Abstract 3009: Genetic and epigenetic variations resulting from Alu retrotransposition

Abstract

Abstract Alu repeats are the most prevalent retrotransposons, comprising approximately 10% of the human genome. Alu retrotransposons have amplified during primate evolution by an RNA-mediated copy and paste mechanism. Among the Alu subfamilies, AluY elements and its variants exhibit the highest rates of retrotransposition. De novo retrotransposition of active Alu elements have given rise to insertion polymorphisms in human populations. While generating methylation maps of Alu elements in human normal cerebellum and in ependymoma tumors, Xie and colleagues (2009, 2010) also identified putative new Alu element insertions. In this study, we explored these Alu libraries to identify recent Alu element insertions and to understand the (epi)genetic variations that result from such events. This study may also enable identification of DNA structural variation that may occur at the onset of tumorigenesis and/or during tumor progression. A total of 327 putative recent Alu element insertions represented by 1,762 sequence reads were identified, including 316 events that have not yet been documented in either dbSNP or dbRIP. Forty-seven out of a total of forty-nine randomly selected events representing nineteen genomic loci were sequence-verified. Alu element insertions remained heterozygous for sixteen out of nineteen genomic loci in one or more individuals. The polymorphic Alu elements are enriched for young Alu families and they present some characteristic sequence features, such as longer poly(A) tails. In addition, they also present the TT/AAAA consensus sequence at their 3’-flanking regions, and AT-rich target site duplications. Despite being homozygous or heterozygous insertions, these Alu elements are heavily methylated. Further methylation analysis on two genomic loci revealed no methylation difference in two heterozygous alleles and also no methylation difference at CpG dinucleotides flanking the Alu insertion sites. These results indicate that the recently integrated Alu elements have not influenced the methylation status of their neighboring CpG dinucleotides. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3009. doi:10.1158/1538-7445.AM2011-3009