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The human dopamine receptor D4 ( DRD4 ) gene contains a 48-bp variable number of tandem repeat (VNTR) in exon 3, encoding the third intracellular loop of this dopamine receptor. The  DRD4  7R allele, which seems to have a single origin, is commonly observed in various human populations and the nucleotide diversity of the  DRD4  7R haplotype at the  DRD4  locus is reduced compared to the most common  DRD4  4R haplotype. Based on these observations, previous studies have hypothesized that positive selection has acted on the  DRD4  7R allele. However, the degrees of linkage disequilibrium (LD) of the  DRD4  7R allele with single nucleotide polymorphisms (SNPs) outside the  DRD4  locus have not been evaluated. In this study, to re-examine the possibility of recent positive selection favoring the  DRD4  7R allele, we genotyped HapMap subjects for  DRD4  VNTR, and conducted several neutrality tests including long range haplotype test and iHS test based on the extended haplotype homozygosity. Our results indicated that LD of the  DRD4  7R allele was not extended compared to SNP alleles with the similar frequency. Thus, we conclude that the  DRD4  7R allele has not been subjected to strong recent positive selection.

No Evidence for Strong Recent Positive Selection Favoring the 7 Repeat Allele of VNTR in the DRD4 Gene