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

Abstract

Clones containing five non-adult beta-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 beta-globin genes as well as the two adult genes to each other. Thus this entire BALB/c beta-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'-epsilon y3-beta h0-beta h1-beta h2-beta h3-beta major-beta minor-3' Portions of each of the five newly identified genes have been sequenced. Only one, epsilon y3, encodes a previously described globin. beta h0 and beta h1, which are closely related, differ significantly from both adult and embryonic globins. The beta h2 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 beta h3 gene (preceding codon 75) has an aberrant structure. The rest of this sequence is intact, resembling an adult beta-globin gene except for an inserted base at cocon 90, resulting in a frameshift. Consequently, the beta h3 sequence cannot be translated to produce a normal beta-globin.