A NOVEL MOBILE ELEMENT INSERTED IN THE ALPHA-SPECTRIN GENE - SPECTRINDAYTON - A TRUNCATED ALPHA-SPECTRIN ASSOCIATED WITH HEREDITARY ELLIPTOCYTOSIS

Nonviral retrotransposons, retropseudogenes, and short interspersed nu clear elements (SINEs) are mobile DNA segments capable of transpositio n to new genomic locations, where they may alter gene expression. De n ovo integration into specific genes has been described in both germ an d somatic cells. We report a family with hereditary elliptocytosis and pyropoikilocytosis associated with a truncated alpha-spectrin protein . We present the biochemical characteristics of this abnormal protein and show that the alpha-spectrin gene is disrupted by a mobile element resulting in exon skipping. This element causes duplication of the in sertion site and is terminated by a long poly-A tail downstream of mul tiple consensus polyadenylation signals. Southern blot analysis of hum an genomic DNA, using this element as probe, reveals one to three copi es per individual. This element has no homology to any previously repo rted sequence and therefore appears to be a member of a novel family o f mobile elements.