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Publication : Homology of a 130-kb region enclosing the alpha-globin gene cluster, the alpha-locus controlling region, and two non-globin genes in human and mouse.

First Author  Kielman MF Year  1993
Journal  Mamm Genome Volume  4
Issue  6 Pages  314-23
PubMed ID  8318735 Mgi Jnum  J:12626
Mgi Id  MGI:60865 Doi  10.1007/BF00357090
Citation  Kielman MF, et al. (1993) Homology of a 130-kb region enclosing the alpha-globin gene cluster, the alpha-locus controlling region, and two non-globin genes in human and mouse. Mamm Genome 4(6):314-23
abstractText  The human alpha-globin gene cluster (30 kb) is embedded in a GC-rich isochore very close to the telomere of Chromosome (Chr) 16p. The alpha-Locus Controlling Region (alpha-LCR) is located upstream of the adult alpha-globin genes and has been shown to be essential for their expression. In this study we have been looking for expressed genes in the region upstream of the alpha-globin cluster to understand the role of the LCR-like element in the expression and replication timing of flanking gene clusters. We show that the upstream alpha-globin region is conserved over a 75-kb range and includes at least two oppositely transcribed non-globin genes, here referred to as Mid1 and Dist1. Complementary DNA sequences of 250 bp and 2.5 kb from Mid1 (coordinate -68) and Dist1 (coordinate -90 to -99), respectively, were isolated from human and mouse. The deduced partial amino acid sequences of these cDNAs are 81% and 95% identical for the Mid1 and Dist1 gene respectively. We have cloned a mouse cosmid contig which includes Dist1, Mid1, and the entire murine alpha-globin cluster. The murine homolog of the alpha-LCR was mapped upstream of the mouse globin genes at approximately the same position as in the human locus. Our results indicate that, in mouse and human, the alpha-globin loci and their flanking sequences are homologous over a range of at least 130 kb. The structural homology of this region in both mammals suggests also a functional one and indicates the mouse as a potential model for studying the role of the alpha-LCR controlling element in the regulation of expression and replication timing of the flanking gene clusters.
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