Cloning and characterization of the mouse alpha globin cluster and a new hypervariable marker.

A 95-kb region of the mouse genome spanning the entire alpha-globin gene cluster was isolated as overlapping cosmid clones and characterized. In addition to the embryonic (zeta) and adult (alpha) genes, the cloned contig contains the complete N-methylpurine-DNA glycosylase (MPG) gene, the alpha-globin-positive regulatory element (mHS-26), and a previously unidentified hypervariable region (named the mouse alpha-HVR). In mice, the distance between the MPG gene and mHS-26 is approximately 18 kb; between the mHS-26 and the zeta-gene, approximately 26 kb; from the zeta-gene to the 5' end of the alpha-gene, approximately 16 kb; and the two alpha-genes are separated by approximately 12 kb. In human, the corresponding distances are approximately 27 kb, approximately 40 kb, approximately 19 kb, and approximately 3 kb respectively. The alpha-HVR is located approximately 18 kb upstream of the mouse zeta-globin gene transcription start site and contains a variable copy number tandem repeat (VNTR) array of a 35-bp sequence rich in (G+C) content. The unit sequence of the HVR shares the short core sequence with the HVRs identified in the human alpha-gene cluster. Thus, this HVR may be a valuable evolutionary marker, as well as a useful genetic marker for the mouse.