Gitanjali Elisabeth Gnanadesikan | Emory University (original) (raw)

Papers by Gitanjali Elisabeth Gnanadesikan

Research Square (Research Square), Jun 30, 2023

Williams-Beuren Syndrome (WBS) is a neurodevelopmental disorder in humans caused by a hemizygous ... more Williams-Beuren Syndrome (WBS) is a neurodevelopmental disorder in humans caused by a hemizygous deletion of 28-30 genes and characterized by hypersociability and cognitive de cits. In canines, the homologous chromosomal region shows a strong signature of selection in domestic dogs relative to gray wolves, and four structural variants derived from transposons have been associated with social behavior. To explore these genetic associations in more phenotypic detail-as well as their role in training successwe genotyped 1,001 assistance dogs from Canine Companions for Independence®, including both successful graduates and those released from the training program for behavioral problems. We collected phenotypes on each dog using puppy-raiser questionnaires, trainer questionnaires, and both cognitive and behavioral tests. Using Bayesian mixed models, we found strong associations between genotypes and certain behavioral measures, including separation-related problems, aggression when challenged or corrected, and reactivity to other dogs. Furthermore, we found moderate differences in the genotypes of dogs who graduated versus those who did not; insertions in GTF2I showed the strongest association (β = 0.23, CI 95% =-0.04, 0.49), translating to an odds-ratio of 1.25 for one insertion. Our results provide insight into the role of each of these loci in canine sociability and may inform breeding and training practices for working dog organizations. Furthermore, the observed importance of GTF2I supports the emerging consensus that GTF2I genotypes, dosage, and expression are particularly important for the social behavior phenotypes seen in WBS.

Many organisms migrate between distinct habitats, exploiting variable resources while profoundly ... more Many organisms migrate between distinct habitats, exploiting variable resources while profoundly affecting ecosystem services, disease spread, and human welfare. However, the very characteristics that make migration captivating and significant also make it difficult to study, and we lack a comprehensive understanding of which species migrate and why. Here we show that, among mammals, migration is concentrated within Cetacea and Artiodactyla but also diffusely spread throughout the class (found in 12 of 27 orders). We synthesize the many ecological drivers of round-trip migration into three types of movement—between breeding and foraging sites, between breeding and refuge sites, and continuous tracking of forage/prey—each associated with different traits (body mass, diet, locomotion, and conservation status). Our results provide only partial support for the hypothesis that migration occurs without phylogenetic constraint. Furthermore, our findings suggest that categorizing migration into these three types may aid predictions of migrants’ responses to environmental changes

bioRxiv (Cold Spring Harbor Laboratory), Mar 17, 2021

Early-emerging and highly heritable sensitivity to human communication in dogs Highlights d Dogs ... more Early-emerging and highly heritable sensitivity to human communication in dogs Highlights d Dogs exhibit social skills and interest in human faces by 8 weeks of age d Genetic factors account for nearly half of variation in dog social skills d Puppies successfully used human gestures from the very first trial Authors

Ecology and Evolution, Jun 22, 2017

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Animal Cognition, Jun 10, 2020

Trait heritability is necessary for evolution by both natural and artificial selection, yet we kn... more Trait heritability is necessary for evolution by both natural and artificial selection, yet we know little about the heritability of cognitive traits. Domestic dogs are a valuable study system for questions regarding the evolution of phenotypic diversity due to their extraordinary intraspecific variation. While previous studies have investigated morphological and behavioral variation across dog breeds, few studies have systematically assessed breed differences in cognition. We integrated data from Dognition.com—a citizen science project on dog cognition—with breed-averaged genetic data from published sources to estimate the among-breed heritability of cognitive traits using mixed models. The resulting dataset included 11 cognitive measures for 1508 adult dogs across 36 breeds. A factor analysis yielded four factors interpreted as reflecting inhibitory control, communication, memory, and physical reasoning. Narrow-sense among-breed heritability estimates—reflecting the proportion of cognitive variance attributable to additive genetic variation—revealed that scores on the inhibitory control and communication factors were highly heritable (inhibitory control: h2 = 0.70; communication: h2 = 0.39), while memory and physical reasoning were less heritable (memory: h2 = 0.17; physical reasoning: h2 = 0.21). Although the heritability of inhibitory control is partially explained by body weight, controlling for breed-average weight still yields a high heritability estimate (h2 = 0.50), while other factors are minimally affected. Our results indicate that cognitive phenotypes in dogs covary with breed relatedness and suggest that cognitive traits have strong potential to undergo selection. The highest heritabilities were observed for inhibitory control and communication, both of which are hypothesized to have been altered by domestication.

bioRxiv (Cold Spring Harbor Laboratory), Mar 4, 2022

Oxytocin has become a popular analyte in behavioral endocrinology in recent years, due in part to... more Oxytocin has become a popular analyte in behavioral endocrinology in recent years, due in part to its roles in social behavior, stress physiology, and cognition. Urine samples have the advantage of being non-invasive and minimally disruptive to collect, allowing for oxytocin measurements even in some wild populations. However, methods for urinary oxytocin immunoassay have not been sufficiently optimized and rigorously assessed for their potential limitations. Using samples from oxytocin knockout (KO) and wildtype (WT) mice, we find evidence of considerable interference in unextracted urine samples, with similar distributions of measured oxytocin in both genotypes. Importantly, although this interference can be reduced by a reversed-phase solid-phase extraction (SPE), this common approach is not sufficient for eliminating false-positive signal on three immunoassay kits. To better understand the source of the observed interference, we conducted epitope mapping of the Arbor Assays antibody and assessed its cross-reactivity with known, biologically active fragments of oxytocin. We found considerable cross-reactivity (0.5-52% by-molarity) for three fragments of oxytocin that share the core epitope, with more cross-reactivity for longer fragments. Given the presence of some cross-reactivity for even the tripeptide MIF-1, it is likely that many small protein metabolites might be sufficiently similar to the epitope that at high concentrations they interfere with immunoassays. We present a new mixed-mode cation-exchange SPE method that minimizes interference-with knockout samples measuring below the assay's limit of detection-while effectively retaining oxytocin from the urine of wildtype mice. This method demonstrates good 1 .

Psychoneuroendocrinology, Oct 1, 2021

Oxytocin has garnered much interest due to its role in affective states, social behaviors, and di... more Oxytocin has garnered much interest due to its role in affective states, social behaviors, and diverse physiological functions. However, approaches for measuring endogenous oxytocin concentrations have generated considerable controversy and debate. Common procedures for measuring oxytocin often produce uncorrelated results, and the detected concentrations frequently vary across two orders of magnitude. These findings have led some researchers to argue that immunoassays of plasma oxytocin may be unreliable and nonspecific, particularly when samples are not first processed using an extraction procedure. Here, we assess the specificity of oxytocin immunoassays using plasma samples from wildtype (WT) and oxytocin knockout (KO) mice. Plasma samples from both genotypes were measured using immunoassay and were measured with or without a solid-phase extraction. Using a commercially available kit from Arbor Assays, we demonstrate that both techniques generate a clear contrast between genotypes, with wildtype samples containing high concentrations of oxytocin (unextracted mean = 468 pg/ml; extracted mean = 381 pg/ml), while knockout samples measured below the lower limit of detection. Analytical validations demonstrated good parallelism and spike recovery for both methods. Furthermore, the same wildtype samples measured with both procedures were highly correlated (r = 0.95), although unextracted samples measured at significantly higher concentrations (p = 2.0 ×10 − 7 , Cohen's d = 2.65). To test the generalizability of these results across immunoassay kits, we performed additional assays with kits from Cayman Chemical and Enzo Life Sciences. The Cayman Chemical kit produced results similar to Arbor Assays with a clean signal differentiating WT and KO plasma, both with and without an extraction step. The Enzo kit also differentiated the genotypes, with correlation between extracted and unextracted samples, but was considerably more susceptible to interference without the extraction, as evidenced by false positive signal in KO plasma samples. The extent to which these results generalize to other species remains unknown and challenging to assess.

Integrative and Comparative Biology, Jul 29, 2020

Synopsis Given their remarkable phenotypic diversity, dogs present a unique opportunity for inves... more Synopsis Given their remarkable phenotypic diversity, dogs present a unique opportunity for investigating the genetic bases of cognitive and behavioral traits. Our previous work demonstrated that genetic relatedness among breeds accounts for a substantial portion of variation in dog cognition. Here, we investigated the genetic architecture of breed differences in cognition, seeking to identify genes that contribute to variation in cognitive phenotypes. To do so, we combined cognitive data from the citizen science project Dognition.com with published breed-average genetic polymorphism data, resulting in a dataset of 1654 individuals with cognitive phenotypes representing 49 breeds. We conducted a breedaverage genome-wide association study to identify specific polymorphisms associated with breed differences in inhibitory control, communication, memory, and physical reasoning. We found five single nucleotide polymorphisms (SNPs) that reached genome-wide significance after Bonferroni correction, located in EML1, OR52E2, HS3ST5, a U6 spliceosomal RNA, and a long noncoding RNA. When we combined results across multiple SNPs within the same gene, we identified 188 genes implicated in breed differences in cognition. This gene set included more genes than expected by chance that were (1) differentially expressed in brain tissue and (2) involved in nervous system functions including peripheral nervous system development, Wnt signaling, presynapse assembly, and synaptic vesicle exocytosis. These results advance our understanding of the genetic underpinnings of complex cognitive phenotypes and identify specific genetic variants for further research.

Animal Cognition, 2020

While our understanding of adult dog cognition has grown considerably over the past 20 years, rel... more While our understanding of adult dog cognition has grown considerably over the past 20 years, relatively little is known about the ontogeny of dog cognition. To assess the development and longitudinal stability of cognitive traits in dogs, we administered a battery of tasks to 160 candidate assistance dogs at 2 timepoints. The tasks were designed to measure diverse aspects of cognition, ranging from executive function (e.g., inhibitory control, reversal learning, memory) to sensory discrimination (e.g., vision, audition, olfaction) to social interaction with humans. Subjects first participated as 8-10-week-old puppies, and then were retested on the same tasks at ~ 21 months of age. With few exceptions, task performance improved with age, with the largest effects observed for measures of executive function and social gaze. Results also indicated that individual differences were both early emerging and enduring; for example, social attention to humans, use of human communicative signals, independent persistence at a problem, odor discrimination, and inhibitory control all exhibited moderate levels of rank-order stability between the two timepoints. Using multiple regression, we found that young adult performance on many cognitive tasks could be predicted from a set of cognitive measures collected in early development. Our findings contribute to knowledge about changes in dog cognition across early development as well as the origins and developmental stability of individual differences.

Current Biology, 2021

Dogs exhibit similarities to humans in their sensitivity to cooperative-communicative cues, but t... more Dogs exhibit similarities to humans in their sensitivity to cooperative-communicative cues, but the extent to which they are biologically prepared for communication with humans is heavily debated. To investigate the developmental and genetic origins of these traits, we tested 375 eight-week-old dog puppies on a battery of social-cognitive measures. We hypothesized that if dogs' social skills for cooperating with humans are biologically prepared, then these skills should emerge robustly in early development, not require extensive socialization or learning, and exhibit heritable variation. Puppies were highly skillful at using diverse human gestures and we found no evidence of learning across test trials, suggesting that they possess these skills prior to their first exposure to these cues. Critically, over 40% of the variation in dogs' point-following abilities and attention to human faces was attributable to genetic factors. Our results suggest that these social skills in dogs emerge early in development and are under strong genetic control.

To promote collaboration across canine science, address reproducibility issues, and advance open ... more To promote collaboration across canine science, address reproducibility issues, and advance open science practices within animal cognition, we have launched the ManyDogs consortium, modeled on similar ManyX projects in other fields. We aimed to create a collaborative network that (a) uses large, diverse samples to investigate and replicate findings, (b) promotes open science practices of preregistering hypotheses, methods, and analysis plans, (c) investigates the influence of differences across populations and breeds, and (d) examines how different research methods and testing environments influence the robustness of results. Our first study combines a phenomenon that appears to be highly robust—dogs’ ability to follow human pointing—with a question that remains controversial: do dogs interpret pointing as a social communicative gesture or as a simple associative cue? We collected preliminary data (N = 61) from a single laboratory on two conditions of a 2-alternative object choice t...

Current Biology, 2021

Highlights d Dog puppies are more attracted to humans than wolf puppies raised by humans d Dog pu... more Highlights d Dog puppies are more attracted to humans than wolf puppies raised by humans d Dog puppies use human gestures and make eye contact more than wolf puppies d Both species perform similarly on memory and inhibitory control tasks d Dogs' early emerging social skills demonstrate domestication's effect on cognition

Animal Behaviour, 2020

To characterize the early ontogeny of dog cognition, we tested 168 domestic dog, Canis familiaris... more To characterize the early ontogeny of dog cognition, we tested 168 domestic dog, Canis familiaris, puppies (97 females, 71 males; mean age ¼ 9.2 weeks) in a novel test battery based on previous tasks developed and employed with adolescent and adult dogs. Our sample consisted of Labrador retrievers, golden retrievers and Labrador  golden retriever crosses from 65 different litters at Canine Companions for Independence, an organization that breeds, trains and places assistance dogs for people with disabilities. Puppies participated in a 3-day cognitive battery that consisted of 14 tasks measuring different cognitive abilities and temperament traits such as executive function (e.g. inhibitory control, reversal learning, working memory), use of social cues, sensory discriminations and reactivity to and recovery from novel situations. At 8e10 weeks of age, and despite minimal experience with humans, puppies reliably used a variety of cooperative-communicative gestures from humans. Puppies accurately remembered the location of hidden food for delays of up to 20 s, and succeeded in a variety of visual, olfactory and auditory discrimination problems. They also showed some skill at executive function tasks requiring inhibitory control and reversal learning, although they scored lower on these tasks than is typical in adulthood. Taken together, our results confirm the early emergence of sensitivity to human communication in dogs and contextualize these skills within a broad array of other cognitive abilities measured at the same stage of ontogeny.

Dogs have a special place in human history as the first domesticated species and play important r... more Dogs have a special place in human history as the first domesticated species and play important roles in many cultures around the world. However, their role in scientific studies has been relatively recent. With a few notable exceptions (e.g., Darwin, Pavlov, Scott, and Fuller), domestic dogs were not commonly the subject of rigorous scientific investigation of behavior until the late 1990s. While the number of canine science studies has increased dramatically over the last 20 years, most research groups are limited in the inferences they can draw due to the relatively small sample sizes used, along with the exceptional diversity observed in dogs (e.g., breed, geographic location, experience). To this end, we introduce the ManyDogs Project, an international consortium of researchers interested in taking a big team science approach to understanding canine behavioral science. We begin by discussing why studying dogs provides valuable insights into behavior and cognition, evolutionary ...

Molecular Ecology, 2015

The process of domestication can exert intense trait-targeted selection on genes and regulatory r... more The process of domestication can exert intense trait-targeted selection on genes and regulatory regions. Specifically, rapid shifts in the structure and sequence of genomic regulatory elements could provide an explanation for the extensive, and sometimes extreme, variation in phenotypic traits observed in domesticated species. Here, we explored methylation differences from >24 000 cytosines distributed across the genomes of the domesticated dog (Canis familiaris) and the grey wolf (Canis lupus). PCA and model-based cluster analyses identified two primary groups, domestic vs. wild canids. A scan for significantly differentially methylated sites (DMSs) revealed species-specific patterns at 68 sites after correcting for cell heterogeneity, with weak yet significant hypermethylation typical of purebred dogs when compared to wolves (59% and 58%, P < 0.05, respectively). Additionally, methylation patterns at eight genes significantly deviated from neutrality, with similar trends of hypermethylation in purebred dogs. The majority (>66%) of differentially methylated regions contained or were associated with repetitive elements, indicative of a genotype-mediated trend. However, DMSs were also often linked to functionally relevant genes (e.g. neurotransmitters). Finally, we utilized known genealogical relationships among Yellowstone wolves to survey transmission stability of methylation marks, from which we found a substantial fraction that demonstrated high heritability (both H(2) and h(2 )…

Research Square (Research Square), Jun 30, 2023

Williams-Beuren Syndrome (WBS) is a neurodevelopmental disorder in humans caused by a hemizygous ... more Williams-Beuren Syndrome (WBS) is a neurodevelopmental disorder in humans caused by a hemizygous deletion of 28-30 genes and characterized by hypersociability and cognitive de cits. In canines, the homologous chromosomal region shows a strong signature of selection in domestic dogs relative to gray wolves, and four structural variants derived from transposons have been associated with social behavior. To explore these genetic associations in more phenotypic detail-as well as their role in training successwe genotyped 1,001 assistance dogs from Canine Companions for Independence®, including both successful graduates and those released from the training program for behavioral problems. We collected phenotypes on each dog using puppy-raiser questionnaires, trainer questionnaires, and both cognitive and behavioral tests. Using Bayesian mixed models, we found strong associations between genotypes and certain behavioral measures, including separation-related problems, aggression when challenged or corrected, and reactivity to other dogs. Furthermore, we found moderate differences in the genotypes of dogs who graduated versus those who did not; insertions in GTF2I showed the strongest association (β = 0.23, CI 95% =-0.04, 0.49), translating to an odds-ratio of 1.25 for one insertion. Our results provide insight into the role of each of these loci in canine sociability and may inform breeding and training practices for working dog organizations. Furthermore, the observed importance of GTF2I supports the emerging consensus that GTF2I genotypes, dosage, and expression are particularly important for the social behavior phenotypes seen in WBS.

Many organisms migrate between distinct habitats, exploiting variable resources while profoundly ... more Many organisms migrate between distinct habitats, exploiting variable resources while profoundly affecting ecosystem services, disease spread, and human welfare. However, the very characteristics that make migration captivating and significant also make it difficult to study, and we lack a comprehensive understanding of which species migrate and why. Here we show that, among mammals, migration is concentrated within Cetacea and Artiodactyla but also diffusely spread throughout the class (found in 12 of 27 orders). We synthesize the many ecological drivers of round-trip migration into three types of movement—between breeding and foraging sites, between breeding and refuge sites, and continuous tracking of forage/prey—each associated with different traits (body mass, diet, locomotion, and conservation status). Our results provide only partial support for the hypothesis that migration occurs without phylogenetic constraint. Furthermore, our findings suggest that categorizing migration into these three types may aid predictions of migrants’ responses to environmental changes

bioRxiv (Cold Spring Harbor Laboratory), Mar 17, 2021

Early-emerging and highly heritable sensitivity to human communication in dogs Highlights d Dogs ... more Early-emerging and highly heritable sensitivity to human communication in dogs Highlights d Dogs exhibit social skills and interest in human faces by 8 weeks of age d Genetic factors account for nearly half of variation in dog social skills d Puppies successfully used human gestures from the very first trial Authors

Ecology and Evolution, Jun 22, 2017

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Animal Cognition, Jun 10, 2020

Trait heritability is necessary for evolution by both natural and artificial selection, yet we kn... more Trait heritability is necessary for evolution by both natural and artificial selection, yet we know little about the heritability of cognitive traits. Domestic dogs are a valuable study system for questions regarding the evolution of phenotypic diversity due to their extraordinary intraspecific variation. While previous studies have investigated morphological and behavioral variation across dog breeds, few studies have systematically assessed breed differences in cognition. We integrated data from Dognition.com—a citizen science project on dog cognition—with breed-averaged genetic data from published sources to estimate the among-breed heritability of cognitive traits using mixed models. The resulting dataset included 11 cognitive measures for 1508 adult dogs across 36 breeds. A factor analysis yielded four factors interpreted as reflecting inhibitory control, communication, memory, and physical reasoning. Narrow-sense among-breed heritability estimates—reflecting the proportion of cognitive variance attributable to additive genetic variation—revealed that scores on the inhibitory control and communication factors were highly heritable (inhibitory control: h2 = 0.70; communication: h2 = 0.39), while memory and physical reasoning were less heritable (memory: h2 = 0.17; physical reasoning: h2 = 0.21). Although the heritability of inhibitory control is partially explained by body weight, controlling for breed-average weight still yields a high heritability estimate (h2 = 0.50), while other factors are minimally affected. Our results indicate that cognitive phenotypes in dogs covary with breed relatedness and suggest that cognitive traits have strong potential to undergo selection. The highest heritabilities were observed for inhibitory control and communication, both of which are hypothesized to have been altered by domestication.

bioRxiv (Cold Spring Harbor Laboratory), Mar 4, 2022

Oxytocin has become a popular analyte in behavioral endocrinology in recent years, due in part to... more Oxytocin has become a popular analyte in behavioral endocrinology in recent years, due in part to its roles in social behavior, stress physiology, and cognition. Urine samples have the advantage of being non-invasive and minimally disruptive to collect, allowing for oxytocin measurements even in some wild populations. However, methods for urinary oxytocin immunoassay have not been sufficiently optimized and rigorously assessed for their potential limitations. Using samples from oxytocin knockout (KO) and wildtype (WT) mice, we find evidence of considerable interference in unextracted urine samples, with similar distributions of measured oxytocin in both genotypes. Importantly, although this interference can be reduced by a reversed-phase solid-phase extraction (SPE), this common approach is not sufficient for eliminating false-positive signal on three immunoassay kits. To better understand the source of the observed interference, we conducted epitope mapping of the Arbor Assays antibody and assessed its cross-reactivity with known, biologically active fragments of oxytocin. We found considerable cross-reactivity (0.5-52% by-molarity) for three fragments of oxytocin that share the core epitope, with more cross-reactivity for longer fragments. Given the presence of some cross-reactivity for even the tripeptide MIF-1, it is likely that many small protein metabolites might be sufficiently similar to the epitope that at high concentrations they interfere with immunoassays. We present a new mixed-mode cation-exchange SPE method that minimizes interference-with knockout samples measuring below the assay's limit of detection-while effectively retaining oxytocin from the urine of wildtype mice. This method demonstrates good 1 .

Psychoneuroendocrinology, Oct 1, 2021

Oxytocin has garnered much interest due to its role in affective states, social behaviors, and di... more Oxytocin has garnered much interest due to its role in affective states, social behaviors, and diverse physiological functions. However, approaches for measuring endogenous oxytocin concentrations have generated considerable controversy and debate. Common procedures for measuring oxytocin often produce uncorrelated results, and the detected concentrations frequently vary across two orders of magnitude. These findings have led some researchers to argue that immunoassays of plasma oxytocin may be unreliable and nonspecific, particularly when samples are not first processed using an extraction procedure. Here, we assess the specificity of oxytocin immunoassays using plasma samples from wildtype (WT) and oxytocin knockout (KO) mice. Plasma samples from both genotypes were measured using immunoassay and were measured with or without a solid-phase extraction. Using a commercially available kit from Arbor Assays, we demonstrate that both techniques generate a clear contrast between genotypes, with wildtype samples containing high concentrations of oxytocin (unextracted mean = 468 pg/ml; extracted mean = 381 pg/ml), while knockout samples measured below the lower limit of detection. Analytical validations demonstrated good parallelism and spike recovery for both methods. Furthermore, the same wildtype samples measured with both procedures were highly correlated (r = 0.95), although unextracted samples measured at significantly higher concentrations (p = 2.0 ×10 − 7 , Cohen's d = 2.65). To test the generalizability of these results across immunoassay kits, we performed additional assays with kits from Cayman Chemical and Enzo Life Sciences. The Cayman Chemical kit produced results similar to Arbor Assays with a clean signal differentiating WT and KO plasma, both with and without an extraction step. The Enzo kit also differentiated the genotypes, with correlation between extracted and unextracted samples, but was considerably more susceptible to interference without the extraction, as evidenced by false positive signal in KO plasma samples. The extent to which these results generalize to other species remains unknown and challenging to assess.

Integrative and Comparative Biology, Jul 29, 2020

Synopsis Given their remarkable phenotypic diversity, dogs present a unique opportunity for inves... more Synopsis Given their remarkable phenotypic diversity, dogs present a unique opportunity for investigating the genetic bases of cognitive and behavioral traits. Our previous work demonstrated that genetic relatedness among breeds accounts for a substantial portion of variation in dog cognition. Here, we investigated the genetic architecture of breed differences in cognition, seeking to identify genes that contribute to variation in cognitive phenotypes. To do so, we combined cognitive data from the citizen science project Dognition.com with published breed-average genetic polymorphism data, resulting in a dataset of 1654 individuals with cognitive phenotypes representing 49 breeds. We conducted a breedaverage genome-wide association study to identify specific polymorphisms associated with breed differences in inhibitory control, communication, memory, and physical reasoning. We found five single nucleotide polymorphisms (SNPs) that reached genome-wide significance after Bonferroni correction, located in EML1, OR52E2, HS3ST5, a U6 spliceosomal RNA, and a long noncoding RNA. When we combined results across multiple SNPs within the same gene, we identified 188 genes implicated in breed differences in cognition. This gene set included more genes than expected by chance that were (1) differentially expressed in brain tissue and (2) involved in nervous system functions including peripheral nervous system development, Wnt signaling, presynapse assembly, and synaptic vesicle exocytosis. These results advance our understanding of the genetic underpinnings of complex cognitive phenotypes and identify specific genetic variants for further research.

Animal Cognition, 2020

While our understanding of adult dog cognition has grown considerably over the past 20 years, rel... more While our understanding of adult dog cognition has grown considerably over the past 20 years, relatively little is known about the ontogeny of dog cognition. To assess the development and longitudinal stability of cognitive traits in dogs, we administered a battery of tasks to 160 candidate assistance dogs at 2 timepoints. The tasks were designed to measure diverse aspects of cognition, ranging from executive function (e.g., inhibitory control, reversal learning, memory) to sensory discrimination (e.g., vision, audition, olfaction) to social interaction with humans. Subjects first participated as 8-10-week-old puppies, and then were retested on the same tasks at ~ 21 months of age. With few exceptions, task performance improved with age, with the largest effects observed for measures of executive function and social gaze. Results also indicated that individual differences were both early emerging and enduring; for example, social attention to humans, use of human communicative signals, independent persistence at a problem, odor discrimination, and inhibitory control all exhibited moderate levels of rank-order stability between the two timepoints. Using multiple regression, we found that young adult performance on many cognitive tasks could be predicted from a set of cognitive measures collected in early development. Our findings contribute to knowledge about changes in dog cognition across early development as well as the origins and developmental stability of individual differences.

Current Biology, 2021

Dogs exhibit similarities to humans in their sensitivity to cooperative-communicative cues, but t... more Dogs exhibit similarities to humans in their sensitivity to cooperative-communicative cues, but the extent to which they are biologically prepared for communication with humans is heavily debated. To investigate the developmental and genetic origins of these traits, we tested 375 eight-week-old dog puppies on a battery of social-cognitive measures. We hypothesized that if dogs' social skills for cooperating with humans are biologically prepared, then these skills should emerge robustly in early development, not require extensive socialization or learning, and exhibit heritable variation. Puppies were highly skillful at using diverse human gestures and we found no evidence of learning across test trials, suggesting that they possess these skills prior to their first exposure to these cues. Critically, over 40% of the variation in dogs' point-following abilities and attention to human faces was attributable to genetic factors. Our results suggest that these social skills in dogs emerge early in development and are under strong genetic control.

To promote collaboration across canine science, address reproducibility issues, and advance open ... more To promote collaboration across canine science, address reproducibility issues, and advance open science practices within animal cognition, we have launched the ManyDogs consortium, modeled on similar ManyX projects in other fields. We aimed to create a collaborative network that (a) uses large, diverse samples to investigate and replicate findings, (b) promotes open science practices of preregistering hypotheses, methods, and analysis plans, (c) investigates the influence of differences across populations and breeds, and (d) examines how different research methods and testing environments influence the robustness of results. Our first study combines a phenomenon that appears to be highly robust—dogs’ ability to follow human pointing—with a question that remains controversial: do dogs interpret pointing as a social communicative gesture or as a simple associative cue? We collected preliminary data (N = 61) from a single laboratory on two conditions of a 2-alternative object choice t...

Current Biology, 2021

Highlights d Dog puppies are more attracted to humans than wolf puppies raised by humans d Dog pu... more Highlights d Dog puppies are more attracted to humans than wolf puppies raised by humans d Dog puppies use human gestures and make eye contact more than wolf puppies d Both species perform similarly on memory and inhibitory control tasks d Dogs' early emerging social skills demonstrate domestication's effect on cognition

Animal Behaviour, 2020

To characterize the early ontogeny of dog cognition, we tested 168 domestic dog, Canis familiaris... more To characterize the early ontogeny of dog cognition, we tested 168 domestic dog, Canis familiaris, puppies (97 females, 71 males; mean age ¼ 9.2 weeks) in a novel test battery based on previous tasks developed and employed with adolescent and adult dogs. Our sample consisted of Labrador retrievers, golden retrievers and Labrador  golden retriever crosses from 65 different litters at Canine Companions for Independence, an organization that breeds, trains and places assistance dogs for people with disabilities. Puppies participated in a 3-day cognitive battery that consisted of 14 tasks measuring different cognitive abilities and temperament traits such as executive function (e.g. inhibitory control, reversal learning, working memory), use of social cues, sensory discriminations and reactivity to and recovery from novel situations. At 8e10 weeks of age, and despite minimal experience with humans, puppies reliably used a variety of cooperative-communicative gestures from humans. Puppies accurately remembered the location of hidden food for delays of up to 20 s, and succeeded in a variety of visual, olfactory and auditory discrimination problems. They also showed some skill at executive function tasks requiring inhibitory control and reversal learning, although they scored lower on these tasks than is typical in adulthood. Taken together, our results confirm the early emergence of sensitivity to human communication in dogs and contextualize these skills within a broad array of other cognitive abilities measured at the same stage of ontogeny.

Dogs have a special place in human history as the first domesticated species and play important r... more Dogs have a special place in human history as the first domesticated species and play important roles in many cultures around the world. However, their role in scientific studies has been relatively recent. With a few notable exceptions (e.g., Darwin, Pavlov, Scott, and Fuller), domestic dogs were not commonly the subject of rigorous scientific investigation of behavior until the late 1990s. While the number of canine science studies has increased dramatically over the last 20 years, most research groups are limited in the inferences they can draw due to the relatively small sample sizes used, along with the exceptional diversity observed in dogs (e.g., breed, geographic location, experience). To this end, we introduce the ManyDogs Project, an international consortium of researchers interested in taking a big team science approach to understanding canine behavioral science. We begin by discussing why studying dogs provides valuable insights into behavior and cognition, evolutionary ...

Molecular Ecology, 2015

The process of domestication can exert intense trait-targeted selection on genes and regulatory r... more The process of domestication can exert intense trait-targeted selection on genes and regulatory regions. Specifically, rapid shifts in the structure and sequence of genomic regulatory elements could provide an explanation for the extensive, and sometimes extreme, variation in phenotypic traits observed in domesticated species. Here, we explored methylation differences from >24 000 cytosines distributed across the genomes of the domesticated dog (Canis familiaris) and the grey wolf (Canis lupus). PCA and model-based cluster analyses identified two primary groups, domestic vs. wild canids. A scan for significantly differentially methylated sites (DMSs) revealed species-specific patterns at 68 sites after correcting for cell heterogeneity, with weak yet significant hypermethylation typical of purebred dogs when compared to wolves (59% and 58%, P < 0.05, respectively). Additionally, methylation patterns at eight genes significantly deviated from neutrality, with similar trends of hypermethylation in purebred dogs. The majority (>66%) of differentially methylated regions contained or were associated with repetitive elements, indicative of a genotype-mediated trend. However, DMSs were also often linked to functionally relevant genes (e.g. neurotransmitters). Finally, we utilized known genealogical relationships among Yellowstone wolves to survey transmission stability of methylation marks, from which we found a substantial fraction that demonstrated high heritability (both H(2) and h(2 )…