Structural variants in genes associated with human Williams-Beuren syndrome underlie stereotypical hypersociability in domestic dogs

Bridgett M. VonHoldt, Emily Shuldiner, Ilana Janowitz Koch, Rebecca Y. Kartzinel, Andrew Hogan, Lauren Brubaker, Shelby Wanser, Daniel Stahler, Clive Wynne, Elaine A. Ostrander, Janet S. Sinsheimer, Monique A.R. Udell

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Although considerable progress has been made in understanding the genetic basis of morphologic traits (for example, body size and coat color) in dogs and wolves, the genetic basis of their behavioral divergence is poorly understood. An integrative approach using both behavioral and genetic data is required to understand the molecular underpinnings of the various behavioral characteristics associated with domestication. We analyze a 5-Mb genomic region on chromosome 6 previously found to be under positive selection in domestic dog breeds. Deletion of this region in humans is linked to Williams-Beuren syndrome (WBS), a multisystem congenital disorder characterized by hypersocial behavior.We associate quantitative data on behavioral phenotypes symptomatic ofWBS in humans with structural changes in the WBS locus in dogs. We find that hypersociability, a central feature of WBS, is also a core element of domestication that distinguishes dogs from wolves. We provide evidence that structural variants in GTF2I and GTF2IRD1, genes previously implicated in the behavioral phenotype of patientswithWBS and containedwithin the WBS locus, contribute to extreme sociability in dogs. This finding suggests that there are commonalities in the genetic architecture of WBS and canine tameness and that directional selection may have targeted a unique set of linked behavioral genes of large phenotypic effect, allowing for rapid behavioral divergence of dogs and wolves, facilitating coexistence with humans.

Original languageEnglish (US)
Article numbere1700398
JournalScience advances
Volume3
Issue number7
DOIs
StatePublished - Jul 5 2017

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Williams Syndrome
Dogs
Genes
Behavioral Genetics
Phenotype
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Chromosomes, Human, Pair 6
Body Size
Canidae
Color

ASJC Scopus subject areas

  • Medicine(all)

Cite this

VonHoldt, B. M., Shuldiner, E., Koch, I. J., Kartzinel, R. Y., Hogan, A., Brubaker, L., ... Udell, M. A. R. (2017). Structural variants in genes associated with human Williams-Beuren syndrome underlie stereotypical hypersociability in domestic dogs. Science advances, 3(7), [e1700398]. https://doi.org/10.1126/sciadv.1700398

Structural variants in genes associated with human Williams-Beuren syndrome underlie stereotypical hypersociability in domestic dogs. / VonHoldt, Bridgett M.; Shuldiner, Emily; Koch, Ilana Janowitz; Kartzinel, Rebecca Y.; Hogan, Andrew; Brubaker, Lauren; Wanser, Shelby; Stahler, Daniel; Wynne, Clive; Ostrander, Elaine A.; Sinsheimer, Janet S.; Udell, Monique A.R.

In: Science advances, Vol. 3, No. 7, e1700398, 05.07.2017.

Research output: Contribution to journalArticle

VonHoldt, BM, Shuldiner, E, Koch, IJ, Kartzinel, RY, Hogan, A, Brubaker, L, Wanser, S, Stahler, D, Wynne, C, Ostrander, EA, Sinsheimer, JS & Udell, MAR 2017, 'Structural variants in genes associated with human Williams-Beuren syndrome underlie stereotypical hypersociability in domestic dogs', Science advances, vol. 3, no. 7, e1700398. https://doi.org/10.1126/sciadv.1700398
VonHoldt, Bridgett M. ; Shuldiner, Emily ; Koch, Ilana Janowitz ; Kartzinel, Rebecca Y. ; Hogan, Andrew ; Brubaker, Lauren ; Wanser, Shelby ; Stahler, Daniel ; Wynne, Clive ; Ostrander, Elaine A. ; Sinsheimer, Janet S. ; Udell, Monique A.R. / Structural variants in genes associated with human Williams-Beuren syndrome underlie stereotypical hypersociability in domestic dogs. In: Science advances. 2017 ; Vol. 3, No. 7.
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