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Genome Biol Evol. 2018 Jun 1;10(6):1546-1553. doi: 10.1093/gbe/evy112.

Activity of Genes with Functions in Human Williams-Beuren Syndrome Is Impacted by Mobile Element Insertions in the Gray Wolf Genome.

Author information

1
Department of Ecology & Evolutionary Biology, Princeton University, New Jersey.
2
Department of Biostatistics, UCLA Fielding School of Public Health, Los Angeles, California.
3
Department of Biology, Montclair State University, New Jersey.
4
Sackler Institute for Comparative Genomics, American Museum of Natural History, New York, New York.
5
Yellowstone Center for Resources, National Park Service, Yellowstone National Park, Wyoming.
6
Department of Animal & Rangeland Sciences, Oregon State University, Oregon.
7
Departments of Human Genetics and Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, California.

Abstract

In canines, transposon dynamics have been associated with a hyper-social behavioral syndrome, although the functional mechanism has yet to be described. We investigate the epigenetic and transcriptional consequences of these behavior-associated mobile element insertions (MEIs) in dogs and Yellowstone gray wolves. We posit that the transposons themselves may not be the causative feature; rather, their transcriptional regulation may exert the functional impact. We survey four outlier transposons associated with hyper-sociability, with the expectation that they are targeted for epigenetic silencing. We predict hyper-methylation of MEIs, suggestive that the epigenetic silencing of and not the MEIs themselves may be driving dysregulation of nearby genes. We found that transposon-derived sequences are significantly hyper-methylated, regardless of their copy number or species. Further, we have assessed transcriptome sequence data and found evidence that MEIs impact the expression levels of six genes (WBSCR17, LIMK1, GTF2I, WBSCR27, BAZ1B, and BCL7B), all of which have known roles in human Williams-Beuren syndrome due to changes in copy number, typically hemizygosity. Although further evidence is needed, our results suggest that a few insertions alter local expression at multiple genes, likely through a cis-regulatory mechanism that excludes proximal methylation.

PMID:
29860323
PMCID:
PMC6007319
DOI:
10.1093/gbe/evy112
[Indexed for MEDLINE]
Free PMC Article

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