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 α-globin gene cluster was isolated as overlapping cosmid clones and characterized. In addition to the embryonic (ζ) and adult (α) genes, the cloned contig contains the complete N-methylpurine-DNA glycosylase (MPG) gene, the α-globin-positive regulatory element (mHS-26), and a previously unidentified hypervariable region (named the mouse α-HVR). In mice, the distance between the MPG gene and mHS-26 is ∼18 kb; between the mHS-26 and the ζ-gene, ∼26 kb; from the ζ-gene to the 5′ end of the α-gene, ∼16 kb; and the two α-genes are separated by ∼12 kb. In human, the corresponding distances are ∼27 kb, ∼40 kb, ∼19 kb, and ∼3 kb respectively. The α-HVR is located ∼18 kb upstream of the mouse ζ-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 α-gene cluster. Thus, this HVR may be a valuable evolutionary marker, as well as a useful genetic marker for the mouse.