Mobile elements make up nearly half of the human genome. They are a significant cause of genetic disease as a result of both de novo insertion as well as mediation of nonhomologous recombination and deletion. We propose to build on our previous research to further understand the effects of mobile elements on the generation of genetic diversity in human and non-human primate genomes. We have developed a new technique, based on second-generation high-throughput sequencing, to simultaneously ascertain and genotype all members of mobile-element subfamilies in large samples of individuals. We will apply this technology to 42 large Utah pedigrees to directly estimate, for the first time, the rate of Alu retrotransposition in the human genome. We will also use these pedigrees to explore the relationship between mobile elements and the generation of de novo copy number variants. We will genotype thousands of Alu insertion polymorphisms in a diverse sample of 500 humans. Because our new technique identifies all members of each subfamily, rare insertions will be identified so that an unbiased frequency spectrum of insertion polymorphisms can be analyzed. These data will allow us to search for active Alu elements in the human genome, and they will allow us to test several key hypotheses about ancient human evolutionary history. We will take advantage of the availability of several non-human primate genome sequences to test the effects of mobile elements on insertions and deletions of genomic material during the evolution of these species. We will also examine the roles of mobile elements in mediating transduction events in humans and non-human primates, as this is an important source of new genetic material in genomes.

Public Health Relevance

Mobile elements account for about half of our genome, and they have been shown to cause human disease by disrupting or deleting genes. We will study a large number of mobile elements to understand how they influence other elements of the genome, and we will use mobile elements to test hypotheses about the history and evolution of human populations and non-human primate species.

National Institute of Health (NIH)
Research Project (R01)
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Genetic Variation and Evolution Study Section (GVE)
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Janes, Daniel E
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University of Utah
Schools of Medicine
Salt Lake City
United States
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Carbone, Lucia; Harris, R Alan; Gnerre, Sante et al. (2014) Gibbon genome and the fast karyotype evolution of small apes. Nature 513:195-201
Marmoset Genome Sequencing and Analysis Consortium (2014) The common marmoset genome provides insight into primate biology and evolution. Nat Genet 46:850-7
Hu, Hao; Roach, Jared C; Coon, Hilary et al. (2014) A unified test of linkage analysis and rare-variant association for analysis of pedigree sequence data. Nat Biotechnol 32:663-9
Wu, Jiantao; Lee, Wan-Ping; Ward, Alistair et al. (2014) Tangram: a comprehensive toolbox for mobile element insertion detection. BMC Genomics 15:795
Chen, Karin; Wu, Wilfred; Mathew, Divij et al. (2014) Autoimmunity due to RAG deficiency and estimated disease incidence in RAG1/2 mutations. J Allergy Clin Immunol 133:880-2.e10
Li, Hong; Glusman, Gustavo; Hu, Hao et al. (2014) Relationship estimation from whole-genome sequence data. PLoS Genet 10:e1004144
Hormozdiari, Fereydoun; Konkel, Miriam K; Prado-Martinez, Javier et al. (2013) Rates and patterns of great ape retrotransposition. Proc Natl Acad Sci U S A 110:13457-62
Xing, Jinchuan; Witherspoon, David J; Jorde, Lynn B (2013) Mobile element biology: new possibilities with high-throughput sequencing. Trends Genet 29:280-9
Chen, Karin; Coonrod, Emily M; Kumanovics, Attila et al. (2013) Germline mutations in NFKB2 implicate the noncanonical NF-*B pathway in the pathogenesis of common variable immunodeficiency. Am J Hum Genet 93:812-24
Witherspoon, David J; Zhang, Yuhua; Xing, Jinchuan et al. (2013) Mobile element scanning (ME-Scan) identifies thousands of novel Alu insertions in diverse human populations. Genome Res 23:1170-81

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