Large-scale analysis of the Alu Ya5 and Yb8 subfamilies and their contribution to human genomic diversity

We have utilized computational biology to screen GenBank for the presence o f recently integrated Ya5 and Yb8 Alu family members. Our analysis identifi ed 2640 Ya5 Alu family members and 1852 Yb8 Alu family members from the dra ft sequence of the human genome. We selected a set of 475 of these elements for detailed analyses. Analysis of the DNA sequences from the individual A lu elements revealed a low level of random mutations within both subfamilie s consistent with the recent origin of these elements within the human geno me. Polymerase chain reaction assays were used to determine the phylogeneti c distribution and human genomic variation associated with each Alu repeat. Over 99 % of the Ya5 and Yb8 Alu family members were restricted to the hum an genome and absent from orthologous positions within the genomes of sever al non-human primates, confirming the recent origin of these Alu subfamilie s in the human genome. Approximately 1 % of the analyzed Ya5 and Yb8 Alu fa mily members had integrated into previously undefined repeated regions of t he human genome. Analysis of mosaic Yb8 elements suggests gene conversion p layed an important role in generating sequence diversity among these elemen ts. Of the 475 evaluated elements, a total of 106 of the Ya5 and Yb8 Alu fa mily members were polymorphic for insertion presence/absence within the gen omes of a diverse array of human populations. The newly identified Alu inse rtion polymorphisms will be useful tools for the study of human genomic div ersity. (C) 2001 Academic Press.