DNA sequence organization of the β-globin complex in the BALB/c mouse

Clones containing five non-adult β-globin genes were isolated from a library of BALB/c DNA. Together, the newly cloned regions comprise a contiguous block of 32 kb of the mouse genome. Restriction mapping of genomic DNA established the physical linkage of these non-adult genes to the two adult β-globin genes as well as of the two adult genes to each other. Thus this entire BALB/c β-globin complex consists of seven linked genes, all with the same transcriptional orientation, arrayed over 70 kb of DNA. The order of these genes is:5′ϵy3βhOh1βh2βh3β_major β_minor3′ Portions of each of the five newly identified genes have been sequenced. Only one, ϵy3, encodes a previously described globin. βhO and βh1, which are closely related, differ significantly from both adult and embryonic globins. The βh2 sequence is more closely related to the adult genes than to the other non-adult genes. However, it is the sequence least homologous to both of these classes. The 5′ half of the βh3 gene (preceding codon 75) has an aberrant structure. The rest of this sequence is intact, resembling an adult β-globin gene except for an inserted base at codon 90, resulting in a frameshift. Consequently, the βh3 sequence cannot be translated to produce a normal β-globin.