scholarly journals Prevalence and polymorphism of a mussel transmissible cancer in Europe

2021 ◽  
Author(s):  
Maurine Hammel ◽  
Alexis Simon ◽  
Christine Arbiol ◽  
Antonio Villalba ◽  
Erika A.V. Burioli ◽  
...  
Keyword(s):  
Point Mutations ◽  
Geographic Area ◽  
Malignant Cell ◽  
Null Alleles ◽  
Structural Variations ◽  
Marine Bivalves ◽  
Transmissible Cancer ◽  
New Hosts ◽  
Genetic Chimerism ◽  
Low Prevalence

Transmissible cancers are parasitic malignant cell lineages that acquired the ability to infect new hosts from the same species, or sometimes related species. First described in dogs and Tasmanian devils, transmissible cancers were later discovered in some marine bivalves affected by a leukemia-like disease. In Mytilus mussels, two lineages of Bivalve Transmissible Neoplasia (BTN), both emerged in a M. trossulus founder individual, have been described to date (MtrBTN1 and MtrBTN2). Here, we performed an extensive screening of genetic chimerism, a hallmark of transmissible cancer, by genotyping hundred SNPs of thousands of European Mytilus mussels. The genetic analysis allowed us to simultaneously obtain the genotype of hosts -M. edulis, M. galloprovincialis or hybrids- and the genotype of tumors of heavily infected individuals. In addition, a subset of individuals were systematically genotyped and analysed by histology in order to screen for possible non-transmissible cancers. We detected MtrBTN2 at low prevalence in M. edulis, and also in M. galloprovincialis and hybrids although at a much lower prevalence. No MtrBTN1 or new BTN were found but a few individuals with non-transmissible neoplasia were observed at a single polluted site on the same sampling date. We observed a diversity of MtrBTN2 genotypes that appeared more introgressed or more ancestral than MtrBTN1 and reference healthy M. trossulus individuals. The observed polymorphism is most likely due to somatic null alleles caused by structural variations or point mutations in primer-binding sites leading to enhanced detection of the host alleles. Despite low prevalence, two divergent sublineages, confirmed by mtCOI sequences, are co-spreading in the same geographic area, suggesting a complex diversification of MtrBTN2 since its emergence and host species shift.

scholarly journals SVFX: a machine-learning framework to quantify the pathogenicity of structural variants

2019 ◽  
Author(s):  
Sushant Kumar ◽  
Arif Harmanci ◽  
Jagath Vytheeswaran ◽  
Mark B. Gerstein
Keyword(s):  
Machine Learning ◽  
Large Scale ◽  
Three Dimensional ◽  
Point Mutations ◽  
Dimensional Structure ◽  
Rapid Decline ◽  
Ras Signaling ◽  
Cancer Genes ◽  
Structural Variations ◽  
Pathogenic Variants

AbstractA rapid decline in sequencing cost has made large-scale genome sequencing studies feasible. One of the fundamental goals of these studies is to catalog all pathogenic variants. Numerous methods and tools have been developed to interpret point mutations and small insertions and deletions. However, there is a lack of approaches for identifying pathogenic genomic structural variations (SVs). That said, SVs are known to play a crucial role in many diseases by altering the sequence and three-dimensional structure of the genome. Previous studies have suggested a complex interplay of genomic and epigenomic features in the emergence and distribution of SVs. However, the exact mechanism of pathogenesis for SVs in different diseases is not straightforward to decipher. Thus, we built an agnostic machine-learning-based workflow, called SVFX, to assign a “pathogenicity score” to somatic and germline SVs in various diseases. In particular, we generated somatic and germline training models, which included genomic, epigenomic, and conservation-based features for SV call sets in diseased and healthy individuals. We then applied SVFX to SVs in six different cancer cohorts and a cardiovascular disease (CVD) cohort. Overall, SVFX achieved high accuracy in identifying pathogenic SVs. Moreover, we found that predicted pathogenic SVs in cancer cohorts were enriched among known cancer genes and many cancer-related pathways (including Wnt signaling, Ras signaling, DNA repair, and ubiquitin-mediated proteolysis). Finally, we note that SVFX is flexible and can be easily extended to identify pathogenic SVs in additional disease cohorts.

scholarly journals Population structure of the New Zealand whelk, Cominella glandiformis (Gastropoda: Buccinidae), suggests sporadic dispersal of a direct developer

2020 ◽  
Vol 130 (1) ◽  
pp. 49-60
Author(s):  
Kirsten M Donald ◽  
Graham A McCulloch ◽  
Ludovic Dutoit ◽  
Hamish G Spencer
Keyword(s):  
Population Structure ◽  
Gene Flow ◽  
New Zealand ◽  
Genetic Structure ◽  
Geographic Area ◽  
Null Alleles ◽  
Phylogeographic Structure ◽  
Large Geographic Area ◽  
Oceanic Currents ◽  
Minimal Evidence

Abstract We examined phylogeographic structure in the direct-developing New Zealand endemic intertidal mud whelk, Cominella glandiformis. Two hundred and ninety-six whelks from 12 sites were collected from sheltered shores around New Zealand’s four largest islands (North Island, South Island, Stewart Island and Chatham Island), encompassing the geographical range of this species. Despite being direct developers, gene flow among C. glandiformis populations may occur over short distances by adult floating, and over larger distances by rafting of egg masses. Primers were developed to amplify variable microsatellite regions at six loci. All loci were variable, with 8–34 alleles/loci. Observed and expected heterozygosities were high across all alleles, with minimal evidence of null alleles. The average number of alleles varied from 3.5 (Chatham Island) to 7.5 (Waitemata Harbour). Strong genetic structure was evident, with distinct ‘eastern’ and ‘western’ groups. Each group extended over a large geographic area, including regions of unsuitable habitat, but were linked by oceanic currents. We suggest that the intraspecific geographic genetic structure in C. glandiformis has arisen due a combination of ocean currents (promoting gene flow between geographically distant regions) and upwelling areas (limiting gene flow between certain regions).

Patterns of digenean parasitism of bivalves from the Great Barrier Reef and associated waters

2005 ◽  
Vol 56 (4) ◽  
pp. 387 ◽  
Author(s):  
Nathan J. Bott ◽  
John M. Healy ◽  
Thomas H. Cribb
Keyword(s):  
Great Barrier Reef ◽  
Trematode Species ◽  
Barrier Reef ◽  
Bivalve Species ◽  
Marine Waters ◽  
New Host ◽  
Lizard Island ◽  
Marine Bivalves ◽  
Low Prevalence ◽  
Host Parasite

Digenean parasites of marine bivalves are relatively poorly known, particularly in Australia. We surveyed 2256 bivalve individuals (47 species, 17 families) from Queensland marine waters incorporating south-east Queensland, Heron Island (southern Great Barrier Reef) and Lizard Island (northern Great Barrier Reef). Infections of trematode species from three families, Bucephalidae, Gorgoderidae and Monorchiidae, were found. Overall prevalence of infection was 2.3%. The Bucephalidae was the most commonly found family; 11 species were found in Tellinidae, Ostreidae, Isognomonidae and Spondylidae – the latter two previously unknown as hosts for bucephalids. A single gorgoderid infection was found in a venerid, Lioconcha castrensis. Five species of monorchiids were found from Tellinidae and Lucinidae. All infections are new host/parasite records. No infections were found in 35 of the 47 bivalve species sampled. The generally low prevalence of infection by digeneans of bivalves suggests that it is unlikely that any of the species reported here are seriously damaging to bivalve populations in these waters. We deduce that, at best, we have some life-cycle information but no actual identifications for 10% of the species of trematodes that infect bivalves of Queensland marine waters.

scholarly journals Aberrant (pro)renin receptor expression induces genomic instability in pancreatic ductal adenocarcinoma through upregulation of SMARCA5/SNF2H

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Yuki Shibayama ◽  
Kazuo Takahashi ◽  
Hisateru Yamaguchi ◽  
Jun Yasuda ◽  
Daisuke Yamazaki ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Genomic Instability ◽  
Chromosomal Abnormalities ◽  
Point Mutations ◽  
Nuclear Bodies ◽  
Receptor Expression ◽  
Ductal Adenocarcinoma ◽  
Structural Variations ◽  
Aberrant Expression ◽  
Genome Level

Abstract(Pro)renin receptor [(P)RR] has a role in various diseases, such as cardiovascular and renal disorders and cancer. Aberrant (P)RR expression is prevalent in pancreatic ductal adenocarcinoma (PDAC) which is the most common pancreatic cancer. Here we show whether aberrant expression of (P)RR directly leads to genomic instability in human pancreatic ductal epithelial (HPDE) cells. (P)RR-expressing HPDE cells show obvious cellular atypia. Whole genome sequencing reveals that aberrant (P)RR expression induces large numbers of point mutations and structural variations at the genome level. A (P)RR-expressing cell population exhibits tumour-forming ability, showing both atypical nuclei characterised by distinctive nuclear bodies and chromosomal abnormalities. (P)RR overexpression upregulates SWItch/Sucrose Non-Fermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (SMARCA5) through a direct molecular interaction, which results in the failure of several genomic stability pathways. These data reveal that aberrant (P)RR expression contributes to the early carcinogenesis of PDAC.

Epidemiologic Study of Infant Botulism in Pennsylvania: Report of the Infant Botulism Study Group

PEDIATRICS ◽  
1985 ◽  
Vol 75 (5) ◽  
pp. 928-934
Author(s):  
Sarah S. Long
Keyword(s):  
Risk Factors ◽  
Epidemiologic Study ◽  
Geographic Area ◽  
The United States ◽  
Family Characteristics ◽  
Related Factors ◽  
Related Risk ◽  
Potential Risk Factors ◽  
Infant Botulism ◽  
Low Prevalence

The majority of the almost 400 confirmed cases of infant botulism in the United States have occurred in California, Pennsylvania, and Utah. In Pennsyvania, 44 of 53 (83%) cases occurred within a geographic area of Southeastern Pennsylvania which represents one tenth of the Commonwealth's area and one third of the population at risk for infant botulism. In Southeastern Pennsylvania, a map of the residences of cases circumscribes a discrete ring around Philadelphia. A case-control study performed to seek host-related risk factors, identifies the significant associations of botulism with infants who are white, breast-fed, and born at term into two-parent families with hospitalization insurance. County control studies were performed to identify differences in host-related factors between areas of high and low prevalence of botulism. Although some "protection" could be afforded Philadelphia infants by their feeding and family characteristics, the differences in case rates between Philadelphia and the botulism "ring counties" cannot be explained entirely by host-related factors. Further, the absence of botulism in counties just outside of the botulism "ring," where infants were found to have identical potential risk factors, suggests that an uneven distribution of botulinal spores in the environment is the most significant determinant of case rate.

scholarly journals Heterozygosity and growth in the marine bivalve Spisula ovalis: testing alternative hypotheses

1997 ◽  
Vol 70 (3) ◽  
pp. 215-223 ◽  
Author(s):  
PATRICE DAVID ◽  
BERNARD DELAY ◽  
PHILIPPE JARNE
Keyword(s):  
Age And Growth ◽  
Null Alleles ◽  
Marine Bivalve ◽  
Multilocus Genotype ◽  
Simple Explanation ◽  
Specific Effects ◽  
Marine Bivalves ◽  
Alternative Hypotheses ◽  
Mean Fitness ◽  
The Relationship

Allozyme-associated heterosis has been repeatedly observed in marine bivalves, but its genetic origin remains debatable. A simple explanation is direct overdominance at the enzyme loci scored. An alternative is associative overdominance due to partial inbreeding, affecting the whole genome. The two hypotheses yield different predictions concerning (i) locus-specific effects, (ii) the relationship between heterozygosity and the variance in fitness, and (iii) the expected form of the relationship between the multilocus genotype and mean fitness. The relationship between heterozygosity and growth, a component of fitness, is here analysed in Spisula ovalis (1669 individuals, 9 loci), using statistical models designed to test these predictions. In contrast to most other bivalves, S. ovalis shells display clear annual growth lines allowing accurate quantification of individual age and growth. Our results show (i) that there is no evidence for locus-specific effects, (ii) that the variance in growth decreases significantly when heterozygosity increases, and (iii) that growth is better predicted by a genetic variable optimized for inbreeding than by a variable optimized for overdominance. In addition, the heterozygosity–growth relationship displays a significant variation among annual cohorts, being more pronounced in young cohorts. Although the need to pool alleles and the occurrence of null alleles may limit the efficiency of some of the models used (especially for result (iii)), our results suggest that the heterozygosity–growth relationship is due to inbreeding effects.

scholarly journals Helicobacter pylori Primary and Secondary Genotypic Resistance to Clarithromycin and Levofloxacin Detection in Stools: A 4-Year Scenario in Southern Italy

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 723
Author(s):  
Giuseppe Losurdo ◽  
Floriana Giorgio ◽  
Maria Pricci ◽  
Bruna Girardi ◽  
Francesco Russo ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Point Mutations ◽  
Amino Acid Position ◽  
Geographic Area ◽  
23S Rrna ◽  
Genotypic Resistance ◽  
Secondary Resistance ◽  
Resistant Strains ◽  
Polymerase Chain ◽  
H Pylori

Antibiotic resistance has become an emerging problem for treating Helicobacter pylori (H. pylori) infection. Clarithromycin and levofloxacin are two key antibiotics used for its eradication. Therefore, we reviewed our experience with genotypic resistance analysis in stools to both clarithromycin and levofloxacin in the last four years to evaluate time trends, both in naive and failure patients. Patients collected a fecal sample using the THD fecal test device. Real-time polymerase chain reaction was performed to detect point mutations conferring resistance to clarithromycin (A2142C, A2142G, and A2143G in 23S rRNA) and levofloxacin (substitutions at amino acid position 87 and 91 of gyrA). One hundred and thirty-five naive patients were recruited between 2017–2020. Clarithromycin resistance was detected in 37 (27.4%). The time trend did not show any significant variation from 2017 to 2020 (p = 0.33). Primary levofloxacin resistance was found in 26 subjects (19.2%), and we observed a dramatic increase in rates from 2017 (10%) to 2018 (3.3%), 2019 (20%), and 2020 (37.8%). Ninety-one patients with at least one eradication failure were recruited. Secondary resistance to clarithromycin and levofloxacin was found in 59 (64.8%) and 45 patients (59.3%), respectively. In conclusion, our geographic area has a high risk of resistance to clarithromycin. There is also a progressive spreading of levofloxacin-resistant strains.

scholarly journals Therapeutic Implication of Genomic Landscape of Adult Metastatic Sarcoma

2019 ◽  
pp. 1-25 ◽  
Author(s):  
Xiaolan Feng ◽  
Erin Pleasance ◽  
Eric Y. Zhao ◽  
Tony Ng ◽  
Jasleen K. Grewal ◽  
...  
Keyword(s):  
Copy Number ◽  
Large Scale ◽  
Therapeutic Potential ◽  
Point Mutations ◽  
Therapeutic Targets ◽  
Genomic Analysis ◽  
Copy Number Variations ◽  
Cancer Genes ◽  
Structural Variations ◽  
Metastatic Sarcoma

PURPOSE This study investigated therapeutic potential of integrated genome and transcriptome profiling of metastatic sarcoma, a rare but extremely heterogeneous group of aggressive mesenchymal malignancies with few systemic therapeutic options. METHODS Forty-three adult patients with advanced or metastatic non-GI stromal tumor sarcomas of various histology subtypes who were enrolled in the Personalized OncoGenomics program at BC Cancer were included in this study. Fresh tumor tissues along with blood samples underwent whole-genome and transcriptome sequencing. RESULTS The most frequent genomic alterations in this cohort are large-scale structural variation and somatic copy number variation. Outlier RNA expression as well as somatic copy number variations, structural variations, and small mutations together suggest the presence of one or more potential therapeutic targets in the majority of patients in our cohort. Point mutations or deletions in known targetable cancer genes are rare; for example, tuberous sclerosis complex 2 provides a rationale for targeting the mammalian target of rapamycin pathway, resulting in a few patients with exceptional clinical benefit from everolimus. In addition, we observed recurrent 17p11-12 amplifications, which seem to be a sarcoma-specific event. This may suggest that this region harbors an oncogene(s) that is significant for sarcoma tumorigenesis. Furthermore, some sarcoma tumors carrying a distinct mutational signature suggestive of homologous recombination deficiency seem to demonstrate sensitivity to double-strand DNA–damaging agents. CONCLUSION Integrated large-scale genomic analysis may provide insights into potential therapeutic targets as well as novel biologic features of metastatic sarcomas that could fuel future experimental and clinical research and help design biomarker-driven basket clinical trials for novel therapeutic strategies.

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