Activity of genes with functions in Human Williams-Beuren syndrome is impacted by mobile element insertions in the gray wolf genome
Open accessAbstract
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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BAZ1B expression is affected by domestication-related events in canids.
“(ii) the observation that its expression is affected by domestication-related events in canids (12);”
The recent observation that BAZ1B expression is affected by domestication-related mobile element insertion methylation in gray wolves further supported its role in domestication.
“The recent observation that its expression is affected by domestication-related mobile element insertion methylation in gray wolves (12) further supported its role in domestication”
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Cites
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400 · see citing works
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709 · see citing works
Cutadapt removes adapter sequences from high-throughput sequencing reads
Martin, M. (2011) · EMBnet.journal · doi:10.14806/ej.17.1.200 · Cited by 33,889 · see citing works
RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome
Li, B., & Dewey, C. N. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-323 · Cited by 22,179 · see citing works
The Human Genome Browser at UCSC
Kent, W. J., Sugnet, C. W., Furey, T. S., Roskin, K. M., Pringle, T. H., Zahler, A. M., & Haussler, A. D. (2002) · Genome Research · doi:10.1101/gr.229102 · Cited by 10,400 · see citing works
Primer3—new capabilities and interfaces
Untergasser, A., Cutcutache, I., Kõressaar, T., Ye, J., Faircloth, B., Remm, M., & Rozen, S. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks596 · Cited by 9,165 · see citing works
Enhancements and modifications of primer design program Primer3
Kõressaar, T., & Remm, M. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm091 · Cited by 2,618 · see citing works
Lin, L., Faraco, J., Li, R., Kadotani, H., Rogers, W., Lin, X., Qiu, X., de Jong, P. J., Nishino, S., & Mignot, E. (1999) · Cell · doi:10.1016/s0092-8674(00)81965-0 · Cited by 2,613 · see citing works
Rare Structural Variants Disrupt Multiple Genes in Neurodevelopmental Pathways in Schizophrenia
Walsh, T., McClellan, J. M., McCarthy, S. E., Addington, A. M., Pierce, S. B., Cooper, G. M., Nord, A. S., Kusenda, M., Malhotra, D., Bhandari, A., et al. (2008) · Science · doi:10.1126/science.1155174 · Cited by 1,800 · see citing works
Aligning Short Sequencing Reads with Bowtie
Langmead, B. (2010) · Current Protocols in Bioinformatics · doi:10.1002/0471250953.bi1107s32 · Cited by 1,270 · see citing works
Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome
Ewart, A. K., Morris, C. A., Atkinson, D., Jin, W., Sternes, K., Spallone, P., Stock, A. D., Leppert, M., & Keating, M. T. (1993) · Nature Genetics · doi:10.1038/ng0993-11 · Cited by 1,138 · see citing works
Interspersed repeats and other mementos of transposable elements in mammalian genomes
Smit, A. F. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)00031-3 · Cited by 949 · see citing works
The UCSC Genome Browser database: 2019 update
Haeussler, M., Zweig, A. S., Tyner, C., Speir, M. L., Rosenbloom, K. R., Raney, B. J., Lee, C. M., Lee, B. T., Hinrichs, A. S., Gonzalez, J. N., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky1095 · Cited by 877 · see citing works
Pober, B. R. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0903074 · Cited by 848 · see citing works
Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication
vonHoldt, B. M., Pollinger, J. P., Lohmueller, K. E., Han, E., Parker, H. G., Quignon, P., Degenhardt, J. D., Boyko, A. R., Earl, D. A., Auton, A., et al. (2010) · Nature · doi:10.1038/nature08837 · Cited by 804 · see citing works
Self-citationHollister, J. D., & Gaut, B. S. (2009) · Genome Research · doi:10.1101/gr.091678.109 · Cited by 683 · see citing works
A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs
Sutter, N. B., Bustamante, C. D., Chase, K., GRAY, M. M., Zhao, K., Zhu, L., Padhukasahasram, B., Karlins, E., Davis, S. R., Jones, P. G., et al. (2007) · Science · doi:10.1126/science.1137045 · Cited by 673 · see citing works
LIM-kinase1 Hemizygosity Implicated in Impaired Visuospatial Constructive Cognition
Frangiskakis, J. M., Ewart, A. K., Morris, C. A., Mervis, C. Β., Bertrand, J., Robinson, B. F., Klein, B. P., Ensing, G. J., Everett, L. A., Green, E. D., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)80077-x · Cited by 555 · see citing works
Luiselli, J., Happe, F. G. E., Hurst, H., et al. (2012) · Springer eBooks · doi:10.1007/978-1-4419-1698-3_101563 · Cited by 539 · see citing works
II. Hypersociability in Williams Syndrome
Jones, W., Bellugi, U., Lai, Z., Chiles, M., Reilly, J., Lincoln, A., & Adolphs, R. (2000) · Journal of Cognitive Neuroscience · doi:10.1162/089892900561968 · Cited by 503 · see citing works
Meyer-Lindenberg, A., Mervis, C. B., & Faith Berman, K. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1906 · Cited by 411 · see citing works
Parker, H. G., VonHoldt, B. M., Quignon, P., Margulies, E. H., Shao, S., Mosher, D. S., Spady, T. C., Elkahloun, A., Cargill, M., Jones, P. G., et al. (2009) · Science · doi:10.1126/science.1173275 · Cited by 342 · see citing works
Self-citationHollister, J. D., Smith, L. M., Guo, Y., Ott, F., Weigel, D., & Gaut, B. S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018222108 · Cited by 312 · see citing works
Reiter, L. T., Murakami, T., Koeuth, T., Pentao, L., Muzny, D. M., Gibbs, R. A., & Lupski, J. R. (1996) · Nature Genetics · doi:10.1038/ng0396-288 · Cited by 295 · see citing works
Tyner, C., Barber, G. P., Casper, J., Clawson, H., Diekhans, M., Eisenhart, C., Fischer, C. M., Gibson, D., Gonzalez, J. N., Guruvadoo, L., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1134 · Cited by 290 · see citing works
BS Seeker: precise mapping for bisulfite sequencing
Chen, P., Cokus, S. J., & Pellegrini, M. A. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-203 · Cited by 242 · see citing works
Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog
Clark, L. A., Wahl, J. M., Rees, C. A., & Murphy, K. E. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506940103 · Cited by 241 · see citing works
The genomic basis of the Williams – Beuren syndrome
Schubert, C. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8401-y · Cited by 236 · see citing works
The genealogy and genetic viability of reintroduced Yellowstone grey wolves
Vonholdt, B., Stahler, D., Smith, D. W., Earl, D., Pollinger, J., & Wayne, R. (2008) · Molecular Ecology · doi:10.1111/j.1365-294x.2007.03468.x · Cited by 216 · see citing works
Self-citationvonHoldt, B. M., Shuldiner, E., Koch, I. J., Kartzinel, R. Y., Hogan, A., Brubaker, L., Wanser, S., Stahler, D., Wynne, C. D. L., Ostrander, E. A., et al. (2017) · Science Advances · doi:10.1126/sciadv.1700398 · Cited by 186 · see citing works
Morris, C. A., Mervis, C. Β., Hobart, H. H., Gregg, R. G., Bertrand, J., Ensing, G. J., Sommer, A., Moore, C. A., Hopkin, R. J., Spallone, P., et al. (2003) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.20496 · Cited by 185 · see citing works
Beunders, G., Voorhoeve, E., Golzio, C., Pardo, L. M., Rosenfeld, J. A., Talkowski, M. E., Simonic, I., Lionel, A. C., Vergult, S., Pyatt, R. E., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.12.011 · Cited by 185 · see citing works
Merla, G., Howald, C., Hor, C. N., Lyle, R., Wyss, C., Zabot, M. T., Antonarakis, S. E., & Reymond, A. (2006) · The American Journal of Human Genetics · doi:10.1086/506371 · Cited by 178 · see citing works
The UCSC Genome Browser database: 2017 update.
Tyner, C., Barber, G. P., Casper, J. D., Clawson, H., Diekhans, M., Eisenhart, C., Fischer, C. M., Gibson, D., Gonzalez, J. N., Guruvadoo, L., et al. (2017) · eScholarship (California Digital Library) · Cited by 171 · see citing works
Migration‐related phenotypic divergence is associated with epigenetic modifications in rainbow trout
Baerwald, M. R., Meek, M. H., Stephens, M. R., Nagarajan, R. P., Goodbla, A. M., Tomalty, K. M. H., Thorgaard, G. H., May, B. P., & Nichols, K. M. (2015) · Molecular Ecology · doi:10.1111/mec.13231 · Cited by 162 · see citing works
A Novel Human Gene,WSTF,Is Deleted in Williams Syndrome
Lu, X., Meng, X., Morris, C. A., & Keating, M. T. (1998) · Genomics · doi:10.1006/geno.1998.5578 · Cited by 160 · see citing works
Foust, C. M., Preite, V., Schrey, A. W., Álvarez, M., Robertson, M., Verhoeven, K. J. F., & Richards, C. L. (2016) · Molecular Ecology · doi:10.1111/mec.13522 · Cited by 153 · see citing works
Pelé, M., Tiret, L., Kessler, J.-L., Blot, S., & Panthier, J. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi151 · Cited by 143 · see citing works
LIM–kinase deleted in Williams syndrome
Tassabehji, M., Metcalfe, K., Fergusson, W. D., Carette, M. J. M., Dore, J. K., Donnai, D., Read, A., Pröschel, C., Gutowski, N. J., Mao, X., et al. (1996) · Nature Genetics · doi:10.1038/ng0796-272 · Cited by 138 · see citing works
Identification of additional transcripts in the Williams-Beuren syndrome critical region
Merla, G., Ucla, C., Guipponi, M., et al. (2002) · Human Genetics · doi:10.1007/s00439-002-0710-x · Cited by 131 · see citing works
Short interspersed elements (SINEs) are a major source of canine genomic diversityPreprint
Wang, W., & Kirkness, E. F. (2005) · Genome Research · doi:10.1101/gr.3765505 · Cited by 125 · see citing works
Purification and Characterization of a New Eukaryotic Protein Translation Factor
Richter-Cook, N. J., Dever, T. E., Hensold, J. O., & Merrick, W. C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.13.7579 · Cited by 119 · see citing works
Meng, X., Lu, X., Li, Z., Green, E. D., Massa, H. F., Trask, B. J., Morris, C. A., & Keating, M. T. (1998) · Human Genetics · doi:10.1007/s004390050874 · Cited by 111 · see citing works
Duplication of GTF2I Results in Separation Anxiety in Mice and Humans
Mervis, C. Β., Dida, J., Lam, E., Crawford, N. A., Young, E. J., Henderson, D., Onay, T., Morris, C. A., Woodruff‐Borden, J., Yeomans, J. S., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.04.012 · Cited by 89 · see citing works
Koch, I. J., Clark, M. M., Thompson, M. J., Deere, K. A., Wang, J., Duarte, L., Gnanadesikan, G. E., McCoy, E. L., Rubbi, L., Stahler, D. R., et al. (2015) · Molecular Ecology · doi:10.1111/mec.13480 · Cited by 86 · see citing works
Self-citationBeunders, G., van de Kamp, J. M., Vasudevan, P. C., Morton, J., Smets, K., Kleefstra, T., de Munnik, S. A., Schuurs-Hoeijmakers, J. H. M., Ceulemans, B., Zollino, M., et al. (2016) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2015-103601 · Cited by 71 · see citing works
Cuscó, I., Corominas, R., Bayés, M., Flores, R., Rivera‐Bruguès, N., Campuzano, V., & Jurado, L. A. P. (2008) · Genome Research · doi:10.1101/gr.073197.107 · Cited by 69 · see citing works
Williams–Beuren syndrome TRIM50 encodes an E3 ubiquitin ligase
Micale, L., Fusco, C., Augello, B., Napolitano, L. M. R., Dermitzakis, E. T., Meroni, G., Merla, G., & Reymond, A. (2008) · European Journal of Human Genetics · doi:10.1038/ejhg.2008.68 · Cited by 60 · see citing works
Peoples, R., Cisco, M. J., Kaplan, P. B., & Francke, U. (1998) · Cytogenetic and Genome Research · doi:10.1159/000015110 · Cited by 56 · see citing works
Tipney, H., Hinsley, T. A., Brass, A., Metcalfe, K., Donnai, D., & Tassabehji, M. (2004) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201174 · Cited by 51 · see citing works
Nakamura, N., Toba, S., Hirai, M., et al. (2005) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.28.429 · Cited by 32 · see citing works
Pervasive Effects of Aging on Gene Expression in Wild Wolves
Charruau, P., Johnston, R. A., Stahler, D. R., Lea, A. J., Snyder‐Mackler, N., Smith, D. W., vonHoldt, B. M., Cole, S. W., Tung, J., & Wayne, R. K. (2016) · Molecular Biology and Evolution · doi:10.1093/molbev/msw072 · Cited by 30 · see citing works
Self-citationNakayama, Y., Nakamura, N., Oki, S., Wakabayashi, M., Ishihama, Y., Miyake, A., Itoh, N., & Kurosaka, A. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.370932 · Cited by 25 · see citing works
McCarron, M. Y., Duttaroy, A., Doughty, G., et al. (1994) · Genetics · doi:10.1093/genetics/136.3.1013 · Cited by 23 · see citing works
Transposon insertion resulted in the silencing of Wx-B1n in Chinese wheat landraces
Zhang, L., Chen, H., Luo, M. Y., et al. (2017) · Theoretical and Applied Genetics · doi:10.1007/s00122-017-2878-4 · Cited by 23 · see citing works
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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
- ORCID
- Venue
- Genome Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-06-01
- Volume
- 10
- Issue
- 6
- Pages
- 1546-1553
- ISSN
- 1759-6653 (ISSN-L)
- PMC
- PMC6007319
- 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
- gold
- doi.org
- Licence
- 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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