Bridgett VonHoldt

Dr. Bridgett VonHoldt

orcid

Research Focus & Metrics

Academic Career Length

14Years (2013-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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7 July 2017 in Science Advances
Verified
Journal Article
Open access
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BVBridgett VonHoldt
Bridgett VonHoldt
ESEmily Shuldiner
Emily Shuldiner
IKIlana Janowitz Koch
Ilana Janowitz Koch
RKRebecca Y. Kartzinel
Rebecca Y. Kartzinel
AHAndrew Hogan
Andrew Hogan
MUMonique A. R. Udell
Monique A. R. Udell
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 of WBS 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 patients with WBS and contained within 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.

15 August 2023 in Genome Biology
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Journal Article
Open access
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JMJennifer Meadows
Jennifer Meadows
JKJeff Kidd
Jeff Kidd
GWGuo-Dong Wang
Guo-Dong Wang
HPHeidi G. Parker
Heidi G. Parker
PSPeter Z Schall
Peter Z Schall
Elaine OstranderElaine Ostrander
Elaine Ostrander
Background: The international Dog10K project aims to sequence and analyze several thousand canine genomes. Incorporating 20 × data from 1987 individuals, including 1611 dogs (321 breeds), 309 village dogs, 63 wolves, and four coyotes, we identify genomic variation across the canid family, setting the stage for detailed studies of domestication, behavior, morphology, disease susceptibility, and genome architecture and function. Results: We report the analysis of > 48 M single-nucleotide, indel, and structural variants spanning the autosomes, X chromosome, and mitochondria. We discover more than 75% of variation for 239 sampled breeds. Allele sharing analysis indicates that 94.9% of breeds form monophyletic clusters and 25 major clades. German Shepherd Dogs and related breeds show the highest allele sharing with independent breeds from multiple clades. On average, each breed dog differs from the UU_Cfam_GSD_1.0 reference at 26,960 deletions and 14,034 insertions greater than 50 bp, with wolves having 14% more variants. Discovered variants include retrogene insertions from 926 parent genes. To aid functional prioritization, single-nucleotide variants were annotated with SnpEff and Zoonomia phyloP constraint scores. Constrained positions were negatively correlated with allele frequency. Finally, the utility of the Dog10K data as an imputation reference panel is assessed, generating high-confidence calls across varied genotyping platform densities including for breeds not included in the Dog10K collection. Conclusions: We have developed a dense dataset of 1987 sequenced canids that reveals patterns of allele sharing, identifies likely functional variants, informs breed structure, and enables accurate imputation. Dog10K data are publicly available.

2 October 2019 in Proceedings Of The Royal Society B-Biological Sciences
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Journal Article
Open access
EMEvan L. MacLean
Evan L. MacLean
NSNoah Snyder-Mackler
Noah Snyder-Mackler
BVBridgett VonHoldt
Bridgett VonHoldt
JSJames A. Serpell
James A. Serpell
Variation across dog breeds presents a unique opportunity to investigate the evolution and biological basis of complex behavioural traits. We integrated behavioural data from more than 14 000 dogs from 101 breeds with breed-averaged genotypic data (n= 5697 dogs) from over 100 000 loci in the dog genome. We found high levels of among-breed heritability for 14 behavioural traits (the proportion of trait variance attributable to genetic similarity among breeds). We next identified 131 single nucleotide polymorphisms associated with breed differences in behaviour, which were found in genes that are highly expressed in the brain and enriched for neurobiological functions and developmental processes, suggesting that they may be functionally associated with behavioural differences. Our results shed light on the heritability and genetic architecture of complex behavioural traits and identify dogs as a powerful model in which to address these questions.

29 May 2017 in Conservation Letters
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Journal Article
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BVBridgett VonHoldt
Bridgett VonHoldt
KBKristin E. Brzeski
Kristin E. Brzeski
DWDavid S. Wilcove
David S. Wilcove
LRLinda Y. Rutledge
Linda Y. Rutledge
The generation of genome‐wide sequence data has brought with it both exciting opportunities for conservation and challenges for determining appropriate management practices in the face of complex evolutionary histories. Genomic data can provide deep insight into taxa with complex evolutionary origins, and is a powerful tool for biologists to obtain a more complete view of ancestry. Many policy decisions are encumbered by patterns of gene flow between species that reveal complex evolutionary histories. Here, we review conservation decisions in admixed species and highlight genomics research that demonstrates the commonality of hybridization in wildlife. We encourage a shift toward a web‐of‐life framework with emphasis on the need to incorporate flexibility in conservation practices by establishing a policy for lineages of admixed ancestry. In particular, we promote a conceptual framework under which hybridization, even extensive hybridization, no longer disqualifies a species from protection; instead, we encourage customized case‐by‐case management to protect evolutionary potential and maintain processes that sustain ecosystems.

10 April 2019 in National Science Review
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Journal Article
Open access
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Elaine OstranderElaine Ostrander
Elaine Ostrander
GWGuo-Dong Wang
Guo-Dong Wang
GLGreger Larson
Greger Larson
BVBridgett VonHoldt
Bridgett VonHoldt
BDBrian Davis
Brian Davis
WZWeiwei Zhai
Weiwei Zhai
Dogs are the most phenotypically diverse mammalian species, and they possess more known heritable disorders than any other non-human mammal. Efforts to catalog and characterize genetic variation across well-chosen populations of canines are necessary to advance our understanding of their evolutionary history and genetic architecture. To date, no organized effort has been undertaken to sequence the world's canid populations. The Dog10K Consortium (http://www.dog10kgenomes.org) is an international collaboration of researchers from across the globe who will generate 20× whole genomes from 10 000 canids in 5 years. This effort will capture the genetic diversity that underlies the phenotypic and geographical variability of modern canids worldwide. Breeds, village dogs, niche populations and extended pedigrees are currently being sequenced, and de novo assemblies of multiple canids are being constructed. This unprecedented dataset will address the genetic underpinnings of domestication, breed formation, aging, behavior and morphological variation. More generally, this effort will advance our understanding of human and canine health.

19 November 2015 in Molecular Ecology
Verified
Journal Article
Closed access
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IKIlana Janowitz Koch
Ilana Janowitz Koch
MCMichelle M. Clark
Michelle M. Clark
MTMichael J. Thompson
Michael J. Thompson
KDKerry A. Deere‐Machemer
Kerry A. Deere‐Machemer
JWJun Wang
Jun Wang
BVBridgett VonHoldt
Bridgett VonHoldt