Cited by 31Williams Syndrome ResearchChromosomal and Genetic VariationsGenomic variations and chromosomal abnormalities

Activity of genes with functions in Human Williams-Beuren syndrome is impacted by mobile element insertions in the gray wolf genome

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vonHoldt, Bridgett M, Ji, Sarah S, Aardema, Matthew L, Stahler, Daniel R, Udell, Monique A R, Sinsheimer, Janet S·2018·Genome Biology and Evolution

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.

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Authors
vonHoldt, B. M., Ji, S. S., Aardema, M. L., Stahler, D. R., Udell, M. A. R., & Sinsheimer, J. S.
Affiliations
  • Princeton University (US)
  • University of California, Los Angeles (US)
  • American Museum of Natural History (US)
  • National Park Service (US)
  • Oregon State University (US)
Corresponding author
vonHoldt, Bridgett M
Venue
Genome Biology and Evolution
Published
2018-06-01
Volume
10
Issue
6
Pages
1546-1553
ISSN
1759-6653 (ISSN-L)
OpenAlex
W2806829006
Cited by
31
References
56
Citations by year
2026: 1 · 2025: 2 · 2024: 7 · 2023: 2 · 2022: 5 · 2021: 7 · 2020: 4 · 2019: 3
FWCI
1.29
Type
journal article
Language
en
Open access
Locations
  • Genome Biology and Evolution (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
Funders
  • Gerstner Fellowship in Bioinformatics and Computational Biology to the American Museum of Natural History
  • NSF (DEB-1245373, DMS-1264153)
  • Yellowstone Forever
  • NIH (GM053275)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords
Williams syndrome, mobile element insertions, transposable elements, gray wolf, dogs, DNA methylation, epigenetic silencing, gene expression regulation, cis-regulation, copy number variation, LIMK1, GTF2I, BAZ1B, social behavior
MeSH terms
Animals, DNA Transposable Elements, Dogs, Gene Expression Regulation, Humans, Methylation, Transcription, Genetic, Gene Dosage, Williams Syndrome, Wolves, Gene Silencing, Epigenesis, Genetic, Transcriptome

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