TitleDiscovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease.
Publication TypeJournal Article
Year of Publication2003
AuthorsBotstein, D, Risch, N
JournalNat Genet
Volume33 Suppl
Date Published2003 Mar
KeywordsAlleles, Chromosome Mapping, Cloning, Molecular, Genetic Diseases, Inborn, Genomics, Genotype, History, 20th Century, History, 21st Century, Humans, Linkage Disequilibrium, Mutation, Phenotype, Polymorphism, Single Nucleotide

The past two decades have witnessed an explosion in the identification, largely by positional cloning, of genes associated with mendelian diseases. The roughly 1,200 genes that have been characterized have clarified our understanding of the molecular basis of human genetic disease. The principles derived from these successes should be applied now to strategies aimed at finding the considerably more elusive genes that underlie complex disease phenotypes. The distribution of types of mutation in mendelian disease genes argues for serious consideration of the early application of a genomic-scale sequence-based approach to association studies and against complete reliance on a positional cloning approach based on a map of anonymous single nucleotide polymorphism haplotypes.

Alternate JournalNat. Genet.