Polymorphism and evolution of Alu sequences in the human low density lipoprotein receptor gene.

Two clusters of Alu sequences in the human low density lipoprotein (LDL) receptor gene have been analyzed in detail. One Alu cluster is present within the intron separating exons 15 and 16 of the gene and contains a polymorphic Pvu II site. The presence or absence of this site gives rise to two allelic fragments of 14 and 16.5 kilobases, respectively, in genomic Southern blots using cloned cDNA probes. This DNA polymorphic site is caused by a single adenine to guanine transition within an Alu repetitive element. The second cluster of Alu sequences is located in exon 18 of the LDL receptor gene. Southern blotting of primate DNAs suggests that this cluster became associated with the gene about 30 million years ago. Comparison of bovine DNA sequences, which lack this Alu cluster, with those of the human indicates that the Alu sequences inserted in exon 18 in two independent events.