Edinburgh Research Explorer

Dr Jeffrey Schoenebeck

Chancellors Fellow

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Phone: +44 (0)131 651 9248

Willingness to take Ph.D. students: Yes

1) Morphological and genetic analysis of companion animal skeletal structures 2) Canine skeletal remodelling 3) Genetics of canine portsystemic shunts 4) Genomic Approaches to Identifying the Genetic Burden of the Labrador Retriever

Education/Academic qualification

Doctor in Philosophy, New York University School of Medicine
"Mechanisms of regulating latent cardiac potential in the anterior lateral plate mesoderm."
Bachelor of Science, The Pennsylvania State University

Area of Expertise

Research expertisecanine genetics and genomics, canine morphology, canine diseases and heritable traits

Current Research Interests

Genetic, genomic, and phenotyping approaches to studying the biological mechanisms that underlie canine morphology and disease.

Teaching

Animal Body 1 - Lecturer/examiner. Teach concepts of DNA, RNA, and protein to R(D)SVS first year veterinary students.

Animal Body 4 - examiner of student research projects.

Research Groups

Dog Biomedical Variant Database Consortium - member in pre-publication data sharing consortium of international dog geneticists.

Research Interests

1. The domestic dog is arguably the most divererse single species of animals to work the Earth. My group is interested in the genetic basis biological paradigms of this remarkable animal's skeletal morphology. To this end, we apply cutting edge diagnostic imaging, geometric morphometrics, and genomics to quantify the contributions of quantative trait loci (QTL) that alter dog skeletal size and shape. Using fine mapping approaches such as imputation, haplotype phasing, and whole genome sequencing, we endeavor to identify genetic variation that alters bone production and its morphogenesis. The goal of this research touches upon a number of themes including 1) to address improve companion animal welfare, in doing so increasing lifespan and physical activity, 2 ) through comparative genetics bring attention to potential causes of human developmental anomalies and orthopedic conditions, and 3) to understand the molecular basis of man's selective pressures on domesticated animals.

2. Genomics is awash with genetic variation that is associated with health and trait outcomes. Little of this genetic variation will be tested for its functional impacts because the systme in which it was discovered is intractable to such characterisations. The second goal of my group is to develop surrogate systems for characterising genetic variation discovered in non-traditional animals such as companion animals. We are interested in adapting existing animals models including zebrafish, chick, and mouse models, but as well, we are interested in developing cell culture based assays that utilise cell lines.

Biography

During my PhD, I became interested in how the balance between form and function manifests both genetically and morphologically with respect to body plans. In those days my model of choice was the zebrafish and the process was cardiac specification. It was in the laboratory of Dr. Deborah Yelon, then located at the Skirball Insitute (NYC, USA) that I began thinking about how cells respond to extrinsic and intrinsic factors to become specified to give rise to cardiac lineages. During this time, I applied cell lineage techniques to follow the cell contributions during embryogenesis. At the same time, I developed in situ techniques such as double fluorescence in situs to describe patterning of primordial tissues, specifically the lateral plate mesoderm. I studied fascinating ENU mutagenesis fish lines that had too little cardiac tissue or too much.

In 2007 I joined the Ostrander lab to start a postdoctoral fellowship. Based at the National Human Genome Research Institute (Bethesda, MD USA), I left the comforts of a "tractable" laboratory model. Rather, I joined a small group of peers who were interested in the genetic basis of dog traits and diseases. My focus quickly became skull shape, whose genetic basis was unknown in dogs. It was a naturally fit in many ways, as in my mind the diversity of skull shapes in dogs was merely the end product different developmental processes in these dogs.

In the Ostrander lab, we conducted genome-wide association tests to identify quantitative trait loci (QTL). This was rasther difficult to do in dogs, as high-quality measurement data from the skulls of dogs that we genotyped was unavailable. Rather, I measured breed representative skulls of dogs housed at various museums. While this approach proved useful in identifying some skull- and size-related QTL, further analysis to identify putatively causal DNA changes were often confounded.

In 2014 I moved to the Roslin Institute and R(D)SVS to begin my Chancellor's Fellowship. Here I had finally had access to the tools that would enable me to pursue morphological and genetic analyses in dogs with precision. Everyday at the R(D)SVS's Hospital for Small Animals, dog patients are receiving diganostic imaging to identify the causes of their ailments. In particular, computed tomography which is often used for orthopaedic conditions offers an unambigous view of the skeleton including the skull. My group specialises in the analyses of these images. Together with the analysis of each patient's DNA through various modalities including SNP arrays, DNA- and RNA-seq, we are able to isolate genetic changes in dogs that are likely to be responsible for dogs' dramatic variation in shape and sizes.  Moreover, our approach allows us to consider the morphology of any dog, pedigree or mixed-breed. With collaborators at both the Roslin Institute and Institute of Genetics and Molecular Medicine, we've begun to take what we learn from dogs to build mouse models that enable us to extend our findings by exploring the timing and location of gene activity.

Through our exploration of canine skull morphology, we've begun to extend our analysis to other aspects of the canine skeleton and explore the broader effects of genetic variants that dictate skull shape. We are also linking morphology to disease incidence in dogs, particularly as head shape influences breathing problems such as brachycephalic airway obstructive syndrome. Given the paradigm of genetic conservation that is commonly observed across species including man, we will continue to explore whether the genetic processes we uncover in dogs are also relevant to human conditions such as craniofacial anomalies.

 

My research in a nutshell

Morphology is a circular struggle between form and function. Natural selection ensures that one does not supersede the other. In the wild, the balance is a matter of life and death. In the custody of man, domesticated animals like the dog have pushed the boundary of form at the expense of function. I study dog skeletal morphology because no other species matches their diversity. Yet despite this radiation in morphological forms, the subpopulations that constitute pedigree animals are genetically simple, thus making them tractable to study the fundamentals of genetics. My group is interested in addressing a number of questions:

1. Why are dogs so diverse in the first place? What are the changes within DNA that enable their diversity in sizes and shapes? Dogs differ as much a forty-fold in size. A bullodg is radically different from a greyhound, and yet both are members of the same species and descendants of the grey wolf. What types of DNA mutations are responsible for these changes? Have certain DNA changes enabled dogs' plasticity?

2. How do mechanisms of restricting/promoting dog size and shape relate to fundamentals of bone biology? I am interested the genes responsible for making dogs so different from one another with respect to skeletal shape and size. By identifying molecular mechanisms underlying dog morphology, we will gain insights into developing therapeutics that are needed to modulate bone growth. Such therapeutics could have wide reach across species including man, from bone healing to controlling arthritis.

3. When do dogs' extreme forms conflict with their welfare? Bulldogs and other brachycephalic dog breeds are beloved worldwide. Yet their physical form is associated with devastating breathing conditions and other health challenges. As a society, when do dog forms run counter to their wellbeing? By understanding the genetics of dog morbidity, we aim to shed light on disease processes and propose informed, unbiased recommendations to address these health challenges.

4. Can dogs improve human health? Undoubtedly. In many respects, dogs are like humans. They experience the same environmental exposures that we do, they possess the same genes that we do, and they suffer from the same diseases that reduce our healthspan. In understanding the genetics responsible for reducing dog health, we will identify mechanisms that reduce our own health.

 

Research activities & awards

  1. Transcriptomic analysis of sheep macrophages and their response to lipopolysaccharide

    Activity: Examination typesExternal Examiner or Assessor

  2. Companion Animal Genetic Health (CAGH) conference 2018

    Activity: Participating in or organising an event typesParticipation in conference

  3. Companion Animal Genetic Health (CAGH) conference 2018

    Activity: Participating in or organising an event typesParticipation in conference

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