HUMAN-SPECIFIC ALU SEQUENCE-TAGGED SITES

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We have developed an approach to isolate the 500-1000 Alu family members that are most recently inserted in the human population. These insertions are fairly randomly arranged in the human genome, with a probable bias towards gene-containing regions. 40% of these loci are so recently inserted as to be dimorphic in the human population, with 20% of these having a high level of dimorphism. PCR probes from flanking sequences of these loci detect a striking difference in bands of either 100 bp or 400 bp, depending on whether the Alu has inserted in that individual's chromosome or not. Any individual Alu insertion is a unique event, therefore population studies can track any individual Alu insertion from that point of insertion. We find the highly dimorphic Alu family members all to be highly informative about human populations. In addition, about 20% of all of the Alu insertions have a long, simple sequence tail which tends to be very dimorphic, in a manner similar to the CA repeats. We intend to produce STSs from about 500 loci and test them for population dimorphisms, 3' end polymorphism, and preliminary chromosome mapping. Thus, producing Human-Specific Alu STSs from these (HASTS), has the potential of simultaneously promoting the programmatic goals of the Human Genome Project while also developing unique resources for molecular biological and population studies. On the one hand, by developing new sets of well tested STSs for most, or all, of the human chromosomes, the project would provide a model for how a small laboratory with an interest in a particular aspect of genome function can contribute to global physical mapping of the human genome. On the other hand, the STSs that are to be developed would be of immediate use in studying both the molecular biology and the population structure of the human. These reagents would be of major assistance to researchers studying the history of the Alu family and the current mode of Alu retroposition. They would also be of critical importance for studies of human evolution and population diversity.