic ventricular tachycardia (CPVT) children diagnosed in our center along with a comprehensive review of Chinese pediatric CPVT patients reported in domestic and overseas literature between January 2013 and December 2021 to provide an essential reference for physicians to deepen their understanding of pediatric CPVT. Results A total of 95 children with CPVT, including our six patients from 21 medical centers were identified. The median age of symptom onset is 8.7 ± 3.0 years. Diagnosis occurred at a median age of 12.9 ± 6.8 years with a delay of 4.3 ± 6.6 years. Selective beta-blockers (Metoprolol and Bisoprolol) were prescribed for 38 patients (56.7%) and 29 (43.3%) patients received non-selective beta-blocker (Propranolol and Nadolol) treatment. Six patients accepted LCSD and seven received ICD implantation at the subsequent therapy. A total of 13 patients died during the disease course. Of the 67 patients with positive gene test results, variants in RYR2 were 47 (70.1%), CASQ2 were 11 (16.4%), and RYR2 accompanied SCN5A were 7 (10.4%). Patients with CASQ2 gene mutations presented with younger symptom onset age, higher positive family history rate and better prognosis than those with RYR2 mutations. Conclusion Chinese pediatric patients with CPVT had a poorer prognosis than other cohorts, probably due to delayed/missed diagnosis, non-standard usage of beta-blockers, unavailability of flecainide, and a lower rate of LCSD and ICD implantation.

Heritability of antisocial behaviour is estimated at approximately 50% and involves multiple genes.AimsTo investigate the cumulative genetic effects of 116 single nucleotide polymorphisms mapping to 11 candidate serotonergic genes and antisocial behaviours, in adolescence and in early adulthood. Participants were 410 male members of the Quebec Longitudinal Study of Kindergarten Children, a population-based cohort followed up prospectively from age 6 to age 23. The serotonergic genes were selected based on known physiological processes and prior associations with antisocial behaviours. Antisocial behaviours were self-reported and assessed by using semi-structured interviews in adolescence and in adulthood. Cumulative, haplotype-based contributions of serotonergic genes conferring risk and protection for antisocial behaviours were detected by using multilocus genetic profile risk scores (MGPRSs) and multilocus genetic profile protection scores (MGPPSs). Cumulatively, haplotype-based MGPRSs and MGPPSs contributed to 9.6, 8.5 and 15.2% of the variance in general delinquency in adolescence, property/violent crimes in early adulthood and physical partner violence in early adulthood, respectively. This study extends previous research by showing a cumulative effect of multiple haplotypes conferring risk and protection to antisocial behaviours in adolescence and early adulthood. The findings further support the relevance of concomitantly considering multiple serotonergic polymorphisms to better understand the genetic aetiology of antisocial behaviours. Future studies should investigate the interplay between risk and protective haplotype-based multilocus genetic profile scores with the environment. I.O.-M. holds a Canada Research Chair in the developmental origins of vulnerability and resilience.

ObjectiveSporadic early-onset colorectal cancer (EOCRC) has bad prognosis, yet is poorly represented by cell line models. We examine the key mutational and transcriptomic alterations in an organoid biobank enriched in EOCRCs.DesignWe established paired cancer (n=32) and normal organoids (n=18) from 20 patients enriched in microsatellite-stable EOCRC. Exome and transcriptome analysis was performed.ResultsWe observed a striking diversity of molecular phenotypes, including PTPRK-RSPO3 fusions. Transcriptionally, RSPO fusion organoids resembled normal colon organoids and were distinct from APC mutant organoids, with high BMP2 and low PTK7 expression. Single cell transcriptome analysis confirmed the similarity between RSPO fusion organoids and normal organoids, with a propensity for maturation on Wnt withdrawal, whereas the APC mutant organoids were locked in progenitor stages. CRISPR/Cas9 engineered mutation of APC in normal human colon organoids led to upregulation of PTK7 protein and suppression of BMP2, but less so with an engineered RNF43 mutation. The frequent co-occurrence of RSPO fusions with SMAD4 or BMPR1A mutation was confirmed in TCGA database searches. RNF43 mutation was found in organoid from a leukaemia survivor with a novel mutational signature; and organoids with POLE proofreading mutation displayed ultramutation. The cancer organoid genomes were stable over long culture periods, while normal human colon organoids tended to be subject to clonal dominance over time.ConclusionsThese organoid models enriched in EOCRCs with linked genomic data fill a gap in existing CRC models and reveal distinct genetic profiles and novel pathway cooperativity.

Background Pacific salmon ( Oncorhynchus spp. ) serve as good biological indicators of the breadth of climate warming effects on fish because their anadromous life cycle exposes them to environmental challenges in both marine and freshwater environments. Our study sought to mine the extensive functional genomic studies in fishes to identify robust thermally-responsive biomarkers that could monitor molecular physiological signatures of chronic thermal stress in fish using non-lethal sampling of gill tissue. Results Candidate thermal stress biomarkers for gill tissue were identified using comparisons among microarray datasets produced in the Molecular Genetics Laboratory, Pacific Biological Station, Nanaimo, BC, six external, published microarray studies on chronic and acute temperature stress in salmon, and a comparison of significant genes across published studies in multiple fishes using deep literature mining. Eighty-two microarray features related to 39 unique gene IDs were selected as candidate chronic thermal stress biomarkers. Most of these genes were identified both in the meta-analysis of salmon microarray data and in the literature mining for thermal stress markers in salmonids and other fishes. Quantitative reverse transcription PCR (qRT-PCR) assays for 32 unique genes with good efficiencies across salmon species were developed, and their activity in response to thermally challenged sockeye salmon ( O. nerka ) and Chinook salmon ( O. tshawytscha ) (cool, 13–14 °C and warm temperatures 18–19 °C) over 5–7 days was assessed. Eight genes, including two transcripts of each SERPINH1 and HSP90AA1, FKBP10, MAP3K14, SFRS2, and EEF2 showed strong and robust chronic temperature stress response consistently in the discovery analysis and both sockeye and Chinook salmon validation studies. Conclusions The results of both discovery analysis and gene expression showed that a panel of genes involved in chaperoning and protein rescue, oxidative stress, and protein biosynthesis were differentially activated in gill tissue of Pacific salmon in response to elevated temperatures. While individually, some of these biomarkers may also respond to other stressors or biological processes, when expressed in concert, we argue that a biomarker panel comprised of some or all of these genes could provide a reliable means to specifically detect thermal stress in field-caught salmon.

Among nearly 2400 men with prostate cancer, next-generation sequencing of 474 genes showed differences among racial groups in the frequency of mutations in certain genes. Such variations could affect both prognosis and response to therapy in these patients.

Objective To identify the genetic characteristics in a large-scale of patients with Charcot-Marie-Tooth disease (CMT).MethodsFrom May 2012 to August 2016, we collected 1005 cases with suspected CMT throughout Japan, whereas PMP22 duplication/deletion were excluded in advance for demyelinating CMT cases. We performed next-generation sequencing targeting CMT-related gene panels using Illumina MiSeq or Ion Proton, then analysed the gene-specific onset age of the identified cases and geographical differences in terms of their genetic spectrum.Results From 40 genes, we identified pathogenic or likely pathogenic variants in 301 cases (30.0%). The most common causative genes were GJB1 (n=66, 21.9%), MFN2 (n=66, 21.9%) and MPZ (n=51, 16.9%). In demyelinating CMT, variants were detected in 45.7% cases, and the most common reasons were GJB1 (40.3%), MPZ (27.1%), PMP22 point mutations (6.2%) and NEFL (4.7%). Axonal CMT yielded a relatively lower detection rate (22.9%), and the leading causes, occupying 72.4%, were MFN2 (37.2%), MPZ (9.0%), HSPB1 (8.3%), GJB1 (7.7%), GDAP1 (5.1%) and MME (5.1%). First decade of life was found as the most common disease onset period, and early-onset CMT cases were most likely to receive a molecular diagnosis. Geographical distribution analysis indicated distinctive genetic spectrums in different regions of Japan.Conclusions Our results updated the genetic profile within a large-scale of Japanese CMT cases. Subsequent analyses regarding onset age and geographical distribution advanced our understanding of CMT, which would be beneficial for clinicians.

Background Recent ancient DNA studies uncovering large-scale demographic events in Iberia have presented very limited data for Portugal, a country located at the westernmost edge of continental Eurasia. Here, we present the most comprehensive collection of Portuguese ancient genome-wide data, from 67 individuals spanning 5000 years of human history, from the Neolithic to the nineteenth century. Results We identify early admixture between local hunter-gatherers and Anatolian-related farmers in Neolithic Portugal, with a northeastern–southwestern gradient of increasing Magdalenian-associated ancestry persistence in Iberia. This profile continues into the Chalcolithic, though Bell Beaker-associated sites reveal Portugal’s first evidence of Steppe-related ancestry. Such ancestry has a broader demographic impact during the Bronze Age, despite continuity of local Chalcolithic genetic ancestry and limited Mediterranean connections. The village of Idanha-a-Velha emerges in the Roman period as a site of significant migration and interaction, presenting a notably diverse genetic profile that includes North African and Eastern Mediterranean ancestries. The Early Medieval period is marked by the arrival of Central European genetic diversity, likely linked to migrations of Germanic tribes, adding to coeval local, African, and Mediterranean influences. The Islamic and Christian Conquest periods show strong genetic continuity in northern Portugal and significant additional African admixture in the south. The latter remains stable during the post-Islamic period, suggesting enduring African influences. Conclusions We reveal dynamic patterns of migration in line with cultural exchange across millennia, but also the persistence of local ancestries. Our findings integrate genetic information with historical and archeological data, enhancing our understanding of Iberia’s biological and cultural heritage.

Background Primary cardiomyopathies are major causes of heart failure, placing a substantial burden on both individuals and society. Revealing its genetic profiles can lead to a better understanding of the mechanism and is critical for disease prevention and treatment. Method Primary cardiomyopathy patients were enrolled and whole exome sequence was conducted to analyze their genetic profiles. Retrospective clinical information extraction and analysis of sequence data were implemented. Results A total of 77 primary cardiomyopathy patients were enrolled, comprising 65 patients with dilated cardiomyopathy (DCM) and 12 with hypertrophic cardiomyopathy (HCM). Among the DCM patients, 13 variants classified as pathogenic (P) or likely pathogenic (LP) were identified in 12 patients (18.46%), predominantly in genes associated with the nuclear envelope and sarcomere. Among HCM patients, 6 P/LP variants were discovered in 6 (50%) patients. Taking variants of uncertain significance (VUS) into consideration, an analysis of the association between the number of variants carried by patients and their clinical characteristics revealed that DCM patients with more than one variant had a higher proportion of hyperuricemia. Conclusions We map a comprehensive profile of primary cardiomyopathy in Chinese population and, for the first time, identify a possible association between hyperuricemia and the number of genetic variants carried by DCM patients.

Do genetic risk profiles for drug use disorder (DUD), major depression (MD), and attention-deficit hyperactivity disorder (ADHD) differ substantially as a function of sex, age at onset (AAO), recurrence, mode of ascertainment, and treatment? Family genetic risk scores (FGRS) for MD, anxiety disorders, bipolar disorder, schizophrenia, alcohol use disorder, DUD, ADHD, and autism-spectrum disorder were calculated from 1st-5th degree relatives in the Swedish population born 1932-1995 ( = 5 829 952). Profiles of these FGRS were obtained and compared across various subgroups of DUD, MD, and ADHD cases. Differences in FGRS profiles for DUD, MD, and ADHD by sex were modest, but they varied substantially by AAO, recurrence, ascertainment, and treatment with scores typically higher in cases with greater severity (e.g. early AAO, high recurrence, ascertainment in high intensity clinical settings, and treatment). However, severity was not always related to purer genetic profiles, as genetic risk for many disorders often increased together. However, some results, such as by mode of ascertainment from different Swedish registries, produced qualitative differences in FGRS profiles. Differences in FGRS profiles for DUD, MD, and ADHD varied substantially by AAO, recurrence, ascertainment, and treatment. Replication of psychiatric studies, particularly those examining genetic factors, may be difficult unless cases are matched not only by diagnosis but by important clinical characteristics. Genetic correlations between psychiatric disorders could arise through one disorder impacting on the patterns of ascertainment for the other, rather than from the direct effects of shared genetic liabilities.