scholarly journals Multiple mutations acquired into canine RecQ-like helicases encoded by the aneuploid genome of transmissible sarcoma

2018 ◽  
Author(s):  
Wadim J. Kapulkin
Keyword(s):  
Genomic Structure ◽  
Single Gene ◽  
Domestic Dog ◽  
Dna Helicases ◽  
Structural Aberrations ◽  
Canine Transmissible Venereal Tumour ◽  
Multiple Hit ◽  
Genetic Events ◽  
Transmissible Venereal Tumour

ABSTRACTSticker sarcoma – a highly aneuploid, contagious neoplasm circulating in a domestic dog population - is broadly referred as a canine transmissible venereal tumour (CTVT). The karyotype of transmissible Sticker sarcoma appears as a collage of numerical and structural aberrations; the CTVT genome represents the generalized but stable neoplastic aneuploidy of monoclonal origins. Presented is an analysis of genetic events and variants underlying the aneuploid genomic structure of Sticker sarcoma described previously by Murchison et al. (2014) and Decker et al. (2015). Here we explored the above CTVT genomic compendia and mined the existing data - specifically looking for cases of convergence of multiple non-synonymous variants onto a single gene - the mutational patterns indicative for Knudsonian ‘two-hit’ kinetics. A Table I is given, providing theoretical estimates of retaining the intact wild-type copy, expected as a function of a cumulative mutational convergence observed in unphased sequence consensus. We demonstrate that the two canine RecQ-like helicases: Bloom syndrome helicase and RECQL4, encoded by the aneuploid transmissible tumour, have accumulated a multitude of different mutations. Among the sets of most intensely mutated transmissible sarcoma genes, we also identified a canine FANCD2 – yet another previously unnoticed multiple-hit candidate factor. We discuss a possible role of mutated RecQ-like helicases and other cooperating factors, perceivably involved in the maintenance of the neoplastic aneuploidy. We suggest the proposed cooperative actions of CTVT RecQ-like DNA helicases could be relevant interpreting whether variants contributing to RecQ-dependent karyotypic traits, respond to selective pressures that preserve the aneuploid genomic structure of transmissible Sticker sarcoma.

scholarly journals Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Andrea Strakova ◽  
Máire Ní Leathlobhair ◽  
Guo-Dong Wang ◽  
Ting-Ting Yin ◽  
Ilona Airikkala-Otter ◽  
...  
Keyword(s):  
Negative Selection ◽  
Nuclear Genome ◽  
Cancer Evolution ◽  
Global Migration ◽  
Transmissible Cancer ◽  
Clonal Origin ◽  
Canine Transmissible Venereal Tumour ◽  
Global Population ◽  
Transmissible Venereal Tumour

Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distributions track two millennia of dog global migration. Negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and recombination has caused occasional mtDNA re-assortment. These findings implicate functional mtDNA as a driver of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution.

scholarly journals Sexual and vertical transmission of visceral leishmaniasis

2014 ◽  
Vol 8 (04) ◽  
pp. 403-407 ◽  
Author(s):  
Andreia P Turchetti ◽  
Tayse D Souza ◽  
Tatiane A Paixão ◽  
Renato L. Santos
Keyword(s):  
Visceral Leishmaniasis ◽  
Vertical Transmission ◽  
Leishmania Infantum ◽  
Vertebrate Host ◽  
Domestic Dog ◽  
Sand Flies ◽  
Phlebotomine Sand Flies

Visceral leishmaniasis (VL) is an important zoonosis caused by Leishmania infantum, which has in the domestic dog its principal vertebrate host. VL is usually transmitted by phlebotomine sand flies, however atypical routes of transmission have been described. In this review we discuss the the role of sexual and vertical transmissions, and their role in the maintenance of VL in canine populations.

Reaching Future Scientists, Consumers, & Citizens

2014 ◽  
Vol 76 (6) ◽  
pp. 379-383 ◽  
Author(s):  
Melissa A. Hicks ◽  
Rebecca J. Cline ◽  
Angela M. Trepanier
Keyword(s):  
Personalized Medicine ◽  
Genetic Basis ◽  
Genetic Disorders ◽  
Single Gene ◽  
Personal Health ◽  
Adult Onset ◽  
Biology Textbooks ◽  
Multifactorial Diseases ◽  
Single Gene Disorders

An understanding of how genomics information, including information about risk for common, multifactorial disease, can be used to promote personal health (personalized medicine) is becoming increasingly important for the American public. We undertook a quantitative content analysis of commonly used high school textbooks to assess how frequently the genetic basis of common multifactorial diseases was discussed compared with the “classic” chromosomal–single gene disorders historically used to teach the concepts of genetics and heredity. We also analyzed the types of conditions or traits that were discussed. We identified 3957 sentences across 11 textbooks that addressed multifactorial and “classic” genetic disorders. “Classic” gene disorders were discussed relatively more frequently than multifactorial diseases, as was their genetic basis, even after we enriched the sample to include five adult-onset conditions common in the general population. Discussions of the genetic or hereditary components of multifactorial diseases were limited, as were discussions of the environmental components of these conditions. Adult-onset multifactorial diseases are far more common in the population than chromosomal or single-gene disorders; many are potentially preventable or modifiable. As such, they are targets for personalized medical approaches. The limited discussion in biology textbooks of the genetic basis of multifactorial conditions and the role of environment in modifying genetic risk may limit the public’s understanding and use of personalized medicine.

scholarly journals Study of Staphylococcus aureusPathogenic Genes by Transfer and Expression in the Less Virulent Organism Streptococcus gordonii

2001 ◽  
Vol 69 (2) ◽  
pp. 657-664 ◽  
Author(s):  
P. Stutzmann Meier ◽  
J. M. Entenza ◽  
P. Vaudaux ◽  
P. Francioli ◽  
M. P. Glauser ◽  
...  
Keyword(s):  
Single Gene ◽  
Individual Factors ◽  
Gene Products ◽  
Streptococcus Gordonii ◽  
Pathogenic Role ◽  
Gain Of Function ◽  
Function Strategy

ABSTRACT Because Staphylococcus aureus strains contain multiple virulence factors, studying their pathogenic role by single-gene inactivation generated equivocal results. To circumvent this problem, we have expressed specific S. aureus genes in the less virulent organism Streptococcus gordonii and tested the recombinants for a gain of function both in vitro and in vivo. Clumping factor A (ClfA) and coagulase were investigated. Both gene products were expressed functionally and with similar kinetics during growth by streptococci and staphylococci. ClfA-positive S. gordoniiwas more adherent to platelet-fibrin clots mimicking cardiac vegetations in vitro and more infective in rats with experimental endocarditis (P < 0.05). Moreover, deletingclfA from clfA-positive streptococcal transformants restored both the low in vitro adherence and the low in vivo infectivity of the parent. Coagulase-positive transformants, on the other hand, were neither more adherent nor more infective than the parent. Furthermore, coagulase did not increase the pathogenicity ofclfA-positive streptococci when both clfA andcoa genes were simultaneously expressed in an artificial minioperon in streptococci. These results definitively attribute a role for ClfA, but not coagulase, in S. aureus endovascular infections. This gain-of-function strategy might help solve the role of individual factors in the complex the S. aureus-host relationship.

Treatment of Canine Transmissible Venereal Tumour using Different Surgico-chemotherapeutic Protocols

2021 ◽  
Author(s):  
Nutan Punchkande ◽  
Rukmani Dewangan ◽  
Raju Sharda ◽  
D. Jolhe ◽  
Dhaleshwari Sahu ◽  
...  
Keyword(s):  
Biochemical Parameters ◽  
Histopathological Examination ◽  
Surgical Excision ◽  
Treatment Protocols ◽  
Post Surgery ◽  
Vincristine Sulphate ◽  
Group A ◽  
Group B ◽  
Canine Transmissible Venereal Tumour ◽  
Transmissible Venereal Tumour

Background: Canine transmissible venereal tumour (CTVT) also known as infectious sarcoma, venereal granuloma, transmissible lymphosarcoma or sticker tumour is usually transmitted through coitus and mainly affects the external genitalia of young sexually matured dogs. Surgery, chemotherapy, radiotherapy and immunotherapy are considered as effective treatment protocols. Therefore, depending upon the availability present study was designed to investigate the efficacy of different surgico-chemotherapeutic protocols for treatment of canine transmissible venereal tumour.Methods: The study was conducted during January 2018 to July 2018 at the Teaching Veterinary Clinical Complex (TVCC) and Department of Veterinary Surgery and Radiology, College of Veterinary Science and A.H., Anjora, Durg (C.G.) on 18 canines of various breed, irrespective of age, sex and divided into three groups consisting 6 animals in each group. Group A was treated with surgical excision of tumour only where as Group B and Group C were treated with surgical excision of tumour followed by administration of Doxorubicin (30mg/m2) BSA and Vincristine sulphate (0.025 mg/kg) intravenously alongwith DNS at 7th and 14th post-operative days respectively. Different physiological and haemato-biochemical parameters (Hb, PCV, TLC, TPC, DLC, serum glucose, TSP, SUN, SC, ALT, AST and ALP) were recorded preoperatively, postoperatively and after chemotherapy at 10th, 30th and 60th days intervals.Result: The present investigation showed transient changes in physiological and haemato-biochemical parameters before, post surgery and post chemotherapeutic management and was within normal range. Histopathological examination revealed confluent sheet of tumour cells arranged in large round oval or polyhedral shaped distributed in tight clusters or cords. Group A showed mild to moderated reoccurrence while Group B showed minimum reoccurrence. Group C showed no reoccurrence. Thus, surgery combined with vincristine therapy is most effective for treating dogs suffering with transmissible venereal tumour.

Genes necessary for C. elegans cell and growth cone migrations

Development ◽  
1997 ◽  
Vol 124 (9) ◽  
pp. 1831-1843 ◽  
Author(s):  
W.C. Forrester ◽  
G. Garriga
Keyword(s):  
Cell Fate ◽  
Single Gene ◽  
Growth Cones ◽  
Cell Fate Specification ◽  
Fate Specification ◽  
C Elegans ◽  
Final Destination ◽  
Multiple Cell

The migrations of cells and growth cones contribute to form and pattern during metazoan development. To study the mechanisms that regulate cell motility, we have screened for C. elegans mutants defective in the posteriorly directed migrations of the canal-associated neurons (CANs). Here we describe 14 genes necessary for CAN cell migration. Our characterization of the mutants has led to three conclusions. First, the mutations define three gene classes: genes necessary for cell fate specification, genes necessary for multiple cell migrations and a single gene necessary for final positioning of migrating cells. Second, cell interactions between the CAN and HSN, a neuron that migrates anteriorly to a position adjacent to the CAN, control the final destination of the HSN cell body. Third, C. elegans larval development requires the CANs. In the absence of CAN function, larvae arrest development, with excess fluid accumulating in their pseudocoeloms. This phenotype may reflect a role of the CANs in osmoregulation.

scholarly journals Loss of PTEN in Fallopian Tube Epithelium Results in Multicellular Tumor Spheroid Formation and Metastasis to the Ovary

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 884 ◽  
Author(s):  
Matthew Dean ◽  
Vivian Jin ◽  
Tova M. Bergsten ◽  
Julia R. Austin ◽  
Daniel D. Lantvit ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Single Gene ◽  
Similar Rate ◽  
Genetic Alterations ◽  
Wild Type ◽  
Spheroid Formation ◽  
Multicellular Tumor Spheroid ◽  
Ovarian Stroma

High-grade serous ovarian cancer (HGSOC) can originate in the fallopian tube and then spread to the ovary. Our objective was to evaluate the role of multicellular tumor spheroids (MTS) in ovarian metastasis. By testing a panel of murine oviductal epithelial (MOE) cells with genetic alterations mimicking those seen in HGSOC, we found that loss of PTEN allowed MTS formation under ultra-low adhesion conditions. Confirming these results in vivo, MTS-like structures were observed in the oviducts of PAX8Cre/+ PTENflox/flox mice. MOE PTENshRNA cells could incorporate up to 25% wild type cells into MTS, while higher percentages of wild type cells resulted in a loss of MTS formation. MTS formation allowed MOE PTENshRNA cells to survive better under ultra-low adhesion conditions than control cells. MTS also attached to the ovarian stroma, as would be exposed during ovulation. Interestingly, MTS more robustly cleared monolayers of murine ovarian surface epithelia than murine ovarian fibroblasts. When xenografted into the ovarian bursa, OVCAR8 MTS were able to form tumors in the ovary at a similar rate as an equal number of OVCAR8 cells grown on traditional cell culture plastic. In conclusion, loss of a single gene (PTEN) allows the fallopian tube epithelia to form MTS, which survive better under ultra-low adhesion conditions, attach to the extracellular matrix exposed during ovulation, and colonize the ovary. These results suggest that MTS may contribute to seeding of the ovary in HGSOC patients.

Sign in / Sign up

Export Citation Format

Share Document