Chromosome Translocations in Turtles: A Biomarker in a Sentinel Animal for Ecological Dosimetry

2000 ◽  
Vol 153 (6) ◽  
pp. 752-759 ◽  
Author(s):  
B. A. Ulsh ◽  
M. C. Mühlmann-Díaz ◽  
F. W. Whicker ◽  
T. G. Hinton ◽  
J. D. Congdon ◽  
...  
Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 250
Author(s):  
Rebecca E O’Connor ◽  
Lucas G Kiazim ◽  
Claudia C Rathje ◽  
Rebecca L Jennings ◽  
Darren K Griffin

With demand rising, pigs are the world’s leading source of meat protein; however significant economic loss and environmental damage can be incurred if boars used for artificial insemination (AI) are hypoprolific (sub-fertile). Growing evidence suggests that semen analysis is an unreliable tool for diagnosing hypoprolificacy, with litter size and farrowing rate being more applicable. Once such data are available, however, any affected boar will have been in service for some time, with significant financial and environmental losses incurred. Reciprocal translocations (RTs) are the leading cause of porcine hypoprolificacy, reportedly present in 0.47% of AI boars. Traditional standard karyotyping, however, relies on animal specific expertise and does not detect more subtle (cryptic) translocations. Previously, we reported development of a multiple hybridisation fluorescence in situ hybridisation (FISH) strategy; here, we report on its use in 1641 AI boars. A total of 15 different RTs were identified in 69 boars, with four further animals XX/XY chimeric. Therefore, 4.5% had a chromosome abnormality (4.2% with an RT), a 0.88% incidence. Revisiting cases with both karyotype and FISH information, we reanalysed captured images, asking whether the translocation was detectable by karyotyping alone. The results suggest that chromosome translocations in boars may be significantly under-reported, thereby highlighting the need for pre-emptive screening by this method before a boar enters a breeding programme.


Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 235
Author(s):  
Bin Gu ◽  
Maxwell C. Hakun

NUT carcinoma (NC) is a type of aggressive cancer driven by chromosome translocations. Fusion genes between a DNA-binding protein, such as bromodomain and extraterminal domain (BET) proteins, and the testis-specific protein NUTM1 generated by these translocations drive the formation of NC. NC can develop in very young children without significant accumulation of somatic mutations, presenting a relatively clean model to study the genetic etiology of oncogenesis. However, after 20 years of research, a few challenging questions still remain for understanding the mechanism and developing therapeutics for NC. In this short review, we first briefly summarize the current knowledge regarding the molecular mechanism and targeted therapy development of NC. We then raise three challenging questions: (1) What is the cell of origin of NC? (2) How does the germline analogous epigenetic reprogramming process driven by the BET-NUTM1 fusion proteins cause NC? and (3) How will BET-NUTM1 targeted therapies be developed? We propose that with the unprecedented technological advancements in genome editing, animal models, stem cell biology, organoids, and chemical biology, we have unique opportunities to address these challenges.


2017 ◽  
Vol 59 (5) ◽  
pp. 1231-1238 ◽  
Author(s):  
Aparna Pallavajjala ◽  
Daehwan Kim ◽  
Tongbin Li ◽  
Gabriel Ghiaur ◽  
Richard J. Jones ◽  
...  

Cytogenetics ◽  
1980 ◽  
pp. 219-241
Author(s):  
Jurgen Schulz-Schaeffer

2020 ◽  
Author(s):  
Gloria Gonzalez Curto ◽  
Audrey Der Vartanian ◽  
Youcef Frarma ◽  
Line Manceau ◽  
Lorenzo Baldi ◽  
...  

AbstractThe chromosome translocations generating PAX3FOXO1 and PAX7FOXO1 chimeric proteins are the primary hallmarks of the paediatric cancer, Alveolar Rhabdomyosarcoma (ARMS). Despite the ability of these transcription factors to remodel chromatin landscapes and promote the expression of tumour driver genes, they only inefficiently promote malignant transformation in vivo. The reason for this is unclear. To address this, we developed an in ovo model to follow the response of spinal cord progenitors to PAXFOXO1s. Our data demonstrate that PAXFOXO1s, but not wild-type PAX3 and PAX7, trigger the trans-differentiation of neural cells into ARMS-like cells with myogenic characteristics. In parallel expression of PAXFOXO1s remodels the neural pseudo-stratified epithelium into a cohesive mesenchyme capable of tissue invasion. Surprisingly, gain for PAXFOXO1s, as for wild-type PAX3/7, reduces the levels of CDK-CYCLIN activity and arrests cells in G1. Introduction of CYCLIN D1 or MYCN overcomes PAXFOXO1s mediated cell cycle inhibition and promotes tumour growth. Together, our findings reveal a mechanism underpinning the apparent limited oncogenicity of PAXFOXO1 fusion transcription factors and support a neural origin for ARMS.


2021 ◽  
Author(s):  
Takaaki Yasuhara ◽  
Reona Kato ◽  
Motohiro Yamauchi ◽  
Yuki Uchihara ◽  
Lee Zou ◽  
...  

AbstractR-loops, consisting of ssDNA and DNA-RNA hybrids, are potentially vulnerable unless they are appropriately processed. Recent evidence suggests that R-loops can form in the proximity of DNA double-strand breaks (DSBs) within transcriptionally active regions. Yet, how the vulnerability of R-loops is overcome during DSB repair remains unclear. Here, we identify RAP80 as a factor suppressing the vulnerability of ssDNA in R-loops and chromosome translocations and deletions during DSB repair. Mechanistically, RAP80 prevents unscheduled nucleolytic processing of ssDNA in R-loops by CtIP. This mechanism promotes efficient DSB repair via transcription-associated end-joining dependent on BRCA1, Polθ, and LIG1/3. Thus, RAP80 suppresses the vulnerability of R-loops during DSB repair, thereby precluding genomic abnormalities in a critical component of the genome caused by deleterious R-loop processing.


2002 ◽  
Vol 22 (7) ◽  
pp. 2068-2077 ◽  
Author(s):  
Gregory S. Lee ◽  
Matthew B. Neiditch ◽  
Richard R. Sinden ◽  
David B. Roth

ABSTRACT Cleavage by the V(D)J recombinase at a pair of recombination signal sequences creates two coding ends and two signal ends. The RAG proteins can integrate these signal ends, without sequence specificity, into an unrelated target DNA molecule. Here we demonstrate that such transposition events are greatly stimulated by—and specifically targeted to—hairpins and other distorted DNA structures. The mechanism of target selection by the RAG proteins thus appears to involve recognition of distorted DNA. These data also suggest a novel mechanism for the formation of alternative recombination products termed hybrid joints, in which a signal end is joined to a hairpin coding end. We suggest that hybrid joints may arise by transposition in vivo and propose a new model to account for some recurrent chromosome translocations found in human lymphomas. According to this model, transposition can join antigen receptor loci to partner sites that lack recombination signal sequence elements but bear particular structural features. The RAG proteins are capable of mediating all necessary breakage and joining events on both partner chromosomes; thus, the V(D)J recombinase may be far more culpable for oncogenic translocations than has been suspected.


Sign in / Sign up

Export Citation Format

Share Document