Cloning and characterization of DNA sequences surrounding the human gamma-, delta-, and beta-globin genes.

Abstract

The human -, 6-, and globin genes are located within a 30-kilobase (kb) region of DNA, of which only 20% represents the globin genes. We have attempted to define the nature of flanking and intergenic sequences by isolating recombinants containing the human e-, both y-, or the 3' end of the "globin gene from a bacteriophage library of cloned human DNA. Comparison of these recombinants and a recombinant containing the 6-and h-globin genes (HfG1) has provided the following results. The -lobin gene is located 14 kb 5' to the G7 gene. DNA sequence homology between the region containing the two G7 genes and the a an ene region is limited to only a few hundred nucleotides which include the globin coding sequences. Repetitive DNA sequences have been found in the region 3' to the globin gene. Sequences located adjacent to the -globin gene are repeated in the globin gene region. A repetitive DNA sequence more than 3.2 kb long is repeated frequently in the human genome but is not repeated in the globin gene region in the clones examined.Human hemoglobins are selectively produced in a characteristic and orderly fashion during different stages of development (1-4). During early embryogenesis, expression of the rand E genes leads to production of Hb Gower I (ref2) (5). As the primary site of erythropoiesis switches from the yolk sac to the fetal liver, production of A-and e-globins dramatically decreases.These are replaced by a-and -y-globin chain production (6). Hb Gower II (a2e2) is temporarily produced while fetal he-

Heterogeneity of DNA deletion in gamma delta beta-thalassemia.

“…The embryonic E-globin gene nonnally lies about 13 kb upstream from the Gy-globin gene (1,22). Again, the pattern of restriction sites in the region 5' to the f-globin sequences of the y8p-thalassemia chromosome does not resemble that found in cloned genomic DNA of the E-cy-intergenic region or from the immediate E-globin gene region itself (1,22,23). Therefore, this locus is also deleted from the affected chromosome.…”

Interruption of an alpha-satellite array by a short member of the KpnI family of interspersed, highly repeated monkey DNA sequences.

“…At about the same time that the KpnI and HindIll bands were discovered, Adams and coworkers described a 6.4-kbp-long stretch of repeated DNA downstream from the human Pglobin gene (1,13). These workers showed that sequences within the 6.4-kbp segment are interspersed elsewhere in the genome, and they studied the structure of several additional segments isolated from a human genomic library; the size of the homologous regions in the cloned segments varied from 3.6 to 6.4 kbp.…”

“…These structural features suggest that KpnI-RET was inserted into the satellite array as a movable element. Recent investigations have demonstrated the presence in primate genomes of a family of interspersed repeated sequences whose members are up to about 6 kilobase pairs (kbp) in length (1, 10, 13-17, 22, 24-26). The family is generally referred to as the KpnI family, although in some reports it is called the 6.4-kbp repeat unit (1,13). Estimates of the reiteration frequency of the repeat unit in humans and African green monkeys vary from about 4 x 103 to 5 x 104.…”

A cytomegalovirus DNA sequence containing tracts of tandemly repeated CA dinucleotides hybridizes to highly repetitive dispersed elements in mammalian cell genomes.

“…2). Plasmid pRK12 contains a 3.6-kb EcoRI fragment from the 3' side of human ,B-globin in pBR322 (23), and XG,B-13.5 contains a 13.5-kb fragment from further away from the 3' end of gorilla P-globin: XHyG-1 contains a 16-kb fragment from the 5' side of human _yG-globin (10).…”