Comparative review of human and canine osteosarcoma: morphology, epidemiology, prognosis, treatment and genetics

Osteosarcoma (OSA) is a rare cancer in people. However OSA incidence rates in dogs are 27 times higher than in people. Prognosis in both species is poor, with five year osteosarcoma survival rates in people not having improved in decades. For dogs, one year survival rates are only around ~45%. Improved and novel treatment regimens are urgently required to improve survival in both humans and dogs with OSA. Utilising information from genetic studies could assist in this in both species, with the higher incidence rates in dogs contributing to the dog population being a good model of human disease. This review compares the clinical characteristics, gross morphology and histopathology, aetiology, epidemiology, and genetics of canine and human osteosarcoma. Finally, the current position of canine osteosarcoma genetic research is discussed and areas for additional work within the canine population are identified

GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans

On the hunt for the gene of perspective taking: pitfalls in methodology

In this commentary, we evaluate the methodology of Udell, Dorey, and Wynne’s (Learning & Behavior, in press) experiment in controlling for environmental factors and argue that their conclusion is not supported. In particular, we emphasise that comparative studies on dogs and wolves need to ensure that both species enjoyed the same rearing history, are comparable in age, and have the same experience with the testing conditions. We also argue that the utilisation of shelter dogs does not control for genetic effects on social behaviour. Finally, we propose a synergetic model to account for both genetic and environmental effects on interspecific social behaviour in dogs and wolves

The wolf reference genome sequence (Canis lupus lupus) and its implications for Canis spp. population genomics

Background: An increasing number of studies are addressing the evolutionary genomics of dog domestication, principally through resequencing dog, wolf and related canid genomes. There is, however, only one de novo assembled canid genome currently available against which to map such data - that of a boxer dog (Canis lupus familiaris). We generated the first de novo wolf genome (Canis lupus lupus) as an additional choice of reference, and explored what implications may arise when previously published dog and wolf resequencing data are remapped to this reference. Results: Reassuringly, we find that regardless of the reference genome choice, most evolutionary genomic analyses yield qualitatively similar results, including those exploring the structure between the wolves and dogs using admixture and principal component analysis. However, we do observe differences in the genomic coverage of re-mapped samples, the number of variants discovered, and heterozygosity estimates of the samples. Conclusion: In conclusion, the choice of reference is dictated by the aims of the study being undertaken; if the study focuses on the differences between the different dog breeds or the fine structure among dogs, then using the boxer reference genome is appropriate, but if the aim of the study is to look at the variation within wolves and their relationships to dogs, then there are clear benefits to using the de novo assembled wolf reference genome.Carlsbergfondet grant CF14–0995 and Marie Curie grant 655732-Wherewolf to SG, Danish National Research Foundation grant DNRF94, Lundbeckfonden grant R52–5062 and ERC Consolidator Grant (681396-Extinction Genomics) (to MTPG) and the Swedish Research Council (to LD). LFKK is supported by an FPI fellowship associated to BFU2014–55090-P (FEDER). TMB is supported by MINECO BFU2014–55090-P (FEDER), Fundacio Zoo Barcelona and Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya. GL was supported by a European Research Council grant (ERC-2013-StG-337574-UNDEAD) and Natural Environmental Research Council grants (NE/K005243/1 and NE/K003259/1)