Molecular analysis of human genetic disease and neoplasia suggests two mechanisms of genomic rearrangement involving interspersed repetitive sequences, insertional inactivation resulting from transposition, and deletion. The proposed experiments use the 2101 family of transposable repetitive sequences in seaurchins as a model system to investigate mechanisms of transposition. The experiments will attempt to answer three questions about the 2101 repeat family; are 2101 repeats linked in the genome like LTR or IVR sequences; do 2101 repeats have structural similarities to other transposable elements, including insertion site duplications and conserved transcriptional signals; and can 2101 repeat transcripts, presumably transposition intermediates, be detected in sea urchin eggs or early embryos? Additional experiments address the significance of deletion of single copy sequences flanked by repeats as an evolutionary mechanism. A variety of single copy sequences flanked by repeats will be isolated form the sea urchin and human genomes. These sequences will be used as hybridization probes on Southern and Northern blot hybridization, and DNA sequencing. Part of the work will be carried out in collaboration with Roy Britten's lab at Caltech: thus, the students will be exposed to state-of-the-art techniques and instrumentation in a highly productive research environment.
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