Molecular differences in mitochondrial DNA genomes of dogs with malignant mammary tumours
2022
Kowal, Krzysztof | Tkaczyk‐Wlizło, Angelika | Pierzchała, Mariusz | Gawor, Jan | Ślaska, Brygida
The aim of this study was to determine molecular defects in mitochondrial DNA (mtDNA) with the use of large‐scale genome analysis in malignant canine mammary gland tumours and indicate whether these changes were linked with the carcinogenesis process. With the use of the NGS technology, we sequenced 27 samples of mtDNA isolated from blood and tumours obtained from 13 dogs with mammary gland tumours. The total number of mutations and polymorphisms in the analysed mitochondrial genomes was 557. We identified 383 single nucleotide polymorphisms (SNP), 32 indels (or length polymorphisms), 4 mutations, 137 heteroplasmic positions and 1 indel mutation. The highest variability (132 changes) was observed in the variable number of tandem repeats (VNTR) region. The heteroplasmy rate in VNTR varied among individuals and even between two tumours in one organism. Our previous study resulted in determination of a probable CpG island in this region, thus it is not excluded that these changes might alter mtDNA methylation. Only the ATP8 gene was not affected by any polymorphisms or mutations, whereas the COX1 gene had the highest number of polymorphisms from all protein‐coding genes. One change m.13594G>A was detected in a region spanning two genes: ND5 and ND6, from which a deleterious effect was observed for the ND5 protein. Molecular changes were frequently observed in the TΨC loop, which is thought to interact with ribosomal RNA.
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