Potential gene conversion and source genes for recently integrated Alu elements

Alu elements comprise >10% of the human genome. We have used a computationa l biology approach to analyze the human genomic DNA sequence databases to d etermine the impact of gene conversion on the sequence diversity of recentl y integrated Alu elements and to identify Alu elements that were potentiall y retroposition competent. We analyzed 269 Alu Ya5 elements and identified 23 members of a new Alu subfamily termed Ya5a2 with an estimated copy numbe r of 35 members, including the de novo Alu insertion in the NFI gene. Our a nalysis of Alu elements containing one to four (Ya1-Ya4) of the Ya5 subfami ly-specific mutations suggests that gene conversion contributed as much as 10%-20% of the variation between recently integrated Alu elements. In addit ion, analysis of the middle A-rich region of the different Alu Ya5 members indicates a tendency toward expansion of this region and subsequent generat ion of simple sequence repeats. Mining the databases for putative retroposi tion-competent elements that share 100% nucleotide identity to the previous ly reported de novo Alu insertions linked to human diseases resulted in the retrieval of 13 exact matches to the NFI Alu repeat, three to the Alu elem ent in BRCA2, and one to the Alu element in FGFR2 (Apert syndrome). Transie nt transfections of the potential source gene for the Apert's Alu with its endogenous flanking genomic sequences demonstrated the transcriptional and presumptive transpositional competency of the element.