Thomas R, Bridge W, Benke K, Breen M
Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, UK.
Cytogenet Genome Res. 2003;102(1-4):249-53. doi: 10.1159/000075757.
An extensive number of genes have been implicated in the initiation and progression of human cancers, aiding our understanding of the genetic aetiology of this highly heterogeneous disease. In order to facilitate extrapolation of such information between species, we have isolated and physically mapped the canine orthologues of 25 well-characterised human cancer-related genes. The identity of PCR products representing each canine gene marker was first confirmed by DNA sequencing analysis. Each product was then radiolabelled and used to screen a genomic BAC library for the domestic dog. The chromosomal location of each positive clone in the canine karyotype was determined by fluorescence in situ hybridisation (FISH) onto canine metaphase preparations. Of the 25 genes, the FISH localisation of 21 correlated fully with that expected on the basis of known regions of conserved synteny between the human and canine genomes. Three correlated less closely, and the chromosomal location of the remaining marker showed no apparent correlation with current comparative mapping data. In addition to generating useful comparative mapping information, this panel of markers will act as a valuable resource for detailed study of candidate genes likely to be involved in tumourigenesis, and also forms the basis of a canine cancer-gene genomic microarray currently being developed for the study of unbalanced genomic aberrations in canine tumours.
大量基因与人类癌症的发生和发展有关，这有助于我们理解这种高度异质性疾病的遗传病因。为了便于在物种间推断此类信息，我们分离并物理定位了25个特征明确的人类癌症相关基因的犬类直系同源基因。首先通过DNA测序分析确认了代表每个犬类基因标记的PCR产物的身份。然后对每个产物进行放射性标记，并用于筛选家犬的基因组BAC文库。通过荧光原位杂交（FISH）对犬中期染色体标本进行检测，确定了每个阳性克隆在犬核型中的染色体位置。在这25个基因中，21个基因的FISH定位与基于人类和犬类基因组已知保守同线性区域预期的定位完全相关。三个基因的相关性稍弱，其余标记的染色体位置与当前的比较图谱数据没有明显相关性。除了生成有用的比较图谱信息外，该标记 panel 将作为详细研究可能参与肿瘤发生的候选基因的宝贵资源，也是目前正在开发的用于研究犬类肿瘤中基因组不平衡畸变的犬类癌症基因基因组微阵列的基础。
