Bandelt Hans-Jürgen, Salas Antonio, Bravi Claudio M
Department of Mathematics, University of Hamburg, Bundesstr. 55, 20146, Hamburg, Germany.
Unidad de Genética, Instituto de Medicina Legal, Facultad de Medicina, Universidad de Santiago de Compostela, 15782, Galicia, Spain.
J Hum Genet. 2006;51(12):1073-1082. doi: 10.1007/s10038-006-0066-5. Epub 2006 Oct 5.
The hunt for pathogenic mitochondrial DNA (mtDNA) mutations is often fueled by the seeming novelty of mutations that are either nonsynonymous or affect the protein synthesis machinery in patients. In order to determine the novelty of a detected mutation, the working geneticist nearly always consults MITOMAP--often exclusively. By reanalyzing some case studies of refractory anemia with ring sideroblasts, prostate cancer, and hearing impairment, we demonstrate that the practice of solely relying on MITOMAP can be most misleading. A notorious example is the T1243C mutation, which was assessed to be novel and deemed to be associated with some (rare) disease simply because researchers did not realize that T1243C defines a deep branch in the Eurasian mtDNA phylogeny. The majority of 'novel' mutations suspected of being pathogenic are in actual fact known (and presumably neutral) polymorphisms (although unknown to MITOMAP), and this becomes glaringly evident when proper database searches and straightforward Internet queries are carried out.
对致病性线粒体DNA（mtDNA）突变的搜寻，往往是由患者中非同义突变或影响蛋白质合成机制的突变表面上的新奇性所推动的。为了确定检测到的突变的新奇性，在职遗传学家几乎总是——通常是唯一地——查阅线粒体基因组数据库（MITOMAP）。通过重新分析一些伴有环形铁粒幼细胞的难治性贫血、前列腺癌和听力障碍的病例研究，我们证明，仅依赖MITOMAP的做法可能极具误导性。一个臭名昭著的例子是T1243C突变，该突变被评估为新突变，并被认为与某种（罕见）疾病有关，仅仅是因为研究人员没有意识到T1243C定义了欧亚mtDNA系统发育中的一个深分支。大多数被怀疑具有致病性的“新”突变实际上是已知的（可能是中性的）多态性（尽管线粒体基因组数据库未知），当进行适当的数据库搜索和简单的互联网查询时，这一点就变得非常明显。
