Accetturo Matteo, Santamaria Monica, Lascaro Daniela, Rubino Francesco, Achilli Alessandro, Torroni Antonio, Tommaseo-Ponzetta Mila, Attimonelli Marcella
Dipartimento di Biochimica e Biologia Molecolare, Università degli Studi di Bari, Bari, Italy.
Hum Mutat. 2006 Sep;27(9):965-74. doi: 10.1002/humu.20365.
Sequencing of entire human mtDNA genomes has become rapid and efficient, leading to the production of a great number of complete mtDNA sequences from a wide range of human populations. We introduce here a new statistical approach for classifying mtDNA nucleotide sites, simply by comparing the mean simple deviation (MSD) of their specific variability values estimated on continent-specific dataset sequences, without the need for any reference sequence. Excellent correspondence was observed between sites with the highest MSD values and those marking known mtDNA haplogroups. This in turn supports the classification of 81 sites (23 in Africa, eight in Asia, eight in Europe, 34 in Oceania, and eight in America) as novel markers of 47 mtDNA haplogroups not yet identified by phylogeographic studies. Not only does this approach allow refinement of mtDNA phylogeny, an essential requirement also for mitochondrial disease studies, but may greatly facilitate the discrimination of candidate disease-causing mutations from haplogroup-specific polymorphisms in mtDNA sequences of patients affected by mitochondrial disorders.
对整个人类线粒体DNA（mtDNA）基因组进行测序已变得快速且高效，这使得从广泛的人类群体中产生了大量完整的mtDNA序列。我们在此介绍一种新的统计方法，用于对mtDNA核苷酸位点进行分类，即通过比较在特定大陆数据集序列上估计的其特定变异性值的平均标准差（MSD），而无需任何参考序列。观察到具有最高MSD值的位点与标记已知mtDNA单倍群的位点之间具有极好的对应关系。这反过来支持将81个位点（非洲23个、亚洲8个、欧洲8个、大洋洲34个、美洲8个）分类为系统地理学研究尚未识别的47个mtDNA单倍群的新标记。这种方法不仅有助于完善mtDNA系统发育，这也是线粒体疾病研究的一项基本要求，而且可能极大地促进从线粒体疾病患者的mtDNA序列中的单倍群特异性多态性中区分候选致病突变。
