Interspersed repetitive elements, including Alu and LINE1 (LI) elements, make up 45% of the human genome, yet much remains unknown about their origins and dynamics. There is evidence that these elements affect the distribution of genetic diversity across the genome because of their influence on processes like recombination. The goals of this project are to build upon the knowledge gained from the previous funding period in order to pursue questions about the origins of Alu and LI elements and about their effects on patterns of genomic diversity. Using a series of PCR and sequencing experiments, we will evaluate the effects of gene conversion on Alu diversity. We will assess linkage disequilibrium patterns in 50 genomic regions to test the hypothesis that Alu elements mediate homologous recombination. We will undertake comparisons of human and chimpanzee genomes to test the hypothesis that Alu elements are important mediators of unequal crossover events, deleting and duplicating genes. We predict that LI elements, because of their observed distribution and their lower density in the genome, function less frequently as mediators of unequal crossover. We have designed a series of experiments to test the hypothesis that Alu elements insert into the genome in an endonuclease-independent fashion and may therefore participate in the repair of double-stranded DNA breaks. Finally, we will apply newly developed methods to determine whether natural selection has been operating on Alu and LI elements in the human genome. Factors like gene conversion and recombination exert important effects on patterns of genomic diversity, which in turn influence patterns of linkage disequilibrium in the genome. The proposed research, which will help to explore the influence of repetitive elements on genomic diversity, will thus have important implications for the use of linkage disequilibrium in localizing disease-causing genes. Our understanding of genetic disease will also be enhanced by a better understanding of the role of these elements in DNA repair and in gene duplication and deletion.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM059290-06
Application #
7079408
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Eckstrand, Irene A
Project Start
1999-05-01
Project End
2009-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
6
Fiscal Year
2006
Total Cost
$559,754
Indirect Cost
Name
University of Utah
Department
Genetics
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Jordan, Vallmer E; Walker, Jerilyn A; Beckstrom, Thomas O et al. (2018) A computational reconstruction of Papio phylogeny using Alu insertion polymorphisms. Mob DNA 9:13
Gilbert, Clément; Feschotte, Cédric (2018) Horizontal acquisition of transposable elements and viral sequences: patterns and consequences. Curr Opin Genet Dev 49:15-24
Baker, Jasmine N; Walker, Jerilyn A; Denham, Michael W et al. (2018) Recently integratedAluinsertions in the squirrel monkey (Saimiri) lineage and application for population analyses. Mob DNA 9:9
Al-Agha, Abdulmoein Eid; Ahmed, Ihab Abdulhamed; Nuebel, Esther et al. (2018) Primary Ovarian Insufficiency and Azoospermia in Carriers of a Homozygous PSMC3IP Stop Gain Mutation. J Clin Endocrinol Metab 103:555-563
Steely, Cody J; Baker, Jasmine N; Walker, Jerilyn A et al. (2018) Analysis of lineage-specificAlusubfamilies in the genome of the olive baboon,Papio anubis. Mob DNA 9:10
Jangam, Diwash; Feschotte, Cédric; Betrán, Esther (2017) Transposable Element Domestication As an Adaptation to Evolutionary Conflicts. Trends Genet 33:817-831
Rustagi, Navin; Zhou, Anbo; Watkins, W Scott et al. (2017) Extremely low-coverage whole genome sequencing in South Asians captures population genomics information. BMC Genomics 18:396
Chuong, Edward B; Elde, Nels C; Feschotte, Cédric (2017) Regulatory activities of transposable elements: from conflicts to benefits. Nat Rev Genet 18:71-86
Gardner, Eugene J; Lam, Vincent K; Harris, Daniel N et al. (2017) The Mobile Element Locator Tool (MELT): population-scale mobile element discovery and biology. Genome Res 27:1916-1929
Walker, Jerilyn A; Jordan, Vallmer E; Steely, Cody J et al. (2017) Papio Baboon Species Indicative Alu Elements. Genome Biol Evol 9:1788-1796

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