Analysis of Mitochondrial Genome from Labrador (<i>Canis lupus familiaris</i>) with Mammary Gland Tumour Reveals Novel Mutations and Polymorphisms

Kowal, Krzysztof; Ślaska, Brygida; Bownik, Adam; Horecka, Beata; Gawor, Jan; Śmiech, Anna; Tkaczyk, Angelika

doi:10.2478/aoas-2019-0027

Cited by 8 publications

(21 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The identification of variability in the mitochondrial DNA (mtDNA) sequence in dogs with diagnosed mammary tumours was presented in several reports. [3][4][5] Kowal et al described 32 polymorphisms and 15 mutations in the entire mitochondrial genome of a dog with mammary tumour. These mutations and polymorphisms may affect the functioning of mitochondria and may indicate cell adaptation to the environmental changes occurring in the carcinogenesis process.…”

mentioning

confidence: 99%

Molecular differences in mitochondrial DNA genomes of dogs with malignant mammary tumours

Kowal

Tkaczyk-Wlizło

Pierzchała

et al. 2021

Vet Comparative Oncology

Self Cite

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 99%

Molecular differences in mitochondrial DNA genomes of dogs with malignant mammary tumours

Kowal

Tkaczyk-Wlizło

Pierzchała

et al. 2021

Vet Comparative Oncology

Self Cite

View full text Add to dashboard Cite

show abstract

“…The difference in one position of the amino acid sequence had a positive effect on protein stability, i.e. the change transforms an unstable protein before the mutation into a stable one after the mutation (11). This can be verified by the theory proposed by Guruprasad et al (10), who argue that protein instability is caused by the presence of certain dipeptides in the protein structure.…”

Section: Resultsmentioning

confidence: 77%

Analysis of differences in the stability of proteins encoded in mitochondrial DNA of model organisms

Kowal¹,

Bownik²,

Tkaczyk³

et al. 2020

Medycyna Weterynaryjna

Self Cite

View full text Add to dashboard Cite

The genetic information on the structure of 37 genes, i.e. 13 respiratory chain proteins, 22 tRNA molecules, and 2 rRNA molecules, is encoded in the mitochondrial genome. Mitochondrial DNA (mtDNA) contains a non-coding region (D-loop), whose length varies among animals. Due to the lack of introns, genes in some organisms overlap, e.g. in humans, the ATP6 and ATP8 genes share 46 nucleotides and the ND4 and ND4L genes share seven nucleotides (2,8). The length of mtDNA is highly variable in different organisms, ranging from yeasts to higher eukaryotes. However, certain mtDNA properties are conserved, e.g. the presence of genes coding for highly hydrophobic and crucial components of the respiratory chain, ribosomal RNAs (rRNAs), and transfer RNAs (tRNAs), which are necessary for protein translation (5). How electron transfer is coupled to proton pumping is a major unresolved question (19). Many metabolic processes, e.g. the Krebs cycle, the urea cycle, or β-oxidation, take place in the mitochondria. Additionally, mitochondria are involved in the regulation of thermogenesis and Ca 2+ ion metabolism and exert an effect on the apoptosis process. However, the main role of mitochondria is generation of high-energy ATP in the process of oxidative phosphorylation (9). The respiratory chain consists of 5 protein complexes: NADH-ubiquinone oxidoreductase, succinate−quinone oxidoreductase, the bc1 complex, cyt c oxidase, and ATP synthase. The complexes are arranged on the internal mitochondrial membrane according to the increasing oxidoreductive potential. The difference in the potentials between the first four complexes facilitates electron transport. It results in generation of energy, which is converted by ATP synthase into high-energy phosphorus bonds (14).Approximately 0.15-2% of electrons that enter the electron transport chain (ETC) can escape the OXPHOS cycle, resulting in the formation of superoxide (22). Increased exposure to this OXPHOS-related superoxide may affect not only the mtDNA located nearby, but also proteins and lipids, resulting in impaired protein Summary The aim of this study was to describe the stability of proteins encoded in mtDNA, which are part of the OXPHOS system, in different model organisms and to define why certain proteins are more prone to be unstable than others. The in silico analyses involved 155 reference sequences of all proteins encoded in the mitochondrial DNA in twelve model organisms representing different phylogenetic groups. The amino acid sequences of the proteins were taken from the GenPept database. The bioinformatic analyses were performed in the ProtParam program. Thirty-eight of the 155 analyzed proteins exhibited instability. The greatest numbers of unstable mitochondrial proteins were detected in H. sapiens and A. mexicanum and the lowest levels were found in C. elegans. ND1 and ATP8 were the most unstable mitochondrial proteins. Proteins COX1 and COX3 did not exhibit instability in the examined group of organisms. The highest instability index values were recorded in the ...

show abstract

“…To date, most research of alterations in canine mtDNA has been focused on the hypervariable D-loop. The variability in the mtDNA D-loop sequence in dogs with diagnosed mammary tumours was identified in several reports (Grzybowska-Szatkowska et al, 2014;Surdyka et al, 2017;Kowal et al, 2019). The D-loop region is responsible for transcription, replication, and organisation of the mitochondrial genome.…”

Section: Discussionmentioning

confidence: 99%

“…The single nucleotide polymorphism (SNP) in this region may alter the functions of the electron transport chain and promote the generation of reactive oxygen species, which in turn damage the DNA structure (Brandon et al, 2006;. Kowal et al (2019) noted the highest rate of heteroplasmy in the VNTR (variable number tandem repeat) region localised in the canine D-loop.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of the tRNA-Leu (UUR) gene haplotype profile observed in canine mammary gland tumours based on comparative analysis with the MT-TL1 human gene

Kowal

Tkaczyk-Wlizło

Pierzchała

et al. 2022

Annals of Animal Science

Self Cite

View full text Add to dashboard Cite

The aetiology and pathogenesis of many canine tumours are likely to be similar to cancers found in humans. This study aimed to evaluate a plausible link between changes in the 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 malignant mammary gland tumours was sequenced. The present work is the first report showing that some polymorphisms might occur at the corresponding positions in the human and canine mtDNA genome, which in turn may provoke similar deleterious effects. The homology between the human MT-TL1 and canine tRNA-Leu (UUR) genes was 84%. After resequencing of the whole mitochondrial DNA genome with the use of the 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 m.2683G>A polymorphism corresponded to a deleterious change at m.3243A>G, which is linked with MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke-like episodes) syndrome and with different types of cancers in humans as well. The comparative analysis of MT-TL1 and tRNA-Leu (UUR) led us to hypothesise that the m.2678_2679insG and m.2683G>A polymorphisms might influence the dog’s condition and might be linked with tumourigenesis, as observed in humans.

show abstract

Analysis of Mitochondrial Genome from Labrador (Canis lupus familiaris) with Mammary Gland Tumour Reveals Novel Mutations and Polymorphisms

Cited by 8 publications

References 27 publications

Molecular differences in mitochondrial DNA genomes of dogs with malignant mammary tumours

Molecular differences in mitochondrial DNA genomes of dogs with malignant mammary tumours

Analysis of differences in the stability of proteins encoded in mitochondrial DNA of model organisms

Evaluation of the tRNA-Leu (UUR) gene haplotype profile observed in canine mammary gland tumours based on comparative analysis with the MT-TL1 human gene

Contact Info

Product

Resources

About