Approaches to identify genes for complex human diseases: Lessons from Mendelian disorders

被引:44
作者
Dean, M [1 ]
机构
[1] NCI, Lab Genom Divers, Frederick, MD 21702 USA
关键词
complex disease; genotype-phenotype; Mendelian; non-Mendelian; mutation analysis;
D O I
10.1002/humu.10259
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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. Published 2003 Wiley-Liss, Inc.
引用
收藏
页码:261 / 274
页数:14
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