title: Mobile element scanning (ME-Scan) identifies thousands of novel Alu insertions in diverse human populations.
abstract: Alu retrotransposons are the most numerous and active mobile elements in humans, causing genetic disease and creating genomic diversity. Mobile element scanning (ME-Scan) enables comprehensive and affordable identification of mobile element insertions (MEI) using targeted high-throughput sequencing of multiplexed MEI junction libraries. In a single experiment, ME-Scan identifies nearly all AluYb8 and AluYb9 elements, with high sensitivity for both rare and common insertions, in 169 individuals of diverse ancestry. ME-Scan detects heterozygous insertions in single individuals with 91% sensitivity. Insertion presence or absence states determined by ME-Scan are 95% concordant with those determined by locus-specific PCR assays. By sampling diverse populations from Africa, South Asia, and Europe, we are able to identify 5799 Alu insertions, including 2524 novel ones, some of which occur in exons. Sub-Saharan populations and a Pygmy group in particular carry numerous intermediate-frequency Alu insertions that are absent in non-African groups. There is a significant dearth of exon-interrupting insertions among common Alu polymorphisms, but the density of singleton Alu insertions is constant across exonic and nonexonic regions. In one case, a validated novel singleton Alu interrupts a protein-coding exon of FAM187B. This implies that exonic Alu insertions are generally deleterious and thus eliminated by natural selection, but not so quickly that they cannot be observed as extremely rare variants.
authors.affiliation: Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, Utah 84112, USA. david.witherspoon@utah.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Witherspoon
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Xing
authors.forename: W Scott
authors.initials: WS
authors.lastname: Watkins
authors.forename: Hongseok
authors.initials: H
authors.lastname: Ha
authors.forename: Mark A
authors.initials: MA
authors.lastname: Batzer
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Jorde
mesh_terms: D020087:Alu Elements; D004261:DNA Replication; D005091:Exons; D056426:Genetic Loci; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D016254:Mutagenesis, Insertional; D011110:Polymorphism, Genetic; D044382:Population Groups / Q000235:genetics; D015203:Reproducibility of Results; D018626:Retroelements; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic
chemical_list: D018626:Retroelements