Genomic Restructuring in the Tasmanian Devil Facial Tumour: Chromosome Painting and Gene Mapping Provide Clues to Evolution of a Transmissible Tumour
| Autor: | Hannah S. Bender, Malcolm A. Ferguson-Smith, Robyn Taylor, Anthony T. Papenfuss, Janine E. Deakin, Patricia C. M. O’Brien, Katherine Belov, Elizabeth P. Murchison, Willem Rens, Anne-Maree Pearse, Katrina M. Morris, Jennifer A. Marshall Graves, Chris T. Amemiya, Yuanyuan Cheng, Andrew Stuart |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
lcsh:QH426-470 Devil facial tumour disease Chromosomal rearrangement Biology Animal Diseases Chromosome Painting Cytogenetics 03 medical and health sciences 0302 clinical medicine Species Specificity Gene mapping Genetics medicine Animals Molecular Biology Genetics (clinical) Ecology Evolution Behavior and Systematics X chromosome 030304 developmental biology Gene Rearrangement 0303 health sciences Genome Chromosome Mapping Chromosome Karyotype Genomics Gene rearrangement medicine.disease Clone Cells lcsh:Genetics Marsupialia Chromosome 4 Karyotyping 030220 oncology & carcinogenesis Facial Neoplasms Neoplasm Transplantation Research Article |
| Zdroj: | PLoS Genetics, Vol 8, Iss 2, p e1002483 (2012) PLoS Genetics |
| ISSN: | 1553-7404 |
| DOI: | 10.1371/journal.pgen.1002483 |
| Popis: | Devil facial tumour disease (DFTD) is a fatal, transmissible malignancy that threatens the world's largest marsupial carnivore, the Tasmanian devil, with extinction. First recognised in 1996, DFTD has had a catastrophic effect on wild devil numbers, and intense research efforts to understand and contain the disease have since demonstrated that the tumour is a clonal cell line transmitted by allograft. We used chromosome painting and gene mapping to deconstruct the DFTD karyotype and determine the chromosome and gene rearrangements involved in carcinogenesis. Chromosome painting on three different DFTD tumour strains determined the origins of marker chromosomes and provided a general overview of the rearrangement in DFTD karyotypes. Mapping of 105 BAC clones by fluorescence in situ hybridisation provided a finer level of resolution of genome rearrangements in DFTD strains. Our findings demonstrate that only limited regions of the genome, mainly chromosomes 1 and X, are rearranged in DFTD. Regions rearranged in DFTD are also highly rearranged between different marsupials. Differences between strains are limited, reflecting the unusually stable nature of DFTD. Finally, our detailed maps of both the devil and tumour karyotypes provide a physical framework for future genomic investigations into DFTD. Author Summary The world's largest carnivorous marsupial, the Tasmanian devil, is threatened with extinction due to the emergence of devil facial tumour disease (DFTD), a fatal transmissible tumour. Critical loss of genetic diversity has rendered the devil vulnerable to transmission of tumour cells by grafting or transplanting the cells while biting and jaw wrestling. Initial studies of DFTD tumours revealed rearrangements among tumour chromosomes, with several missing chromosomes and four additional marker chromosomes of unknown origin. Since then, new strains of the disease have emerged and appear to be derived from the original strain. With no prior information available regarding the location of genes on normal devil chromosomes, a necessary first step towards characterisation of chromosome rearrangements in DFTD was to construct a map of the normal devil genome. This enabled us to elucidate the chromosome rearrangements in three DFTD strains. In doing so we determined the origin of the marker chromosomes and compared the three strains to determine which areas of the genome are involved in ongoing tumour evolution. Interestingly, rearrangements between strains are limited to particular genomic regions, demonstrating the unusual stability of this unique cancer. This study is therefore an important first step towards understanding the genetics of DFTD. |
| Databáze: | OpenAIRE |
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