Human Genomic Deletions Mediated by Recombination between Alu Elements

• Published in: American journal of human genetics 2006-07, Vol.79 (1), p.41-53
• Main Authors: Sen, Shurjo K., Han, Kyudong, Wang, Jianxin, Lee, Jungnam, Wang, Hui, Callinan, Pauline A., Dyer, Matthew, Cordaux, Richard, Liang, Ping, Batzer, Mark A.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Gene Deletion; General aspects. Genetic counseling; Genes; Genetic disorders; Genetics; Genome, Human; Genomics; Humans; Macular Degeneration - genetics; Medical genetics; Medical sciences; Molecular Sequence Data; Monte Carlo Method; Pan troglodytes - genetics; Polymerase Chain Reaction; Recombination, Genetic; Repetitive Sequences, Nucleic Acid; Studies
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/504600

Recombination between Alu elements results in genomic deletions associated with many human genetic disorders. Here, we compare the reference human and chimpanzee genomes to determine the magnitude of this recombination process in the human lineage since the human-chimpanzee divergence ∼6 million years ago. Combining computational data mining and wet-bench experimental verification, we identified 492 human-specific deletions (for a total of ∼400 kb) attributable to this process, a significant component of the insertion/deletion spectrum of the human genome. The majority of the deletions (295 of 492) coincide with known or predicted genes (including 3 that deleted functional exons, as compared with orthologous chimpanzee genes), which implicates this process in creating a substantial portion of the genomic differences between humans and chimpanzees. Overall, we found that Alu recombination-mediated genomic deletion has had a much higher impact than was inferred from previously identified isolated events and that it continues to contribute to the dynamic nature of the human genome.