Kiechle F L, Zhang X, Malinski T
Department of Clinical Pathology, William Beaumont Hospital, Royal Oak, MI 48073-6769, USA.
Ann Clin Lab Sci. 1999 Jan-Mar;29(1):59-77.
Human cells contain deoxyribonucleic acid in mitochondria and nuclei. Human diseases may be caused by mutations in mitochondrial DNA, nuclear DNA or both. The volume of work performed in the diagnostic molecular pathology laboratory will continue to grow as more disease-related mutations are discovered. Many factors will influence the diagnostic molecular pathology laboratory in the 21st century, such as future clinical laboratory organization, amplification methods, specimen integrity, ethical guidelines and opportunities to expand service. In the evaluation of a patient suspected of a mitochondrial DNA mutation, care must be exercised in the selection of a primer for amplification and of the specimen to be examined for the mutation. The uneven distribution of normal and abnormal mitochondrial DNA within the various tissues (heteroplasmy) may result in a normal mitochondrial DNA sequence if the wrong tissue is examined. The presence of mitochondrial-like sequences (pseudogenes) within nuclear DNA may result in amplification of nuclear genes if generic primers are used to duplicate a mitochondrial DNA gene. Diabetes mellitus is a heterogeneous disease with mutations occurring in a variety of proteins leading to either prereceptor, receptor or postreceptor defects. In this example, the diagnostic molecular pathology laboratory may be asked to define the specific genotype a specific patient with this common phenotype may possess.
人类细胞的线粒体和细胞核中都含有脱氧核糖核酸。人类疾病可能由线粒体DNA、核DNA或两者的突变引起。随着发现更多与疾病相关的突变，诊断分子病理学实验室的工作量将持续增加。21世纪，许多因素将影响诊断分子病理学实验室，如未来临床实验室的组织架构、扩增方法、样本完整性、伦理准则以及拓展服务的机会等。在评估疑似线粒体DNA突变的患者时，选择用于扩增的引物和检测突变的样本时必须格外小心。由于正常和异常线粒体DNA在不同组织中的分布不均（异质性），如果检查了错误的组织，可能会得到正常的线粒体DNA序列。如果使用通用引物复制线粒体DNA基因，核DNA中存在的线粒体样序列（假基因）可能会导致核基因的扩增。糖尿病是一种异质性疾病，多种蛋白质发生突变会导致受体前、受体或受体后缺陷。在这个例子中，诊断分子病理学实验室可能会被要求确定具有这种常见表型的特定患者可能拥有的特定基因型。
