Dean Michael
Laboratory of Genomic Diversity, National Cancer Institute-Frederick, Frederick, Maryland 21702, USA.
Hum Mutat. 2003 Oct;22(4):261-74. doi: 10.1002/humu.10259.
The focus of most molecular genetics research is the identification of genes involved in human disease. In the 20th century, genetics progressed from the rediscovery of Mendel's Laws to the identification of nearly every Mendelian genetic disease. At this pace, the genetic component of all complex human diseases could be identified by the end of the 21st century, and rational therapies could be developed. However, it is clear that no one approach will identify the genes for all diseases with a genetic component, because multiple mechanisms are involved in altering human phenotypes, including common alleles with small to moderate effects, rare alleles with moderate to large effects, complex gene-gene and gene-environment interactions, genomic alterations, and noninherited genetic effects. The knowledge gained from the study of Mendelian diseases may be applied to future research that combines linkage-based, association-based, and sequence-based approaches to detect most disease alleles. The technology to complete these studies is at hand and requires that modest improvements be applied on a wide scale. Improved analytical tools, phenotypic characterizations, and functional analyses will enable complete understanding of the genetic basis of complex diseases.
大多数分子遗传学研究的重点是确定与人类疾病相关的基因。在20世纪，遗传学从孟德尔定律的重新发现发展到几乎识别出每一种孟德尔遗传病。按照这个速度，到21世纪末，所有复杂人类疾病的遗传成分都可能被识别出来，并且可以开发出合理的治疗方法。然而，很明显，没有一种方法能识别出所有具有遗传成分疾病的基因，因为改变人类表型涉及多种机制，包括具有小到中等效应的常见等位基因、具有中等至大效应的罕见等位基因、复杂的基因-基因和基因-环境相互作用、基因组改变以及非遗传遗传效应。从孟德尔疾病研究中获得的知识可应用于未来的研究，这些研究结合基于连锁、基于关联和基于序列的方法来检测大多数疾病等位基因。完成这些研究的技术已经具备，只需要在广泛范围内进行适度改进。改进的分析工具、表型特征描述和功能分析将使人们能够全面了解复杂疾病的遗传基础。
