Variations on a Gene

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Although President Bill Clinton surely had something in mind during his 2000 State of the Union address when he asked the nation to "celebrate our diversity," insights into human diversity at the molecular level are promising to speed drug discovery and revolutionize medicine to mark- edly improve human health. Individuals differ at one in 1,000 base pairs, which adds up to a whopping number of human genetic variations when applied to the roughly three billion base pairs of the human genome.¹ These alterations take the form of base changes, deletions, additions, or chromosomal rearrangements. Although many of these changes have no deleterious effects, some mutations cause or increase susceptibility to disease while others may alter the body's response to disease-fighting drugs.

Mutations affecting drug responses can occur at several levels: in the direct target of the drug, in a signaling pathway, or in drug-metabolizing enzymes. Stratifying patients based...