Alternative splicing of human height-related zinc finger and BTB domain-containing 38 gene through Alu exonization

Recently, genome-wide association studies have identified a strong association between the ZBTB38 locus and human height. In a functional study, we detected two RT-PCR products of ZBTB38, amplified with primers in exons 7 and 8 from a chondrocyte cell line, C-28/I2. Sequencing revealed that the longer product contained an Alu segment in intron 7 of ZBTB38, which contained a potential splicing acceptor site that likely was used to generate the alternative transcript. Insertion of the Alu segment changed the consensus Kozak sequence of the ZBTB38 transcript, potentially altering translational efficiency. We performed RT-PCR using 16 tissue samples from humans and 8 tissue samples from primates to determine any tissue specificity or evolutionary conservation of the alternative splicing. Although we failed to identify any difference among the tissues, all primate samples expressed only the shorter Alu segment (lacking the transcript), suggesting that the alternative splicing event is hominid primate-specific.