“Genetic Prevalence and Clinical Relevance of Canine Mendelian Disease Variants in over One Million Dogs”, Donner et al 2022

“Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs”⁠, Jonas Donner, Jamie Freyer, Stephen Davison, Heidi Anderson, Matthew Blades, Leena Honkanen, Laura Inman et al (2022-06-14; heritability / rare-variants; similar):

[Donner et al 2018] Hundreds of genetic variants linked to Mendelian disease have been characterized in dogs to date, and commercial screening is being offered for most of them worldwide. There typically remains a paucity of information regarding the broader population frequency of newly discovered variants, as well as uncertainty regarding their functional and clinical impact on additional genomic ancestry backgrounds beyond the discovery breed. Panel screening of disease variants, commercially offered as direct-to-consumer genetic testing, provides an opportunity to establish large-scale cohorts with both genotype and phenotype data available to address open questions related to variant prevalence and relevance

. In this study, we screened the largest canine cohort examined in a single study to date (1,054,293 representative dogs from our existing cohort of more than three million dogs; a total of 811,628 mixed breed dogs and 242,665 purebreds from more than 150 countries and territories) for 250 genetic disease-associated variants to understand their prevalence and distribution in the general population. Electronic medical records from veterinary clinics were available for 43.5% of the genotyped dogs, enabling follow up on the clinical impact of variants.

We provide detailed frequencies for all tested variants across breeds and find that 57% of dogs carry at least one copy of a studied Mendelian disease-linked variant. We provide evidence of full penetrance for 10 variants, and at minimum plausible evidence for the clinical-significance of 22 variants, on a wide variety of breed backgrounds. We further show that a reduction in genome-wide heterozygosity is associated with an increased Mendelian disease load and assess genome-wide heterozygosity levels in over 100 breeds.

The accumulated knowledge represents a resource to guide discussions on disease variant presence and genetic test relevance by breed.

“DNA Methylation Clocks for Dogs and Humans”, Horvath et al 2022

“DNA methylation clocks for dogs and humans”⁠, Steve Horvath, Ake T. Lu, Amin Haghani, Joseph A. Zoller, Caesar Z. Li, Andrea R. Lim, Robert T. Brooke et al (2022-05-17; genetics / sequencing⁠, longevity / epigenetics; similar):

Epigenetic estimators of age (known as “clocks”) allow one to identify interventions that slow or reverse aging. Previous epigenetic clocks only applied to one species at a time.

Here, we describe epigenetic clocks that apply to both dogs and humans.

These clocks, which measure methylation levels in highly conserved stretches of the DNA, promise to increase the likelihood that interventions that reverse epigenetic age in one species will have the same effect in the other.

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DNA methylation profiles have been used to develop biomarkers of aging known as epigenetic clocks, which predict chronological age with remarkable accuracy and show promise for inferring health status as an indicator of biological age. Epigenetic clocks were first built to monitor human aging, but their underlying principles appear to be evolutionarily conserved⁠, as they have now been successfully developed for many mammalian species.

Here, we describe reliable and highly accurate epigenetic clocks shown to apply to 93 domestic dog breeds. The methylation profiles were generated using the mammalian methylation array, which utilizes DNA sequences that are conserved across all mammalian species. Canine epigenetic clocks were constructed to estimate age and also average time to death.

We also present 2 highly accurate human-dog dual species epigenetic clocks (r = 0.97), which may facilitate the ready translation from canine to human use (or vice versa) of antiaging treatments being developed for longevity and preventive medicine. Finally, epigenome-wide association studies here reveal individual methylation sites that may underlie the inverse relationship between breed weight and lifespan.

Overall, we describe robust biomarkers to measure aging and, potentially, health status in canines.

See Also:

• Epigenetic clocks: A review

• An open science study of ageing in companion dogs

• DNA methylation age of human tissues and cell types

• Ultra-cheap and scalable epigenetic age predictions with TIME-Seq

• Clock Work: Deconstructing the Epigenetic Clock Signals in Aging, Disease, and Reprogramming

• Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test

• Current perspectives on the cellular and molecular features of epigenetic ageing

• TRIIM: Reversal of epigenetic aging and immunosenescent trends in humans

• Reversal of Epigenetic Age with Diet and Lifestyle in a Pilot Randomized Clinical Trial

“Predicting Dog Phenotypes from Genotypes”, Bartusiak et al 2022

“Predicting Dog Phenotypes from Genotypes”⁠, Emily R. Bartusiak, Míriam Barrabés, Aigerim Rymbekova, Julia Gimbernat-Mayol, Cayetana López, Lorenzo Barberis et al (2022-04-14; similar):

We analyze dog genotypes (ie. positions of dog DNA sequences that often vary between different dogs) in order to predict the corresponding phenotypes (ie., unique observed characteristics). More specifically, given chromosome data from a dog, we aim to predict the breed, height, and weight. We explore a variety of linear and non-linear classification and regression techniques to accomplish these three tasks. We also investigate the use of a neural network (both in linear and non-linear modes) for breed classification and compare the performance to traditional statistical methods. We show that linear methods generally outperform or match the performance of non-linear methods for breed classification. However, we show that the reverse is true for height and weight regression. Finally, we evaluate the results of all of these methods based on the number of input features used in the analysis. We conduct experiments using different fractions of the full genomic sequences, resulting in input sequences ranging from 20 SNPs to ~200k SNPs. In doing so, we explore the impact of using a very limited number of SNPs for prediction. Our experiments demonstrate that these phenotypes in dogs can be predicted with as few as 0.5% of randomly selected SNPs (ie. 992 SNPs) and that dog breeds can be classified with 50% balanced accuracy with as few as 0.02% SNPs (ie. 40 SNPs).

“An Open Science Study of Ageing in Companion Dogs”, Creevy et al 2022

2022-creevy.pdf: “An open science study of ageing in companion dogs”⁠, Kate E. Creevy, Joshua M. Akey, Matt Kaeberlein, Daniel E. L. Promislow, Brian G. Barnett, Brooke Benton et al (2022-02-02; longevity / epigenetics; similar):

The Dog Aging Project (DAP) is a long-term longitudinal study of ageing in tens of thousands [>30k] of companion dogs.

The domestic dog is among the most variable mammal species in terms of morphology, behaviour, risk of age-related disease and life expectancy. Given that dogs share the human environment and have a sophisticated healthcare system but are much shorter-lived than people, they offer an unique opportunity to identify the genetic, environmental and lifestyle factors associated with healthy lifespan.

To take advantage of this opportunity, the Dog Aging Project will collect extensive survey data, environmental information, electronic veterinary medical records, genome-wide sequence information, clinicopathology and molecular phenotypes derived from blood cells, plasma and faecal samples.

Here, we describe the specific goals and design of the Dog Aging Project and discuss the potential for this open-data, community science study to greatly enhance understanding of ageing in a genetically variable, socially relevant species living in a complex environment.

1. Objectives—science of ageing

   • Define normative ageing in dogs as a function of breed, size and sex
   • Identify genetic and environmental determinants of age-specific morbidity and mortality in companion dogs
   • Develop panels of prognostic and predictive biomarkers
   • Increase the duration of healthy lifespan in dogs

2. Objectives—open science

   • Create an open-data resource for comprehensive study of the genetic and environmental determinants of healthy ageing in companion dogs
   • Provide researchers with access to biospecimens through the DAP Biobank⁠, together with the detailed longitudinal data associated with each biospecimen
   • Build and maintain a research infrastructure that allows for addition of new studies within the DAP framework
   • Study and promote ethical approaches for research in companion animals

…The DAP has 4 primary scientific aims. These include (1) characterizing ageing in companion dogs on 3 separate axes: multimorbidity, frailty and inflammaging; (2) using low-coverage whole-genome sequencing with imputation on at least 10,000 dogs to analyse the genetic architecture of age-related traits in dogs; (3) collecting metabolome, epigenome and microbiome profiles to develop biomarkers of ageing in dogs [epigenetic clock] and to better understand the mechanisms by which genetic, environmental and lifestyle variation influence ageing; and (4) carrying out a randomized, double-masked, placebo-controlled study to determine the effects of rapamycin on lifespan and healthspan in large-breed, middle-aged dogs.

See Also:

• “Frequency and distribution of 152 genetic disease variants in over 100,000 mixed breed and purebred dogs”

• “Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice”

• “Genetic testing of dogs predicts problem behaviors in clinical and nonclinical samples”

• “Once-daily feeding is associated with better cognitive function and health in companion dogs: Results from the Dog Aging Project”

• “The effect of inbreeding, body size and morphology on health in dog breeds”

• “Complex feline disease mapping using a dense genotyping array”

“The Effect of Inbreeding, Body Size and Morphology on Health in Dog Breeds”, Bannasch et al 2021

“The effect of inbreeding, body size and morphology on health in dog breeds”⁠, Danika Bannasch, Thomas Famula, Jonas Donner, Heidi Anderson, Leena Honkanen, Kevin Batcher, Noa Safra et al (2021-12-02; heritability / rare-variants⁠, genetics / selection / artificial; similar):

Background: Dog breeds are known for their distinctive body shape, size, coat color, head type and behaviors, features that are relatively similar across members of a breed. Unfortunately, dog breeds are also characterized by distinct predispositions to disease. We explored the relationships between inbreeding⁠, morphology and health using genotype based inbreeding estimates, body weight and insurance data for morbidity.

Results: A large dataset (227 breeds; dataset 1) of median heterozygosity values (H) was obtained through commercial DNA testing of 49,378 dogs…In order to investigate the effect of inbreeding level on health we utilized breed-based health data from Agria pet insurance…The average inbreeding based on genotype across 227 breeds was F_adj = 0.249 (95% CI 0.235–0.263).

There were statistically-significant differences in morbidity between breeds with low and high inbreeding (H = 16.49, p = 0.0004). There was also a statistically-significant difference in morbidity between brachycephalic breeds and non-brachycephalic breeds (p = 0.0048) and between functionally distinct groups of breeds (H = 14.95 p < 0.0001). Morbidity was modeled using robust regression analysis and both body weight (p < 0.0001) and inbreeding (p = 0.013) were statistically-significant (R² = 0.77).

Smaller less inbred breeds were healthier than larger more inbred breeds.

Conclusions: In this study, body size and inbreeding along with deleterious morphologies contributed to increases in necessary health care in dogs.

…The inbreeding values within dog breeds were very high, with the mean being 0.24, just below the coefficient of inbreeding obtained from breeding full siblings. The breeds with low inbreeding included recent cross breeds (Tamaskan Dog, Barbet and Australian Labradoodle) and landrace breeds (Danish-Swedish Farmdog, Mudi and Koolie), supporting the notion that high inbreeding is a result of closed stud books or small numbers of founders or both. It also demonstrates that it is possible to have consistent breed type without inbreeding.

Similar to another recent study, brachycephalic dogs require more veterinary care than non-brachycephalic dogs.³⁴ In addition, we identified that FCI group 2 breeds required the highest average number of veterinary care events. This group includes the larger molossoid dog breeds which others have previously identified as having higher mortality^32, 44. The primitive FCI group 5 breeds had the lowest average morbidity of all the groups, which has not been reported previously, except for the Norrbottenspitz breed.⁴⁵ This may be, in part, due to the large number of primitive breeds for which there is insurance data available in our data set, while other studies may not have had health data available for these breeds.

There were interesting exceptions to the correlation of inbreeding and health. The Border terrier, Basenji, Collie, and English setter breeds have high inbreeding but low morbidity. Likewise, the Malinois, Pomeranian and Russian Tsvetnaya Bolonka (Russian Toy) have lower inbreeding and high morbidity. These example breeds are neither brachycephalic nor particularly known for extreme morphologies. In the case of healthy breeds with high inbreeding, it may be possible that these breeds have been purged of deleterious alleles as has happened with inbred mouse strains [Mouse genetics concepts and applications, Silver 1995]. In the opposite situation (lower inbreeding and high morbidity), the recorded morbidities could be high allele frequency Mendelian diseases or potentially conditions linked to phenotypes under selection in the breed. These discrepancies could also exist due to population differences between the insurance data and the inbreeding data.

…One must consider that the majority of dog breeds displayed high levels of inbreeding well above what would be considered safe for either humans or wild animal populations. The effects of inbreeding on overall fitness have been demonstrated experimentally using mice, where an overall reduction in fitness between mice with F = 0.25 compared to F = 0 was determined to be 57%.⁵⁴ While this high level of inbreeding was less relevant to many captive and wild species, it is highly relevant to purebred dogs, based on the average inbreeding identified in this study. However the rate of inbreeding between these mouse experiments and what has occurred in dogs breeds is not the same and could have an effect on health. In humans, modest levels of inbreeding (3–6%) were shown to be associated with increased prevalence of late onset complex diseases ⁵⁵ as well as other types of inbreeding depression⁠.¹¹ These findings in other species combined with the incredibly strong breed predispositions to complex diseases like cancers and autoimmune diseases highlight the potential relevance of high inbreeding in dogs to their health.

“Epigenetic Predictors of Maximum Lifespan and Other Life History Traits in Mammals”, Li et al 2021

“Epigenetic predictors of maximum lifespan and other life history traits in mammals”⁠, C. Z. Li, A. Haghani, T. R. Robeck, D. Villar, A. T. Lu, J. Zhang, C. G. Faulkes, H. Vu, J. Ablaeva, D. M. Adams et al (2021-05-18; longevity / epigenetics; similar):

[commentary] Maximum lifespan of a species is the oldest that individuals can survive, reflecting the genetic limit of longevity in an ideal environment.

Here we report methylation-based models that accurately predict maximum lifespan (r = 0.89), gestational time (r = 0.96), and age at sexual maturity (r = 0.87), using cytosine methylation patterns collected from over 12,000 samples derived from 192 mammalian species.

Our epigenetic maximum lifespan predictor corroborated the extended lifespan in growth hormone receptor knockout mice and rapamycin treated mice. Across dog breeds, epigenetic maximum lifespan correlates positively with breed lifespan but negatively with breed size. Lifespan-related cytosines are located in transcriptional regulatory regions, such as bivalent chromatin promoters and polycomb-repressed regions, which were hypomethylated in long-lived species.

The epigenetic estimators of maximum lifespan and other life history traits will be useful for characterizing understudied species and for identifying interventions that extend lifespan.

“Genome-scale Sequencing and Analysis of Human, Wolf and Bison DNA from 25,000 Year-old Sediment”, Gelabert et al 2021

“Genome-scale sequencing and analysis of human, wolf and bison DNA from 25,000 year-old sediment”⁠, Pere Gelabert, Susanna Sawyer, Anders Bergström, Thomas C. Collin, Tengiz Meshveliani, Anna Belfer-Cohen et al (2021-01-08; genetics / selection / natural / human⁠, genetics / sequencing; backlinks; similar):

Archaeological sediments have been shown to preserve ancient DNA, but so far have not yielded genome-scale information of the magnitude of skeletal remains. We retrieved and analysed human and mammalian low-coverage nuclear and high-coverage mitochondrial genomes from Upper Palaeolithic sediments from Satsurblia cave, western Georgia, dated to 25,000 years ago. First, a human female genome with substantial basal Eurasian ancestry, which was an ancestry component of the majority of post-Ice Age people in the Near East, North Africa, and parts of Europe. Second, a wolf genome that is basal to extant Eurasian wolves and dogs and represents a previously unknown, likely extinct, Caucasian lineage that diverged from the ancestors of modern wolves and dogs before these diversified. Third, a bison genome that is basal to present-day populations, suggesting that population structure has been substantially reshaped since the Last Glacial Maximum. Our results provide new insights into the late Pleistocene genetic histories of these three species, and demonstrate that sediment DNA can be used not only for species identification, but also be a source of genome-wide ancestry information and genetic history.

Highlights: We demonstrate for the first time that genome sequencing from sediments is comparable to that of skeletal remains

A single Pleistocene sediment sample from the Caucasus yielded three low-coverage mammalian ancient genomes

We show that sediment ancient DNA can reveal important aspects of the human and faunal past

Evidence of an uncharacterized human lineage from the Caucasus before the Last Glacial Maximum

~0.01× coverage wolf and bison genomes are both basal to present-day diversity, suggesting reshaping of population structure in both species

“Genome Scans of Dog Behavior Implicate a Gene Network Underlying Psychopathology in Mammals, including Humans”, Zapata et al 2021

“Genome scans of dog behavior implicate a gene network underlying psychopathology in mammals, including humans”⁠, Isain Zapata, Erin E. Hecht, James A. Serpell, Carlos E. Alvarez (2021; psychiatry; similar):

Genetic studies show a general factor associated with all human psychopathology and strongly correlated with personality and intelligence, but its basis is unknown. We performed genome scans of 17 normal and problem behaviors in three multi-breed dog cohorts. 21 of 90 mapped loci were supported for the same, or a related, trait in a second cohort. Several of those loci were also associated with brain structure differences across breeds; and six of the respective top-candidate genes are also associated with human brain structure and function. More broadly, the geneset of canine behavioral scans is supported by enrichment for genes mapped for human behavior, personality, cognition, psychopathology and brain structure. The biology implicated includes, neurogenesis, axon guidance, angiogenesis, brain structure, alternative splicing, disease association, Hox-family transcription factors, and subiculum expression. Because body size and behavior are correlated in dogs, we isolated the effect of body size in the dog mapping and in the comparative human UK Biobank analyses. Our dog findings are consistent with pleiotropy of diverse brain traits with energy metabolism and growth, and suggest behavioral variations often affect neurogenesis. There is support for such pleiotropy in humans and well-powered genetic studies of human psychiatric traits consistently implicate neurogenesis. We propose a genetic network which underlies neuron birth and development throughout life is associated with evolutionary adaptation of behavior and the general psychopathology factor. This understanding has implications for genetic and environmental contributions to psychiatric disease. We discuss how canine translational models can further accelerate the study of psychopathology.

Author summary

We genetically mapped diverse normal and problem behaviors in dogs. The well-established approach we used is ideally suited for finding variation that is common across dog breeds and for pin-pointing the most likely gene candidates. Our analysis of the genes implicated at 90 genome regions shows they are enriched for (8) genes mapped for diverse brain functions and pathologies in humans; (2) genes involved in brain development throughout life; and (3) footprints of evolution in dogs, humans and other animals. We propose that is consistent with evolutionary conservation of the general genetic factor of mental health in humans, which is correlated with personality and intelligence. The implications are that this super-network of genes is preferentially targeted by evolutionary adaptation for behavior and that its dysregulation increases risk of mental health disorders.

“Dogs' (Canis Lupus Familiaris) Behavioral Adaptations to a Human-dominated Niche: A Review and Novel Hypothesis”, Wynne 2021

2021-wynne.pdf: “Dogs' (Canis lupus familiaris) behavioral adaptations to a human-dominated niche: A review and novel hypothesis”⁠, Clive D.L. Wynne (2021; dog⁠, genetics / selection / artificial; similar):

This chapter contextualizes the dog-human relationship in the dog’s origin as a scavenger on the fringes of human settlements over 15,000 years ago. It then reviews the evidence for unique evolved cognitive structures in dogs that could explain their success in a human-dominated world.

Failing to find evidence of unique human-like social-cognitive capacities I then review uncontroversial facts of dogs’ basic behavioral biology, including reproductive and foraging behavior and, particularly, affiliative and attachment-related behaviors. This leads to consideration of dogs’ social behavior, both conspecific and toward other species, especially humans.

I draw attention to a seldom-noted apparent contradiction between dogs’ stronger affectional bonds toward humans than toward members of their own species. Dogs’ social groups also show steeper social hierarchies accompanied by more behaviors indicating formal dominance than do other canid species including wolves.

I resolve this contradiction by proposing that dogs’ intense sensitivity to social hierarchy contributes to their willingness to accept human leadership. People commonly control resources that dogs need and also unknowingly express behaviors which dogs perceive as formal signs of dominance. This may be what Darwin was referring to when he endorsed the idea that a dog looks on his master as on a god.

Whatever the merits of this idea, if it serves to redirect behavioral research on dogs in human society more toward the social interactions of these species in their diverse forms of symbiosis it will have served an useful function.

[Keywords: domestication, symbiosis, imprinting, dominance, social hierarchy, dogs (Canis lupus familiaris), wolves (Canis lupus lupus)]

1. The origins of dogs

2. Adaptation to a human-dominated niche

   1. Cognitive hypotheses
   2. Social ecology and behavioral development of dogs
   3. Social relationships

3. Theories of dog social uniqueness

   1. Theories of increased “friendliness” and decreased aggression
   2. “Relaxed selection” theory
   3. Canine cooperation hypothesis
   4. Social ecology hypothesis
   5. A novel hypothesis: Super-dominance

4. Open questions

   1. Publication trends
   2. Imprinting and formation of social bonds
   3. What makes people want to care for dogs?
   4. What do people and dogs do together?
   5. Can we identify social hierarchy in dog-human groups?
   6. What are the intra-species social connections of dogs like?
   7. Social genetics

5. Conclusions

6. Acknowledgments

7. References

“Genetic Testing of Dogs Predicts Problem Behaviors in Clinical and Nonclinical Samples”, Zapata et al 2020

“Genetic testing of dogs predicts problem behaviors in clinical and nonclinical samples”⁠, Isain Zapata, M. Leanne Lilly, Meghan E. Herron, James A. Serpell, Carlos E. Alvarez (2020-08-14; similar):

Very little is known about the etiology of personality and psychiatric disorders. Because the core neurobiology of many such traits is evolutionarily conserved, dogs present a powerful model. We previously reported genome scans of breed averages of ten traits related to fear, anxiety, aggression and social behavior in multiple cohorts of pedigree dogs. As a second phase of that discovery, here we tested the ability of markers at 13 of those loci to predict canine behavior in a community sample of 397 pedigree and mixed-breed dogs with individual-level genotype and phenotype data. We found support for all markers and loci. By including 122 dogs with veterinary behavioral diagnoses in our cohort, we were able to identify eight loci associated with those diagnoses. Logistic regression models showed subsets of those loci could predict behavioral diagnoses. We corroborated our previous findings that small body size is associated with many problem behaviors and large body size is associated with increased trainability. Children in the home were associated with anxiety traits; illness and other animals in the home with coprophagia; working-dog status with increased energy and separation-related problems; and competitive dogs with increased aggression directed at familiar dogs, but reduced fear directed at humans and unfamiliar dogs. Compared to other dogs, Pit Bull-type dogs were not defined by a set of our markers and were not more aggressive; but they were strongly associated with pulling on the leash. Using severity-threshold models, Pit Bull-type dogs showed reduced risk of owner-directed aggression (75^th quantile) and increased risk of dog-directed fear (95^th quantile). Our findings have broad utility, including for clinical and breeding purposes, but we caution that thorough understanding is necessary for their interpretation and use.

“Significant Neuroanatomical Variation among Domestic Dog Breeds”, Hecht et al 2019

2019-hecht.pdf: “Significant neuroanatomical variation among domestic dog breeds”⁠, Erin E. Hecht, Jeroen B. Smaers, William J. Dunn, Marc Kent, Todd M. Preuss, David A. Gutman (2019-09-02; dog⁠, genetics / selection / artificial⁠, neuroscience)

“Throwing the Baby Out With the Bath Water: Could Widespread Neutering of Companion Dogs Cause Problems at a Population Level?”, Dawson et al 2019

“Throwing the Baby Out With the Bath Water: Could Widespread Neutering of Companion Dogs Cause Problems at a Population Level?”⁠, Jessica K. Dawson, Tiffani J. Howell, Matthew B. Ruby, Pauleen C. Bennett (2019-07-22; cat genetics⁠, dysgenics; backlinks; similar):

In many countries where companion dogs are popular, owners are strongly encouraged to neuter their dogs. Consequently, millions of dogs are neutered each year. In recent times considerable attention has been paid to the possible effects of such procedures on canine health and welfare. Less scrutinized are the potential ramifications of widespread neutering on the breeding of dogs and their continued success as human companions. This paper summarizes research investigating factors influencing the breeding and rearing of dogs most suited to companionship roles in contemporary, typically high-density, communities, and briefly reviews current breeder practices. It then argues that a fundamental shift to promote inclusion of “proven” companion dogs in the gene pool, as opposed to dogs meeting conformation or working/​sporting standards, is required to successfully meet the needs of modern urban dog owners. A new model is proposed, whereby responsible owners and breeders work together to produce dogs most suited for life as human companions.

…The demonstrated importance of genetics and early environment in determining behavioral predispositions makes it imperative to consider where companion dogs come from. Prior to the widespread introduction of neutering practices, dogs often bred indiscriminately, and people typically obtained their dogs for free from neighbors whose bitch had produced a litter (47). While this was problematic in terms of creating dog overpopulation, it meant that most of the dogs who produced offspring were well suited to the demands of the lives they were expected to lead. Those who weren’t well-suited were disposed of. Today, strong demand for companion dogs, coupled with rapid urbanization, increased concern regarding the welfare of animals, particularly companion dogs, and high neutering rates, has resulted in a multimillion-dollar industry involving the selective breeding and selling of puppies (48). Widespread neutering means that humans intentionally control nearly all dog breeding in developed countries…As described previously, in many developed countries, neutering companion dogs is considered an important aspect of responsible ownership. Hence, the very best companion dogs in the general community, those owned by responsible citizens who choose their dogs carefully and ensure they are reared correctly, are almost certainly those most likely to be neutered. Conversely, it is those companion dog owners who fail to perform the “responsible” behavior of neutering their dog who are perhaps most likely to breed. These “breeders” may also choose not to perform other “responsible” behaviors, such as selecting their dog carefully, testing it for genetic disorders, or evaluating the dog’s suitability as a companion prior to allowing it to reproduce. In other words, they may not thoroughly consider the genetic and environmental factors known to be critical to optimal puppy development.

Second, we advocate that all dogs should be independently tested for suitability before being bred—much as breeders now advertise that their puppies’ parents are successful show dogs, or that they are free from known genetic disorders, so they should be encouraged to advertise that independent testing has shown their breeding dogs to be well-suited behaviourally to life as human companions. We anticipate that responsible breeders would be willing to pay for this independent certification, much as they presently pay for genetic tests, eye screening and tests for hip dysplasia. Several behavioral tests exist to measure specific traits, such as the Socially Acceptable Behavior test (64), which measures aggression, or the Dog Mentality Assessment test (65), which examines levels of playfulness, curiosity, aggression, sociability, and chase-proneness. In the USA, the Canine Good Citizen program, administered by the American Kennel Club, takes <30 min to administer and is designed to identify dogs that meet ten objectives consistent with being a good companion dog. Any one of these tests could be used as a basis for developing an assessment suited to breeding dogs—dogs that are not themselves good companions are less likely to produce puppies able to excel at this role.

“Evidence of Large Genetic Influences on Dog Ownership in the Swedish Twin Registry Has Implications for Understanding Domestication and Health Associations”, Fall et al 2019

“Evidence of large genetic influences on dog ownership in the Swedish Twin Registry has implications for understanding domestication and health associations”⁠, Tove Fall, Ralf Kuja-Halkola, Keith Dobney, Carri Westgarth, Patrik K. E. Magnusson (2019-05-16; backlinks; similar):

Dogs were the first domesticated animal and, according to the archaeological evidence, have had a close relationship with humans for at least 15,000 years. Today, dogs are common pets in our society and have been linked to increased well-being and improved health outcomes in their owners. A dog in the family during childhood is associated with ownership in adult life. The underlying factors behind this association could be related to experiences or to genetic influences.

We aimed to investigate the heritability of dog ownership in a large twin sample including all twins in the Swedish Twin Registry born between 1926 and 1996 and alive in 2006. Information about dog ownership was available from 2001 to 2016 from national dog registers. The final data set included 85,542 twins from 50,507 twin pairs with known zygosity, where information on both twins were available in 35,035 pairs. Structural equation modeling was performed to estimate additive genetic effects (the heritability), common/​shared environmental, and unique/​non-shared environmental effects.

We found that additive genetic factors largely contributed to dog ownership, with heritability estimated at 57% for females and 51% for males. An effect of shared environmental factors was only observed in early adulthood. In conclusion, we show a strong genetic contribution to dog ownership in adulthood in a large twin study. We see two main implications of this finding: (1) genetic variation may have contributed to our ability to domesticate dogs and other animals and (2) potential pleiotropic effects of genetic variation affecting dog ownership should be considered in studies examining health impacts of dog ownership.

“Absolute Brain Size Predicts Dog Breed Differences in Executive Function”, Horschler et al 2019

2019-horschler.pdf: “Absolute brain size predicts dog breed differences in executive function”⁠, Daniel J. Horschler, Brian Hare, Josep Call, Juliane Kaminski, Ádám Miklósi, Evan L. MacLean (2019-01-03; dog⁠, genetics / selection / artificial⁠, IQ; backlinks; similar):

Large-scale phylogenetic studies of animal cognition have revealed robust links between absolute brain volume and species differences in executive function. However, past comparative samples have been composed largely of primates, which are characterized by evolutionarily derived neural scaling rules. Therefore, it is currently unknown whether positive associations between brain volume and executive function reflect a broad-scale evolutionary phenomenon, or alternatively, an unique consequence of primate brain evolution.

Domestic dogs provide a powerful opportunity for investigating this question due to their close genetic relatedness, but vast intraspecific variation. Using citizen science data on more than 7000 purebred dogs from 74 breeds, and controlling for genetic relatedness between breeds, we identify strong relationships between estimated absolute brain weight and breed differences in cognition. Specifically, larger-brained breeds performed statistically-significantly better on measures of short-term memory and self-control. However, the relationships between estimated brain weight and other cognitive measures varied widely, supporting domain-specific accounts of cognitive evolution.

Our results suggest that evolutionary increases in brain size are positively associated with taxonomic differences in executive function, even in the absence of primate-like neuroanatomy. These findings also suggest that variation between dog breeds may present a powerful model for investigating correlated changes in neuroanatomy and cognition among closely related taxa.

“Highly Heritable and Functionally Relevant Breed Differences in Dog Behavior”, MacLeant et al 2019

“Highly Heritable and Functionally Relevant Breed Differences in Dog Behavior”⁠, Evan L. MacLeant, Noah Snyder-Mackler, Bridgett M. vonHoldt, James A. Serpell (2019; backlinks; similar):

Variation across dog breeds presents an unique opportunity for investigating the evolution and biological basis of complex behavioral traits. We integrated behavioral data from more than 17,000 dogs from 101 breeds with breed-averaged genotypic data (n = 5,697 dogs) from over 100,000 loci in the dog genome. Across 14 traits, we found that breed differences in behavior are highly heritable, and that clustering of breeds based on behavior accurately recapitulates genetic relationships. We identify 131 single nucleotide polymorphisms associated with breed differences in behavior, which are found in genes that are highly expressed in the brain and enriched for neurobiological functions and developmental processes. Our results provide insight into the heritability and genetic architecture of complex behavioral traits, and suggest that dogs provide a powerful model for these questions.

“Dog Cloning For Special Forces: Breed All You Can Breed”, Branwen 2018

Clone: “Dog Cloning For Special Forces: Breed All You Can Breed”⁠, Gwern Branwen (2018-09-18; R⁠, dog⁠, cloning⁠, genetics / selection / artificial⁠, statistics / decision⁠, order statistics; backlinks; similar):

Decision analysis of whether cloning the most elite Special Forces dogs is a profitable improvement over standard selection procedures. Unless training is extremely cheap or heritability is extremely low, dog cloning is hypothetically profitable.

Cloning is widely used in animal & plant breeding despite steep costs due to its advantages; more unusual recent applications include creating entire polo horse teams and reported trials of cloning in elite police/​Special Forces war dogs. Given the cost of dog cloning, however, can this ever make more sense than standard screening methods for selecting from working dog breeds, or would the increase in successful dog training be too low under all reasonable models to turn a profit?

I model the question as one of expected cost per dog with the trait of successfully passing training, success in training being a dichotomous liability threshold with a polygenic genetic architecture; given the extreme level of selection possible in selecting the best among already-elite Special Forces dogs and a range of heritabilities, this predicts clones’ success probabilities. To approximate the relevant parameters, I look at some reported training costs and success rates for regular dog candidates, broad dog heritabilities, and the few current dog cloning case studies reported in the media.

Since none of the relevant parameters are known with confidence, I run the cost-benefit equation for many hypothetical scenarios, and find that in a large fraction of them covering most plausible values, dog cloning would improve training yields enough to be profitable (in addition to its other advantages).

As further illustration of the use-case of screening for an extreme outcome based on a partial predictor, I consider the question of whether height PGSes could be used to screen the US population for people of NBA height, which turns out to be reasonably doable with current & future PGSes.

• Benefits
• Modeling the SF selection problem
  • South Korea
  • Cost-benefit in selection problems
• Base Rates
  • Dog Success Rates
  • Clone Success Rates
• Heritability
• Costs
  • Training
  • Cloning
• Liability threshold model
  • Cost-benefit
    • Scenarios
• Conclusion
• See Also
• Appendix
  • Dog heritabilities
  • NBA Screening Scenario
    • Genomic Prediction of Height
    • Height in NBA Basketball
    • Height as Screening Problem
    • Model
    • Scenarios

“Direct-to-consumer DNA Testing of 6,000 Dogs Reveals 98.6-kb Duplication Associated With Blue Eyes and Heterochromia in Siberian Huskies”, Deane-Coe et al 2018

“Direct-to-consumer DNA testing of 6,000 dogs reveals 98.6-kb duplication associated with blue eyes and heterochromia in Siberian Huskies”⁠, Petra E. Deane-Coe, Erin T. Chu, Andrea Slavney, Adam R. Boyko, Aaron J. Sams (2018-08-20; backlinks; similar):

Consumer genomics enables genetic discovery on an unprecedented scale by linking very large databases of personal genomic data with phenotype information voluntarily submitted via web-based surveys. These databases are having a transformative effect on human genomics research, yielding insights on increasingly complex traits, behaviors, and disease by including many thousands of individuals in genome-wide association studies (GWAS). The promise of consumer genomic data is not limited to human research, however. Genomic tools for dogs are readily available, with hundreds of causal Mendelian variants already characterized, because selection and breeding have led to dramatic phenotypic diversity underlain by a simple genetic structure. Here, we report the results of the first consumer genomics study ever conducted in a non-human model: a GWAS of blue eyes based on more than 3,000 customer dogs with validation panels including nearly 3,000 more, the largest canine GWAS to date. We discovered a novel association with blue eyes on chromosome 18 (p = 1.3×10⁻⁶⁸) and used both sequence coverage and microarray probe intensity data to identify the putative causal variant: a 98.6-kb duplication directly upstream of the Homeobox gene ALX4, which plays an important role in mammalian eye development. This duplication is largely restricted to Siberian Huskies, is strongly associated with the blue-eyed phenotype (chi-square p = 5.2×10⁻²⁹⁰), and is highly, but not completely, penetrant. These results underscore the power of consumer-data-driven discovery in non-human species, especially dogs, where there is intense owner interest in the personal genomic information of their pets, a high level of engagement with web-based surveys, and an underlying genetic architecture ideal for mapping studies.

Author summary: The genetic underpinnings of many phenotypic traits in domestic dogs remain undiscovered. Although two genetic loci are known to underlie blue eye color in dogs, these do not explain all cases of blue eyes. By examining > 3,000 dogs from the Embark Veterinary, Inc. customer database, representing the first genome-wide association study (GWAS) driven by consumer genomics in dogs and the largest dog GWAS cohort to-date, we have shown that a region of canine chromosome 18 carrying a tandem duplication near the ALX4 gene is strongly associated with blue eye color variation, primarily in Siberian Huskies. We also provide evidence that this duplication is associated with blue eye color in non-merle Australian Shepherds. While beyond the scope of this work, future studies of the functional mechanism underlying this association may lead to discovery of a novel pathway by which blue-eyes develop in mammals. These results highlight the power and promise of consumer-data-driven discovery in non-human species.

“Canine Transmissible Venereal Tumor Genome Reveals Ancient Introgression from Coyotes to Arctic Sled Dogs”, Wang et al 2018

“Canine transmissible venereal tumor genome reveals ancient introgression from coyotes to arctic sled dogs”⁠, Xuan Wang, Bo-Wen Zhou, Ting-Ting Yin, Fang-Liang Chen, Ali Esmailizadeh, Melissa M. Turner, Andrei D. Poyarkov et al (2018-06-19; dog cloning; similar):

Canine transmissible venereal tumor (CTVT), the oldest known somatic cell line, is a living fossil, originating from cancer cells transmitted from a host to other canids during the mating process. Clonal origin analyses hints that the original dog infected with CTVT (CTVT founder) came from an ancient sled dog or wolf population. However, the genetic composition of the CTVT founder is still not clear.

In order to explore this issue, we applied whole genome sequencing (WGS) to two CTVT samples, their corresponding hosts, and 24 additional canids (Supplementary Note). Combined with published WGS data of two CTVT samples and high quality canine WGS data, we constructed a data set containing WGS data of four CTVT samples a 169-individual reference panel composed of worldwide gray wolves (Canis lupus), dogs (Canis lupus familiaris), coyotes (Canis latrans) and golden jackals (Canis aureus) (Supplementary Note, Table S1).

…Our results reveal that the CTVT founder was more closely related to present-day arctic sled dogs than to any other populations (Figure S6–8), in accordance with very recent results. However, ADMIXTURE analysis showed that the CTVT founder also possessed an ancestral component found predominantly in non-dog populations, a result that we do not observe for any arctic sled dog (Supplementary Note, Figure 1A). Moreover, the CTVT founder did not cluster tightly with arctic sled dogs in the PCA analysis (Figure S7). These results imply that the CTVT founder belonged to a previously unknown arctic dog population that is not represented in the reference panel…

In conclusion, our detailed analyses reveal that the CTVT founder came from an arctic sled dog population that possessed introgression from a population related to coyotes, a result that was not known in previous studies. Considering the habitat of coyotes in North America, we propose two hypotheses: (1) The CTVT founder lived in the arctic region of North America. (2) The CTVT founder lived in the arctic region of the Far East, where arctic dogs possessing the introgressed segments migrated through the Bering Strait in an unknown period. Hence, an ancient story of canine admixture is hidden in the genome of a living fossil, the CTVT. To further test our hypotheses of ancient admixture and to better understand the detailed evolutionary history of dogs from the arctic region and Americas, it is crucial to acquire ancient samples in these regions in future work.

“Frequency and Distribution of 152 Genetic Disease Variants in over 100,000 Mixed Breed and Purebred Dogs”, Donner et al 2018

“Frequency and distribution of 152 genetic disease variants in over 100,000 mixed breed and purebred dogs”⁠, Jonas Donner, Heidi Anderson, Stephen Davison, Angela M. Hughes, Julia Bouirmane, Johan Lindqvist, Katherine M. Lytle et al (2018-04-11; heritability / rare-variants; backlinks; similar):

Knowledge on the genetic epidemiology of disorders in the dog population has implications for both veterinary medicine and sustainable breeding. Limited data on frequencies of genetic disease variants across breeds exists, and the disease heritage of mixed breed dogs remains poorly explored to date. Advances in genetic screening technologies now enable comprehensive investigations of the canine disease heritage, and generate health-related big data that can be turned into action.

We pursued population screening of genetic variants implicated in Mendelian disorders in the largest canine study sample examined to date by examining over 83,000 mixed breed and 18,000 purebred dogs representing 330 breeds for 152 known variants using a custom-designed beadchip microarray. We further announce the creation of MyBreedData, an online updated inherited disorder prevalence resource with its foundation in the generated data.

We identified the most prevalent, and rare, disease susceptibility variants across the general dog population while providing the first extensive snapshot of the mixed breed disease heritage. Approximately two in five dogs carried at least one copy of a tested disease variant. Most disease variants are shared by both mixed breeds and purebreds, while breed-specificity or line-specificity of others is strongly suggested. Mixed breed dogs were more likely to carry a common recessive disease, whereas purebreds were more likely to be genetically affected with one, providing DNA-based evidence for hybrid vigor. We discovered genetic presence of 22 disease variants in at least one additional breed in which they were previously undescribed. Some mutations likely manifest similarly independently of breed background; however, we emphasize the need for follow up investigations in each case and provide a suggested validation protocol for broader consideration. In conclusion, our study provides unique insight into genetic epidemiology of canine disease risk variants, and their relevance for veterinary medicine, breeding programs and animal welfare.

Author summary:

Like any human, dogs may suffer from or pass on a variety of inherited disorders. Knowledge of how likely a typical dog is to carry an inherited disorder in its genome, and which disorders are the most common and relevant ones across dog breeds, is valuable for both veterinary care and breeding of healthy dogs.

We have explored the largest global dog study sample collected to date, consisting of more than 100,000 mixed breed and purebred dogs, to advance research on this subject. We found that mixed breed dogs and purebred dogs potentially suffer from many of the same inherited disorders, and that around two in five dogs carried at least one of the conditions that we screened for. A dog carrying an inherited disorder is not a “bad dog”—but we humans responsible for breeding selections do need to make sustainable decisions avoiding inbreeding, ie. mating of dogs that are close relatives. The disease prevalence information we generated during this study is made available online (www.mybreeddata.com [now defunct?]), as a free tool for breed and kennel clubs, breeders, as well as the veterinary and scientific community.

“Gene Editing Restores Dystrophin Expression in a Canine Model of Duchenne Muscular Dystrophy”, Amoasii1 et al 2018

2018-amoasii.pdf: “Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy”⁠, Leonela Amoasii1, John C. W. Hildyard, Hui Li, Efrain Sanchez-Ortiz, Alex Mireault, Daniel Caballero et al (2018; gene editing; similar):

Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation corresponding to a mutational “hotspot” in the human DMD gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (n = 2) or 8 weeks after systemic delivery (n = 2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90% of normal, depending on muscle type. In cardiac muscle, dystrophin levels in the dog receiving the highest dose reached 92% of normal. The treated dogs also showed improved muscle histology. These large-animal data support the concept that, with further development, gene editing approaches may prove clinically useful for the treatment of DMD.

“Heritability of Behavioural Traits in Domestic Dogs: A Meta-analysis”, Hradecká et al 2018

2015-hradecka.pdf: “Heritability of behavioural traits in domestic dogs: A meta-analysis”⁠, Lenka Hradecká, Luděk Bartoš, Ivona Svobodová, James Sales (2018-01-01; backlinks)

“Genetic Correlations of Hip Dysplasia Scores for Golden Retrievers and Labrador Retrievers in France, Sweden and the UK”, Wang et al 2017

2017-wang.pdf: “Genetic correlations of hip dysplasia scores for Golden retrievers and Labrador retrievers in France, Sweden and the UK”⁠, S. Wang, G. Leroy, S. Malm, T. Lewis, Å. Viklund, E. Strandberg, W. F. Fikse (2017-08-01; heritability / correlation):

• Hip dysplasia (HD) genetic parameters were estimated for 2 dog breeds in France, Sweden and the UK.
• Estimates of heritability ranged from 0.15 to 0.41, according to breed and country.
• The power of estimation was highly associated with the connectedness between populations.
• Genetic progress to reduce the prevalence of HD could be improved by selection across countries.
• Estimated genetic correlations of HD scores demonstrated the feasibility of international evaluation.

In order to reduce the prevalence of inherited diseases in pedigree dogs, the feasibility of implementation of an international breeding program was investigated. One prerequisite is a strong genetic correlation between countries and our objective was to estimate this correlation for canine hip dysplasia (HD) across 3 countries to evaluate the feasibility of an international genetic evaluation. Data were provided by the Société Centrale Canine (SCC, France), Svenska Kennelklubben (SKK, Sweden) and The Kennel Club (KC, UK) on Golden retriever and Labrador retriever dogs. Trivariate analysis on the 3 different modes of scoring HD in France, Sweden and the UK was performed using a mixed linear animal model. Heritability, genetic correlation, number of common sires, genetic similarity, selection differentials and accuracy of selection were calculated.

The estimated heritabilities of Golden retrievers (Labrador retrievers) for HD scores were 0.28 (0.15), 0.28 (0.29) and 0.41 (0.34) in France, Sweden and the UK, respectively. The feasibility of performing a genetic evaluation of HD across countries was indicated by the favourable genetic correlations estimated between score modes (ranged from 0.48 to 0.99). The accuracy of selection for the most recent birth year cohorts of male dogs was not improved by international evaluation compared to national evaluation.

Improvement in genetic progress can however be achieved by selection across populations in different countries, particularly for small populations, which were indicated by the large difference between selection differentials based on the national and international evaluations.

[Keywords: best linear unbiased prediction (BLUP), dog, genetic correlation, hip dysplasia, international breeding program]

“Selective Sweep Analysis Using Village Dogs Highlights the Pivotal Role of the Neural Crest in Dog Domestication”, Pendleton et al 2017

“Selective sweep analysis using village dogs highlights the pivotal role of the neural crest in dog domestication”⁠, Amanda L. Pendleton, Feichen Shen, Angela M. Taravella, Sarah Emery, Krishna R. Veeramah, Adam R. Boyko et al (2017-03-21; genetics / selection / artificial⁠, neuroscience; similar):

Dogs (Canis lupus familiaris) were domesticated from gray wolves between 20–40kya in Eurasia, yet details surrounding the process of domestication remain unclear. The vast array of phenotypes exhibited by dogs mirror numerous other domesticated animal species, a phenomenon known as the Domestication Syndrome. Here, we use signatures persisting in the dog genome to identify genes and pathways altered by the intensive selective pressures of domestication. We identified 37 candidate domestication regions containing 17.5Mb of genome sequence and 172 genes through whole-genome SNP analysis of 43 globally distributed village dogs and 10 wolves. Comparisons with three ancient dog genomes indicate that these regions reflect signatures of domestication rather than breed formation. Analysis of genes within these regions revealed a significant enrichment of gene functions linked to neural crest cell migration, differentiation and development. Genome copy number analysis identified regions of localized sequence and structural diversity, and discovered additional copy number variation at the amylase-2b locus. Overall, these results indicate that primary selection pressures targeted genes in the neural crest as well as components of the minor spliceosome, rather than genes involved in starch metabolism. Smaller jaw sizes, hairlessness, floppy ears, tameness, and diminished craniofacial development distinguish wolves from domesticated dogs, phenotypes of the Domestication Syndrome that can result from decreased neural crest cells at these sites. We propose that initial selection acted on key genes in the neural crest and minor splicing pathways during early dog domestication, giving rise to the phenotypes of modern dogs.

“Demographic History, Selection and Functional Diversity of the Canine Genome”, Ostrander et al 2017

2017-ostrander.pdf: “Demographic history, selection and functional diversity of the canine genome”⁠, Elaine A. Ostrander, Robert K. Wayne, Adam H. Freedman, Brian W. Davis (2017-01-01; genetics / selection / artificial)

“Evolutionary History, Selective Sweeps, and Deleterious Variation in the Dog”, Freedman et al 2016

2016-wayne.pdf: “Evolutionary History, Selective Sweeps, and Deleterious Variation in the Dog”⁠, Adam H. Freedman, Kirk E. Lohmueller, Robert K. Wayne (2016-01-01; genetics / selection / artificial)

“Comparative Analysis of the Domestic Cat Genome Reveals Genetic Signatures Underlying Feline Biology and Domestication”, Montague et al 2014

2014-montague.pdf: “Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication”⁠, Michael J. Montague, Gang Li, Barbara Gandolfi, Razib Khan, Bronwen L. Aken, Steven M. J. Searle, Patrick Minx et al (2014-10-03; cat genetics⁠, genetics / selection / artificial⁠, psych / smell; backlinks; similar):

Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae.

“A Simple Genetic Architecture Underlies Morphological Variation in Dogs”, Boyko et al 2010

“A Simple Genetic Architecture Underlies Morphological Variation in Dogs”⁠, Adam R. Boyko, Pascale Quignon, Lin Li, Jeffrey J. Schoenebeck, Jeremiah D. Degenhardt, Kirk E. Lohmueller et al (2010-07-02; genetics / selection / artificial; similar):

Domestic dogs exhibit tremendous phenotypic diversity, including a greater variation in body size than any other terrestrial mammal. Here, we generate a high density map of canine genetic variation by genotyping 915 dogs from 80 domestic dog breeds, 83 wild canids, and 10 outbred African shelter dogs across 60,968 single-nucleotide polymorphisms (SNPs).

Coupling this genomic resource with external measurements from breed standards and individuals as well as skeletal measurements from museum specimens, we identify 51 regions of the dog genome associated with phenotypic variation among breeds in 57 traits. The complex traits include average breed body size and external body dimensions and cranial, dental, and long bone shape and size with and without allometric scaling. In contrast to the results from association mapping of quantitative traits in humans and domesticated plants, we find that across dog breeds, a small number of quantitative trait loci (≤3) explain the majority of phenotypic variation for most of the traits we studied. In addition, many genomic regions show signatures of recent selection, with most of the highly differentiated regions being associated with breed-defining traits such as body size, coat characteristics, and ear floppiness.

Our results demonstrate the efficacy of mapping multiple traits in the domestic dog using a database of genotyped individuals and highlight the important role human-directed selection has played in altering the genetic architecture of key traits in this important species.

Author Summary: Dogs offer an unique system for the study of genes controlling morphology. DNA from 915 dogs from 80 domestic breeds, as well as a set of feral dogs, was tested at over 60,000 points of variation and the dataset analyzed using novel methods to find loci regulating body size, head shape, leg length, ear position, and a host of other traits. Because each dog breed has undergone strong selection by breeders to have a particular appearance, there is a strong footprint of selection in regions of the genome that are important for controlling traits that define each breed. These analyses identified new regions of the genome, or loci, that are important in controlling body size and shape. Our results, which feature the largest number of domestic dogs studied at such a high level of genetic detail, demonstrate the power of the dog as a model for finding genes that control the body plan of mammals. Further, we show that the remarkable diversity of form in the dog, in contrast to some other species studied to date, appears to have a simple genetic basis dominated by genes of major effect.

“An Expressed fgf4 Retrogene Is Associated With Breed-defining Chondrodysplasia in Domestic Dogs.”, Parker et al 2009

“An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs.”⁠, Parker, Heidi G. VonHoldt, Bridgett M. Quignon, Pascale Margulies, Elliott H. Shao, Stephanie Mosher et al (2009-08-21; heritability / rare-variants; similar):

Retrotransposition of processed mRNAs is a common source of novel sequence acquired during the evolution of genomes. Although the vast majority of retroposed gene copies, or retrogenes, rapidly accumulate debilitating mutations that disrupt the reading frame, a small percentage become new genes that encode functional proteins. By using a multibreed association analysis in the domestic dog, we demonstrate that expression of a recently acquired retrogene encoding fibroblast growth factor 4 (fgf4) is strongly associated with chondrodysplasia, a short-legged phenotype that defines at least 19 dog breeds including dachshund, corgi, and basset hound. These results illustrate the important role of a single evolutionary event in constraining and directing phenotypic diversity in the domestic dog.

“Genetic Variation in Aggression-related Traits in Golden Retriever Dogs”, Liinamo et al 2007

2007-liinamo.pdf: “Genetic variation in aggression-related traits in Golden Retriever dogs”⁠, Anna-Elisa Liinamo, Lindavan den Berg, Peter A. J. Leegwater, Matthijs B. H. Schilder, Johan A. M. van Arendonk et al (2007-04-01; backlinks; similar):

In this study, heritabilities of several measures of aggression were estimated in a group of 325 Golden Retrievers, using the Restricted Maximum Likelihood method. The studied measures were obtained either through owner opinions or by using the Canine Behavioural Assessment and Research Questionnaire (CBARQ). The aim of the study was to determine which of the aggression measures showed sufficient genetic variation to be useful as phenotypes for future molecular genetic studies on aggression in this population.

The most reliable heritability estimates seemed to be those for simple dog owner impressions of human-directed and dog-directed aggression, with heritability estimates of 0.77 (S.E. 0.09) and 0.81 (S.E. 0.09), respectively. In addition, several CBARQ-derived measures related to human-directed aggression showed clear genetic differences between the dogs. The correlation between the estimated breeding values for owner impressions on human-directed and dog-directed aggression was relatively low. The low correlation suggests that these two traits have a partially different genetic background. They will therefore have to be treated as separate traits in further genetic studies.

[Keywords: dogs, aggressive behaviour, questionnaire, heritability, estimated breeding values]

“Traits and Genotypes May Predict the Successful Training of Drug Detection Dogs”, Maejima et al 2007

2007-maejima.pdf: “Traits and genotypes may predict the successful training of drug detection dogs”⁠, Masami Maejima, Miho Inoue-Murayama, Keiichi Tonosaki, Naoto Matsuura, Shota Kato, Yasuhiro Saito, Alexander Weiss et al (2007; dog⁠, genetics / selection / artificial⁠, psych / personality; backlinks; similar):

In Japan, ~30% of dogs that enter training programs to become drug detection dogs successfully complete training. To clarify factors related to the aptitude of drug detection dogs and develop an assessment tool, we evaluated genotypes and behavioural traits of 197 candidate dogs. The behavioural traits were evaluated within 2 weeks from the start of training and included general activity, obedience training, concentration, affection demand, aggression toward dogs, anxiety, and interest in target. Principal components analysis of these ratings yielded two components: Desire for Work and Distractibility. Desire for Work was statistically-significantly related to successful completion of training (p < 0.001). Since 93.3% of dogs that passed training and 53.3% of the dogs that failed training had Desire for Work scores of 45 or higher, we will be able to reject about half of inappropriate dogs before 3 months of training by adopting this cut-off point. We also surveyed eight polymorphic regions of four genes that have been related to human personality dimensions. Genotypes were not related to whether dogs passed, but there was a weak relationship between Distractibility and a 5HTT haplotype (p < 0.05).

“Behavior Genetics of Canine Aggression: Behavioral Phenotyping of Golden Retrievers by means of an Aggression Test”, Guinness 2003

2003-vandenberg.pdf: “Behavior genetics of canine aggression: behavioral phenotyping of golden retrievers by means of an aggression test”⁠, Guinness (2003-01-01; dog⁠, psychology; backlinks)

“Behavior Genetics”, Takeuchi & Houpt 2003

2003-takeuchi.pdf: “Behavior genetics”⁠, Yukari Takeuchi, Katherine A. Houpt (2003-01-01; backlinks)

“Genetics of Quantitative Traits and Improvement of Dog Breeds”, Famula 2001

2001-famula.pdf: “Genetics of Quantitative Traits and Improvement of Dog Breeds”⁠, Thomas R. Famula (2001-01-01; genetics / selection / artificial)

“Genetics of Behaviour”, Houpt & Willis 2001

2001-houpt.pdf: “Genetics of Behaviour”⁠, Katherine A. Houpt, M. B. Willis (2001-01-01; backlinks)

“Early Canid Domestication: The Farm-Fox Experiment: Foxes Bred for Tamability in a 40-year Experiment Exhibit Remarkable Transformations That Suggest an Interplay between Behavioral Genetics and Development”, Trut 1999

“Early Canid Domestication: The Farm-Fox Experiment: Foxes bred for tamability in a 40-year experiment exhibit remarkable transformations that suggest an interplay between behavioral genetics and development”⁠, Lyudmila N. Trut (1999-03; index selection⁠, psych / personality; backlinks; similar):

[Popular review of the domesticated red fox by the lead researcher. Trut gives the history of Belyaev’s founding of the experiment in 1959, and how the results gradually proved his theory about ‘domestication syndrome’: that domestication produces multiple simultaneous effects like floppy ears despite the foxes being bred solely for being willing to approach a strange human, suggesting an underlying common genetic mechanism]

Forty years into our unique lifelong experiment, we believe that Dmitry Belyaev would be pleased with its progress. By intense selective breeding, we have compressed into a few decades an ancient process that originally unfolded over thousands of years. Before our eyes, “the Beast” has turned into “Beauty”, as the aggressive behavior of our herd’s wild progenitors entirely disappeared. We have watched new morphological traits emerge, a process previously known only from archaeological evidence. Now we know that these changes can burst into a population early in domestication, triggered by the stresses of captivity, and that many of them result from changes in the timing of developmental processes. In some cases the changes in timing, such as earlier sexual maturity or retarded growth of somatic characters, resemble pedomorphosis. Some long-standing puzzles remain. We believed at the start that foxes could be made to reproduce twice a year and all year round, like dogs. We would like to understand why this has turned out not to be quite so. We are also curious about how the vocal repertoire of foxes changes under domestication. Some of the calls of our adult foxes resemble those of dogs and, like those of dogs, appear to be holdovers from puppyhood, but only further study will reveal the details. The biggest unanswered question is just how much further our selective-breeding experiment can go. The domestic fox is not a domestic dog, but we believe that it has the genetic potential to become more and more doglike.

“The Use of a Behaviour Test for the Selection of Dogs for Service and Breeding, I: Method of Testing and Evaluating Test Results in the Adult Dog, Demands on Different Kinds of Service Dogs, Sex and Breed Differences”, Wilsson & Sundgren 1997

1997-wilsson.pdf: “The use of a behaviour test for the selection of dogs for service and breeding, I: Method of testing and evaluating test results in the adult dog, demands on different kinds of service dogs, sex and breed differences”⁠, Erik Wilsson, Per-Erik Sundgren (1997-01-01; dog⁠, genetics / selection / artificial; backlinks)

“The Use of a Behaviour Test for Selection of Dogs for Service and Breeding. II. Heritability for Tested Parameters and Effect of Selection Based on Service Dog Characteristics”, Wilsson & Sundgren 1997

1997-wilsson.pdf: “The use of a behaviour test for selection of dogs for service and breeding. II. Heritability for tested parameters and effect of selection based on service dog characteristics”⁠, Erik Wilsson, Per-Erik Sundgren (1997-01-01; backlinks)

“Environmental Effects and Genetic Parameters for Measurements of Hunting Performance in the Finnish Spitz”, Karjalainen et al 1996

1996-karjalainen.pdf: “Environmental effects and genetic parameters for measurements of hunting performance in the Finnish Spitz”⁠, L. Karjalainen, M. Ojala, V. Vilva (1996-01-01; heritability / correlation; backlinks)

“Genetic Aspects of Dog Behaviour With Particular Reference to Working Ability”, Willis 1995

1995-willis.pdf: “Genetic aspects of dog behaviour with particular reference to working ability”⁠, M. B. Willis (1995-01-01; backlinks)

“Canine Behavioral Genetics - A Review”, Mackenzie et al 1986

1986-mackenzie.pdf: “Canine Behavioral Genetics - A Review”⁠, Stephen A. Mackenzie, E. A. B. Oltenacu, K. A. Houpt (1986-01-01; backlinks)

“Heritability Estimate for Temperament Scores in German Shepherd Dogs and Its Genetic Correlation With Hip Dysplasia”, Mackenzie et al 1985

1985-mackenzie.pdf: “Heritability estimate for temperament scores in German shepherd dogs and its genetic correlation with hip dysplasia”⁠, Stephen A. Mackenzie, Elizabeth A. B. Oltenacu, Eldin Leighton (1985-01-01; dog⁠, heritability / correlation; backlinks)

“Genetic and Environmental Factors Affecting the Suitability of Dogs As Guide Dogs for the Blind”, Goddard & Beilharz 1982

1982-goddard.pdf: “Genetic and environmental factors affecting the suitability of dogs as Guide Dogs for the Blind”⁠, M. E. Goddard, R. G. Beilharz (1982-01-01; backlinks)

“Studies of the Inheritance of Intelligence and Temperament in Dogs”, Dawson et al 1965

1965-dawson.pdf: “Studies of the inheritance of intelligence and temperament in dogs”⁠, Dawson, Walker Myrick, 1902 (1965-01-01; IQ)

“Genetics and the Social Behavior of the Dog [Dog Behavior: The Genetic Basis]”, Scott & Fuller 1965

1965-scott-geneticsandthesocialbehaviorofthedog.pdf: “Genetics and the Social Behavior of the Dog [Dog Behavior: The Genetic Basis]”⁠, John Paul Scott, John L. Fuller (1965; cat genetics⁠, genetics / selection / artificial; backlinks; similar):

Classic study of dog behavior, the authoritative information from 20 years of research at the Jackson Laboratory. The authors synthesize developmental problems and canine genetics, based on study of 470 dogs. Central to the book is the role heredity plays in the development of behavior. Giving puppies an environment designed on the principles of a well-run school, Scott and Fuller tested five breeds representing the major dog groups and carried out a Mendelian experiment with two of the most different breeds: The basenji and the cocker spaniel. They found that heredity affects almost every trait tested; that gender affects aggressiveness and the dominance order, but not trainability and problem-solving; that emotional traits profoundly influence performance; that, although breeds differ widely in emotional and motivational characteristics, none shows distinct superiority in problem solving; and that detailed statistical analyses indicate a highly complex pathway between primary gene action and its final effect on behavior. Includes important information on rearing methods, the origin and history of dog breeds, basic behavior patterns and the psychological and behavioral development of puppies. Their careful scientific work demonstrated the importance and existence of time limited phases in the early life of dogs within which certain experiences need to occur or the dogs may be forever deficient. Their work (with that of Eckhard Hess’s on ducks and geese) demonstrated that these critical or sensitive periods in early development could be scientifically studied in ways compatible with a scientific psychology. This book will always be especially valuable to dog breeders and trainers; its last chapters summarize in very clear terms the particular phases in early development and experiences the dog needs to be adequately socialized. The reader can refer back to earlier chapters to get more information on how the experiments were conducted and the distribution of results. It answers questions on proper age that puppies can be separated from their mothers, what experiences are important to provide at what age, etc. Originally published in 1965. [ISBN: 0–226–74335–7]