TRNA-Leu (UUR) gene haplotypes observed in canine mammary gland tumours and its deleterious effect assessment according to the comparative analysis with TRNL1 human gene

The aetiology and pathogenesis of many canine tumours are likely to be similar to cancers found in humans. This study aimed to present a plausible link between changes in tRNA-Leu (UUR) gene and the carcinogenesis process in dogs with mammary gland tumours. The whole mitochondrial DNA (mtDNA) isolated from blood and tumour tissues of 13 dogs with malig-nant mammary gland tumours was sequenced. The conducted analyses showed two polymor-phisms: m.2678_2679insG and m.2683G>A, located in tRNA-Leu (UUR) gene. We compared the reference sequences of human and canine mtDNA with the use of alignment algorithms in order to find similarities. The homology between human TRNL1 and canine tRNA Leu (UUR) gene was 84%. After resequencing of the whole mitochondrial DNA genome with the use of NGS technology, two polymorphisms in two haplotypes were identified: m.2683G>A (observed in 18 out of 27 samples) and m.2678_2679insG (27 out of 27 samples). The polymorphism m.2683G>A corresponded with deleterious change at m.3243A>G, which is linked with MELAS (Mitochondrial Encephalomyopathy, Lactis Acidose, Stroke-like episodes) syndrome and with different types of cancers in humans as well. The comparative analysis of TRNL1 and tRNA Leu (UUR) led us to hypothesise that the polymorphisms m.2678_2679insG and m.2683G>A might influence on dog’s condition and might be linked with tumorigenesis as it was observed in humans.多种犬类肿瘤的病因学与发病机制，或与人类癌症相似。本研究旨在阐明犬乳腺肿瘤患者体内亮氨酸转运RNA（UUR）基因 (tRNA-Leu (UUR))的变化与癌变进程之间的潜在关联。研究人员对13例恶性乳腺肿瘤犬的血液及肿瘤组织中提取的全线粒体DNA（mitochondrial DNA, mtDNA）进行了测序。分析结果显示，亮氨酸转运RNA（UUR）基因中存在两处多态性位点：m.2678_2679insG与m.2683G>A。研究人员通过比对算法比对人类与犬类的线粒体DNA参考序列，以寻找二者的同源性，结果显示人类TRNL1基因与亮氨酸转运RNA（UUR）基因的同源性为84%。随后通过下一代测序技术（next-generation sequencing, NGS）对全线粒体DNA基因组进行重测序，在2个单倍型中鉴定出两处多态性位点：m.2683G>A（27份样本中18份可观测到该位点）与m.2678_2679insG（27份样本中均观测到该位点）。其中，多态性位点m.2683G>A与m.3243A>G的有害突变相对应，该突变与人类线粒体脑肌病伴乳酸酸中毒和卒中样发作综合征（MELAS, Mitochondrial Encephalomyopathy, Lactis Acidose, Stroke-like episodes）以及多种人类癌症均存在关联。通过对人类TRNL1基因与亮氨酸转运RNA（UUR）基因的比较分析，研究人员推测，m.2678_2679insG与m.2683G>A这两处多态性位点可能会影响犬的健康状况，并可能与肿瘤发生相关，这与人类中的观测结果一致。