mtDNA data mining in GenBank needs surveying.

To the Editor: Since the first sequencing of the complete humanmtDNA genome, both the sequencing techniques and the quality of commercial kits have improved greatly. This has led to a growing number of reports for complete mtDNA sequences from the fields of molecular anthropology, medical genetics, and forensic science; and there are now over 6700 complete or near-complete mtDNA sequences available for study. However, in comparison to the pioneer manual-sequencing efforts in the early nineties, the overall mtDNA data quality, especially in the medical field, is still far from satisfactory. Sequencing errors and inadvertent mistakes in the reported mtDNA data are not infrequent. Deficient mtDNA data sets of complete genomes can have important consequences for the conclusions achieved in many studies and may also pose problems for any subsequent reanalyses. Most recently, Pereira and colleagues discussed the overall picture of the mtDNA genome diversity in worldwide human populations with a comprehensive reanalysis of 5140 published complete or near-complete (lacking some control region information) mtDNA sequences. Their study represents an important advance in defining the effects of gene structures on limiting mtDNA diversity and may have valuable implications for mtDNA studies in the medical field. However, all of the data used in the study by Pereira et al. were directly retrieved from GenBank without any scrutiny for problematic or flawed data that should have been excluded. Many of the mtDNA sequences analyzed in their study have in fact already been questioned in the literature or even corrected by their authors, but unfortunately, in several instances the new corrected versions of the sequences have not been made generally available or updated in GenBank. In Table 1, we list some of the problematic data sets and single sequences used by Pereira et al. in their study. Among them is the original data set of Herrnstadt et al., which was announced by the authors as having been corrected, although the new sequences have never been entered into GenBank. Portions of those codingregion data (in either corrected or uncorrected form) were augmented by the associated control-region data and published in several papers; thus, none of these expanded data can be downloaded fromGenBank but have to be retrieved from the figures in the corresponding articles. To cite a more recent example, the African mtDNA data set published by Gonder et al. is of particularly poor quality. These sequences are incompletely recorded (as already mentioned by Behar et al.); the most extreme instance of this is the haplogroup L0k1 sequence EF184609 that lacks as many as 25 expected variants scattered along the