Genetics

Contextual Analysis

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Science  11 Jan 2002:
Vol. 295, Issue 5553, pp. 235
DOI: 10.1126/science.295.5553.235h

Dopamine is a biogenic amine that functions as a neurotransmitter in central systems underlying behavior. Disturbances in dopaminergic pathways occur in many mental disorders, and the 7R allele of the human dopamine receptor gene DRD4 has been associated with an elevated incidence of attention-deficit/hyperactivity disorder (ADHD). The 7R allele is one of many such alleles (2R-11R), all of which appear to contain integral multiples of a 48-base pair segment, with single-nucleotide polymorphisms in some of the tandem repeats.

Having sequenced and analyzed 600 DRD4 alleles from a global sample, Ding et al. propose that the most common 2R-6R alleles all derive from single mutation or recombination events operating on an ancestral 4R allele. In contrast, the 7R allele, which itself could give rise to some of the less frequent alleles (5R-8R), would have required a series of at least four mutations and gene conversions. Further analysis suggests that the 7R allele may first have appeared about 40,000 years ago and subsequently been maintained due to positive selective pressure applied by the social and environmental conditions encountered during that watershed period, presumed to differ considerably from the present-day classroom where ADHD is found. — GJC,

Proc. Natl. Acad. Sci. U.S.A.99, 309 (2002).

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