Table 2 of
Abu-Amero, Mol Vis 2008;
14:29-36.Table 2 of
Abu-Amero, Mol Vis 2008;
14:29-36.
Table 2. Nonsynonymous mtDNA sequence changes detected in PEG patients
In the "Base substitution type" column, Transversion=A mutation in which a purine/pyrimidine replaces a pyrimidine/purine base pair or vice versa (G:C>T:A or C:G, or A:T>T:A or C:G); Transition=A mutation in which a purine/pyrimidine base pair is replaced with a base pair in the same purine/pyrimidine relationship (A:T>G:C or C:G>T:A). Controls (%)=percent of controls with this nucleotide substitution. Previous reports of sequence variants were found in the Human Mitochondrial Genome Database (MITOMAP database), GenBank, and Medline listed publications. Interspecies conservation was assessed using the Polymorphism Phenotyping (PolyPhen) database, which determines interspecies conservation for an altered amino acid by performing alignment with all available amino acid sequences for other species, and the Mamit-tRNA website when necessary. Protean predicts and displays secondary structural characteristics. "Yes"=nucleotide change will alter protein secondary structure; "No"=change will not alter secondary structure. PolyPhen prediction of pathogenicity was assessed using the PolyPhen database. "Probably damaging" constitutes a high confidence of affecting protein function or structure. "Possibly damaging" reflects a likelihood of affecting protein function or structure, while "Benign" changes most likely lack phenotypic effect. "Unknown" means that PolyPhen could not make a prediction due to lack of data. None of these nucleotide changes was heteroplasmic. Summary; see Prediction of Pathogenicity in Methods. TM= transmembrane. N/A=not applicable because the database is not designed to predict this type of sequence change. Reported haplogroup specific NS sequence changes were excluded from Table 2 and further analysis.
Base
Nucleotide AA substitution Controls Interspecies
substitution change Location type (%) Novel conservation Protean PolyPhen Summary
------------ ------ ---------- ------------ -------- ----- ------------ ------- -------- --------------
3833 T>A L176Q TM domain Transversion 0 Yes Moderate Yes Probably Pathologic
of ND1 damaging
gene
4363 T>C N/A Anticodon Transition 0.62 No High N/A Unknown Non-pathologic
loop of
tRNA
glutamine
4385 A>G N/A In the T?C Transition 0.62 No High N/A Unknown Non-Pathologic
domain of
the tRNA
glutamine
4648 T>C F60S Outside Transition 0 Yes High Yes Probably Pathologic
the TM damaging
domain of
ND2 gene
5182 C>T T238M Outside Transition 0 Yes Low No Benign Non-Pathologic
the TM
domain of
ND2 gene
5843 A>G N/A In the Transition 1.2 No High N/A Unknown Non-pathologic
D-loop of
tRNA
tyrosine
6546 C>T L215F Outside Transition 0.62 No High No Benign Non-pathologic
the TM
domain of
COI gene
7877 A>C K98Q Outside Transversion 0 Yes High No Probably Pathologic
the TM damaging
domain of
COII gene
9103 T>C F193L Outside Transition 1.2 No Moderate No Benign Non-pathologic
the TM
domain of
ATPase 6
gene
9438 G>A G78S Outside Transition 3.14 No High No Benign Non-pathologic
the TM
domain of
COIII gene
11337 A>G N193S TM domain Transition 1.9 No Low No Benign Non-pathologic
of ND4
gene
12841 A>G I169V Outside Transition 3.1 No Low No Benign Non-pathologic
the TM
domain of
ND5 gene
13813 G>A V493I TM domain Transition 1.9 No High No Benign Non-pathologic
of ND5
gene
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