Alternative splicing of GATA1. (A) The sequence of the junction between exons 2 and intron 2 in 5 patients compared with wild-type sequence (first row). (B) RT-PCR analysis. M indicates marker. Lane 1: PCR-mix; lane 2: RT-mix (negative controls). Lanes 3-5: patients with splice mutations in GATA1 (patients 3, 57, and 61, respectively). Lane 6: patient 19 at diagnosis (no splice mutation); lane 7: normal bone marrow; lane 8: K562; lane 9: patient 68 (leukemia with no mutation in GATA1). The larger fragment (348 bp) corresponds to the normal splicing of exon 1 to 2 and then exon 2 to3. The smaller fragment (109 bp) corresponds to an alternative splice variant in which exon 1 is spliced to exon 3. (C) Alternative models for generation of GATA1 isoforms. The full GATA1 protein can only be translated from the full GATA1 mRNA, whereas the GATA1s protein can be translated either from the full GATA1 mRNA or from the shorter splice variant in which exon 2 is skipped.