Genetic dissection of complex behaviour traits in German Shepherd dogs

Friedrich, Juliane; Strandberg, E.; Arvelius, Per; Sánchez-Molano, Enrique; Pong‐Wong, Ricardo; Hickey, John M.; Haskell, Marie J.; Wiener, Pamela

doi:10.1038/s41437-019-0275-2

Cited by 23 publications

(30 citation statements)

References 65 publications

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“…Domestic dogs have lived alongside humans for at least 10,000 years 1 , 2 , and during this time, they have adapted to a shared environment and diet, while being selectively bred for traits such as morphology 3 and behaviour 4 . Humans and dogs also share orthologous genes, genomic architecture and disease sets, placing the dog as an important comparative species for human genetics and genomics.…”

Section: Introductionmentioning

confidence: 99%

A novel canine reference genome resolves genomic architecture and uncovers transcript complexity

et al. 2021

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We present GSD_1.0, a high-quality domestic dog reference genome with chromosome length scaffolds and contiguity increased 55-fold over CanFam3.1. Annotation with generated and existing long and short read RNA-seq, miRNA-seq and ATAC-seq, revealed that 32.1% of lifted over CanFam3.1 gaps harboured previously hidden functional elements, including promoters, genes and miRNAs in GSD_1.0. A catalogue of canine “dark” regions was made to facilitate mapping rescue. Alignment in these regions is difficult, but we demonstrate that they harbour trait-associated variation. Key genomic regions were completed, including the Dog Leucocyte Antigen (DLA), T Cell Receptor (TCR) and 366 COSMIC cancer genes. 10x linked-read sequencing of 27 dogs (19 breeds) uncovered 22.1 million SNPs, indels and larger structural variants. Subsequent intersection with protein coding genes showed that 1.4% of these could directly influence gene products, and so provide a source of normal or aberrant phenotypic modifications.

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Section: Introductionmentioning

confidence: 99%

A novel canine reference genome resolves genomic architecture and uncovers transcript complexity

et al. 2021

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“…The research field of the genetics of dog behavior trait is of much interest, because dogs are unique animal models that can be used to understand behavioral traits 31 . However, there are a limited number of studies 32,33 , because assessment of behavioral traits is a difficult task. In this study, we used subjective judgment from dog handlers.…”

Section: Discussionmentioning

confidence: 99%

Genome wide association study of 40 clinical measurements in eight dog breeds

Momozawa

Merveille

Battaille

et al. 2020

Sci Rep

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The domestic dog represents an ideal model for identifying susceptibility genes, many of which are shared with humans. In this study, we investigated the genetic contribution to individual differences in 40 clinically important measurements by a genome-wide association study (GWAS) in a multinational cohort of 472 healthy dogs from eight breeds. Meta-analysis using the binary effects model after breed-specific GWAS, identified 13 genome-wide significant associations, three of them showed experimental-wide significant associations. We detected a signal at chromosome 13 for the serum concentration of alanine aminotransferase (ALT) in which we detected four breed-specific signals. A large proportion of the variance of ALT (18.1-47.7%) was explained by this locus. Similarly, a single SNP was also responsible for a large proportion of the variance (6.8-78.4%) for other measurements such as fructosamine, stress during physical exam, glucose, and morphometric measurements. The genetic contribution of single variant was much larger than in humans. These findings illustrate the importance of performing meta-analysis after breed-specific GWAS to reveal the genetic contribution to individual differences in clinically important measurements, which would lead to improvement of veterinary medicine. The domestic dogs share many diseases and phenotypes with human 1. Through two bottlenecks resulting from domestication 2 and the frequent use of specific males, each dog breed shows lower heterogeneity for disease. In humans, higher heterogeneity, meaning multiple variants with different levels of effects influencing the same disease, makes it difficult to identify genetic variants associated with disease 3. Therefore, dogs are considered an ideal model animal for identifying genes and genomic loci underlying diseases and phenotypic variation 1,4. Genome-wide association studies (GWAS) using canine single nucleotide polymorphism (SNP) chips have identified susceptibility genes and genomic loci for several complex diseases 5-10 and for many Mendelian disorders 11-16. The diagnosis of a disease often involves taking many clinical measurements including blood and urine analysis. These measurements directly reflect different aspects of the health of each individual. Individual differences in these measurements are known to be heritable in humans, and GWAS have identified genetic loci explaining these individual differences 17. A systematic analysis of 6,046 dogs has identified breed-specific differences in hematological measurements 18 , suggesting also a genetic contribution to the inter-breed variation for these

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“…Recently, a small improvement in accuracy of genomic selection was seen for UK dogs in a joint genomic prediction of Norberg Angle score (one of diagnostic characteristics of HD) between US and UK Labrador retrievers (16); thus, future research could focus on joint genomic selection of HD between BVA/KC and FCI schemes. In addition, a genome-wide association study of canine behavior traits has been performed on a combined dataset of the UK and Swedish GSD populations (17), which suggests the potential to examine genetic factors influencing HD by performing a joint-population association analysis using a univariate model across countries/schemes (e.g., by converting BVA/KC scores in the UK population into FCI grades). This would give the potential to gain further insights into the genetic architecture of HD.…”

Section: Discussionmentioning

confidence: 99%

Methods to Improve Joint Genetic Evaluation of Canine Hip Dysplasia Across BVA/KC and FCI Screening Schemes

et al. 2020

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The BVA/KC (British Veterinary Association/Kennel Club) and FCI (Fédération Cynologique Internationale) are the main screening schemes used to evaluate the status of canine hip dysplasia (HD) in Europe. Jointly utilizing HD records from both BVA/KC and FCI schemes could improve the reliability of genetic evaluation within and across countries. In this study, HD scores for German shepherd dogs (GSDs) in the UK (using the BVA/KC scheme) and Sweden (using the FCI scheme) were used to investigate how to better operate joint genetic evaluations across the two schemes. It was shown that under a bivariate model, which regarded BVA/KC and FCI scores as different traits, the estimated genetic correlations between the UK and Swedish GSD populations were the same when using BVA/KC total or worse hip scores and for single-country or joint analysis of both the UK and Swedish populations. Under a univariate model that converted BVA/KC scores into FCI scores, the predictability of estimated breeding values was slightly improved by performing a joint analysis.

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Genetic dissection of complex behaviour traits in German Shepherd dogs

Cited by 23 publications

References 65 publications

A novel canine reference genome resolves genomic architecture and uncovers transcript complexity

A novel canine reference genome resolves genomic architecture and uncovers transcript complexity

Genome wide association study of 40 clinical measurements in eight dog breeds

Methods to Improve Joint Genetic Evaluation of Canine Hip Dysplasia Across BVA/KC and FCI Screening Schemes

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