Linkage disequilibrium and evolutionary relationships of DNA variants (restriction enzyme fragment length polymorphisms) at the serum albumin locus.

Four additional DNA variants (restriction enzyme fragment length polymorphisms) making a total of eight polymorphic sites at the human albumin locus have been identified. These eight sites were found after screening 689 of 20,000 nucleotides by using cDNA probes for albumin with 27 different restriction enzymes. One in 85 nucleotides was therefore potentially polymorphic. The average nucleotide diversity between any two randomly chosen chromosomes was calculated to be 1/500. We observed marked linkage disequilibrium between the eight variants. Only 7 haplotypes among 256 possible combinations were observed in 160 chromosomes from Caucasoids, Blacks, and Asians. Two haplotypes were found in all three human races, indicating that their origin predated human racial divergence. The three rarest haplotypes appear to represent recombinational events between the more common haplotypes. All crossovers occurred in the same general region. Studies of several nonhuman primates indicated that the origin of one haplotype predated the human-African ape divergence. Although it is not possible to rule out maintenance of this tight linkage by selection or fixation, it is suggested that the limited number of haplotypes at the chromosomal site of the albumin gene near the centromere of chromosome 4 may be the result of decreased recombination.