Complete sequence analysis of mitochondrial DNA of  aplastic anemia patients.
This study was primarily undertaken to test the  hypothesis that mitochondrial DNA (mtDNA) mutations may be associated with  aplastic anemia (AA). We analyzed mtDNA sequences from 15 patients with AA. The  samples were obtained from bone marrow, and patients' oral epithelial cells  were collected for normal tissue comparison. Total DNA was amplified by PCR after  extraction, and these segments were then sent for sequencing. The results were  compared with those of oral epithelial tissues as well as mtDNA sequences in  the revised Cambridge Reference Sequence (rCRS) database. We detected 61  heteroplasmic mutations in 11 genes, including those encoding NADH  dehydrogenase (ND)1-2 and 4-6, tRNA glutamic  acid (TRNE), ribosomal RNA (RNR) 1 and 2,  cytochrome c oxidase (COX1), cytochrome b (CYTB), and tRNA  glycine (TRNG); mutation rates were particularly high in ND2 (34.4%) and ND4 (21.3%) in  the patients' mtDNA genomes. The products of these genes are involved in  oxidation in the respiratory chain, and a large number of homoplasmic mutations  were found. Interestingly, these 162 polymorphisms were mostly in the D-loop  DNA structure (54.3%), in which numerous mutations associated with leukemia and  myelodysplastic syndromes are found. We conclude that functional impairment of  the mitochondrial respiratory chain induced by mutation may be an important  reason for hematopoietic failure in AA patients.
Department of Hematology, Affiliated Hospital, Shandong University of Traditional Chinese Medicine, Jinan, China. cdz45@163.com
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D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D005260:Female; D050259:Genes, Mitochondrial / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods*
D004272:DNA, Mitochondrial