Sellheyer Klaus, Belbin Thomas J
Department of Dermatology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
J Am Acad Dermatol. 2004 Nov;51(5):681-92; quiz 693-6. doi: 10.1016/j.jaad.2004.03.038.
The human genome project was successful in sequencing the entire human genome and ended earlier than expected. The vast genetic information now available will have far-reaching consequences for medicine in the twenty-first century. The knowledge gained from the mapping and sequencing of human genes on a genome-wide scale--commonly referred to as structural genomics--is prerequisite for studies that focus on the functional aspects of genes. A recently invented technique, known as gene chip, or DNA microarray, technology, allows the study of the function of thousands of genes at once, thereby opening the door to the new field of functional genomics. At its core, the DNA microarray utilizes a unique feature of DNA known as complementary hybridization. As such, it is not different from Southern (DNA) blot or northern (RNA) blot hybridizations, or the polymerase chain reaction, with the exception that it allows expression profiling of the entire human genome in a single hybridization experiment. The article highlights the principles, technology, and applications of DNA microarrays as they pertain to the field of dermatology and dermatopathology. The most important applications are the gene expression profiling of skin cancer, especially of melanoma. Other potential applications include gene expression profiling of inflammatory skin diseases, the mutational analysis of genodermatoses, and polymorphism screening, as well as drug development and chemosensitivity prediction. cDNA microarrays will shape the diagnostic approach of the dermatology and the dermatopathology of the future and may lead to new therapeutic options.
人类基因组计划成功地完成了整个人类基因组的测序，且比预期提前结束。如今可获取的海量遗传信息将对21世纪的医学产生深远影响。在全基因组范围内对人类基因进行图谱绘制和测序所获得的知识——通常称为结构基因组学——是专注于基因功能方面研究的先决条件。一项最近发明的技术，即基因芯片或DNA微阵列技术，能够同时研究数千个基因的功能，从而为功能基因组学这一新领域打开了大门。DNA微阵列的核心是利用了DNA一种名为互补杂交的独特特性。就此而言，它与Southern（DNA）印迹或Northern（RNA）印迹杂交，或聚合酶链反应并无不同，只是它能够在一次杂交实验中对整个人类基因组进行表达谱分析。本文重点介绍了DNA微阵列在皮肤病学和皮肤病理学领域的原理、技术及应用。最重要的应用是皮肤癌尤其是黑色素瘤的基因表达谱分析。其他潜在应用包括炎症性皮肤病的基因表达谱分析、遗传性皮肤病的突变分析、多态性筛查，以及药物研发和化学敏感性预测。cDNA微阵列将塑造未来皮肤病学和皮肤病理学的诊断方法，并可能带来新的治疗选择。
