Mitochondrial tRNALeu/Lys and ATPase 6/8 gene variations in spinocerebellar ataxias.
BACKGROUND
The spinocerebellar ataxias (SCA) comprise a heterogeneous group of severe late-onset neurodegenerative diseases that are promoted by the expansion of a tandem-arrayed DNA sequence that modifies the primary structure of the protein.


METHODS
Genomic DNA of 20 patients affected with SCAs was extracted from peripheral blood and screened for deletions in mitochondrial DNA (mtDNA). Sequencing of tRNA(Leu), tRNA(Lys), cytochrome oxidase II, ATPase 6/8 and NADH dehydrogenase I (NDI) genes belonging to mtDNA from patients with SCAs was also carried out to detect the presence of variations.


RESULTS
We identified cytosine-adenine-guanine (CAG) trinucleotide repeat expansions in 20 patients. Seven of these patients had at least one nucleotide change in mtDNA. In such cases, 5 nucleotide variations resulted in amino acid changes with two novel variations T8256G and G9010A.


CONCLUSIONS
SCA patients showed high levels of mtDNA variations in lymphocytes. It can be proposed that the SCA gene proteins (Ataxins) are involved in the complicated intracellular mechanisms that affect cellular organelles and their components, such as the mitochondrial genome. The instability of CAG repeats in polyglutamine diseases such as SCAs and Huntington's disease might be a causative factor in mtDNA variation or possible damage.
Safaei
Sepideh
S
Research and Sciences Campus, Azad University, Tehran, Iran.
Houshmand
Massoud
M
Banoei
Mohammad Mehdi
MM
Panahi
Mehdi Shafa Shariat
MS
Nafisi
Shahriar
S
Parivar
Kazem
K
Rostami
Maryam
M
Shariati
Parvin
P
D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution; D000067699:Ataxin-3; D000067719:Ataxin-7; D000067528:Ataxins; D015220:Calcium Channels / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics; D017931:DNA Primers; D005784:Gene Amplification; D014644:Genetic Variation; D005998:Glycine / Q000378:metabolism; D006801:Humans; D008715:Methionine / Q000235:genetics; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D012356:RNA, Transfer, Leu / Q000235:genetics*; D012357:RNA, Transfer, Lys / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D020754:Spinocerebellar Ataxias / Q000201:enzymology / Q000235:genetics*; D013912:Threonine / Q000235:genetics; D018911:Trinucleotide Repeats; D014633:Valine / Q000235:genetics; D020864:Calcium Channels, N-Type
D000409:Alanine; D000067699:Ataxin-3; D000067719:Ataxin-7; D000067528:Ataxins; D015220:Calcium Channels; D004247:DNA; D017931:DNA Primers; D005998:Glycine; D008715:Methionine; D025261:Mitochondrial Proton-Translocating ATPases; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012356:RNA, Transfer, Leu; D012357:RNA, Transfer, Lys; D012097:Repressor Proteins; D013912:Threonine; D014633:Valine; C000593829:ATXN7 protein, human; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type; C092341:ATXN3 protein, human; C513300:MT-ATP8 protein, human