GATA1 mutant proteins. (A) Direct sequence analysis of genomic DNA from sample TL4 shows a mixed signal downstream of codon 44 indicating a frame-shift mutation. Sequencing of the cloned mutated GATA1 allele demonstrates a new stop codon at position 59. (B) Bar diagram of mutant GATA1 proteins. Compared with the 414-aa wild-type GATA1, the mutant proteins in DS-TL and DS-AMKL cases contain truncations of the N-terminal activation domain (AD, shaded in dark gray). Novel peptide sequences (shaded in light gray) added to the N-terminus of truncated GATA1 are due to a shift of the reading frame. Numbers to the left of bars indicate the length of the open reading frame encoded by wild-type (414 aa) and mutant GATA1. The corresponding cases of DS-TL (coded TL) and DS-AMKL (coded A) are indicated to the right of each bar. Numbers beneath bars refer to the amino acid sequence of wild-type GATA1 and either delineate the functional domains of the wild-type protein (top bar) or the residue at which N-terminal truncation occurs in the mutant protein (dashed lines). AD indicates activation domain; Nf, N-terminal zinc finger; and Cf, C-terminal zinc finger.