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Department of Veterinary Medicine

Cambridge Veterinary School
 

Comparative genetics of inherited disease specialising in BOAS, breed predisposition to cancer and eye diseases

My lab is interested in comparative genetics of disease and in particular in genetic diseases of dogs. We believe that understanding canine models will throw light on human disease, whilst also allowing us to develop veterinary insights and better advice for breeders.

  • Pathogenesis of retinal and other ocular inherited disease.
  •  Canine breed predispostion to “complex” genetic diseases, especially brachycephalic obstructive airway syndrome (BOAS) and cancer.
  • Secondary epigenetic and somatic genetic change in complex inherited diseases.
  • Comparative genomic mapping in companion and exotic animal species.
  • Technical development of mapping and genetic analysis methods.
  • Genetic aspects of welfare issues for dog breeds.

Biography

Dr Sargan studied Natural Sciences and Genetics as an undergraduate in Cambridge, went to UCL for a PhD in Biochemistry, studying interactions of RNA polymerare II with chromatin during transcription, then undertook postdoctoral studies in University of Geneva and Baylor College of Medicine, Houston before taking up a lectureship at the R(D)SVS Edinburgh, and moving back to Cambridge in 1994.

Research

One major current study is centred on uncovering the genetics of BOAS. This is a complex disease of the upper airway in short-faced dogs, which, if left untreated, can give complications ranging from exercise intolerance to food regurgitation, inability to sleep normally, heat stroke, and death. In the past, a major problem in understanding the disease has been that diagnosis is complex because there has been no absolute agreement as to how respiratory noises (snoring and snorting) in affected breeds correlate with functional respiratory disease.

A close collaboration with Dr Jane Ladlow and Dr Nai-chieh Liu, has developed objective tools to measure effectiveness of respiratory cycles in pugs, French bulldogs and bulldogs using whole body barometric plethysmography. At the same time the group has measured conformation of the head and of parts of the airway in these same dogs.

To look at genetic changes associated with the differences we measure between BOAS affected and normal animals, we are carrying out genome wide association studies (GWAS) in each breed to locate genes important to the disease within the genome, led by Dr Lajos Kalmar.

We are now comparing those regions of the genome implicated in this study in greater detail, in order to identify the particular genes and mutations that are associated with the disease. The frequency of each mutation in the population at risk, as well as the additional relative risk from each mutation will then be assessed. This will allow the development of advice to breeders based on estimating genetic breeding values associated with DNA profiles containing combinations of different mutations.

In addition, by analysing biopsy material from affected dogs and relating our findings to the GWAS results, we hope to develop a biological understanding of changes occurring in cartilage and soft tissues of the airway, which will feed through to wider and more appropriate options for therapy.

Additional studies are looking at miRNA signatures of canine tumours, and at genetics of the blinding inherited disease of dogs and cats, progressive retinal atrophy: an equivalent of human retinitis pigmentosa. I also collaborate with Prof Wood and others in studies of distribution of bat species that may act as viral disease vectors in tropical Africa using population genetic techniques. I curate a website aiming to collate the genetic basis of inherited disease traits in dogs

Publications

Key publications: 

A LINE-1 insertion situated in the promoter of IMPG2 is associated with autosomal recessive progressive retinal atrophy in Lhasa Apso dogs. Hitti-Malin RJ, Burmeister LM, Ricketts SL, Lewis TW, Pettitt L, Boursnell M, Schofield EC, Sargan D, Mellersh CS.BMC Genet. 2020 Sep 7;21(1):100. doi: 10.1186/s12863-020-00911-w.

Health-related welfare prioritisation of canine disorders using electronic health records in primary care practice in the UK. Summers JF, O'Neill DG, Church D, Collins L, Sargan D, Brodbelt DC. BMC Vet Res. 2019 May 22;15(1):163. doi: 10.1186/s12917-019-1902-0.

Whole Genome Sequencing of Giant Schnauzer Dogs with Progressive Retinal Atrophy Establishes NECAP1 as a Novel Candidate Gene for Retinal Degeneration. Hitti RJ, Oliver JAC, Schofield EC, Bauer A, Kaukonen M, Forman OP, Leeb T, Lohi H, Burmeister LM, Sargan D, Mellersh CS. Genes (Basel). 2019 May 21;10(5). pii: E385. doi: 10.3390/genes10050385.

Validation of exercise testing and laryngeal auscultation for grading brachycephalic obstructive airway  syndrome in pugs, French bulldogs, and English bulldogs by using whole-body barometric plethysmography. Riggs J, Liu NC, Sutton DR, Sargan D, Ladlow JF. Vet Surg. 2019 May;48(4):488-496. doi: 10.1111/vsu.13159. Epub 2019 Jan 21.

The Gambian epauletted fruit bat shows increased genetic divergence in the Ethiopian highlands and in an area of rapid urbanization. Riesle-Sbarbaro SA, Amponsah-Mensah K, de Vries S, Nicolas V, Lalis A, Suu-Ire R, Cunningham AA, Wood JLN, Sargan DR. Ecol & Evol. 2018 Dec 11;8(24):12803-12820. doi: 10.1002/ece3.4709. eCollection 2018 Dec.

Objective effectiveness of  and indications for laser-assisted turbinectomy in brachycephalic obstructive airway syndrome.  Liu NC, Genain MA, Kalmar L, Sargan DR, Ladlow JF. Vet Surg. 2019 Jan;48(1):79-87. doi: 10.1111/vsu.13107. Epub 2018 Oct 10.

Prevalence, duration and risk factors for appendicular osteoarthritis in a UK dog population under primary veterinary care. Anderson KL, O'Neill DG, Brodbelt DC, Church DB, Meeson RL, Sargan D, Summers  JF, Zulch H, Collins LM. Sci Rep. 2018 Apr 4;8(1):5641. doi: 10.1038/s41598-018-23940-z.

Brachycephalic obstructive airway syndrome. Ladlow J, Liu NC, Kalmar L, Sargan D.Vet Rec. 2018 Mar 31;182(13):375-378. doi: 10.1136/vr.k1403.

Canine genome assembly correction facilitates identification of a MAP9 deletion as a potential age of onset modifier for RPGRIP1 associated canine retinal degeneration Forman OP, Hitti R, Boursnell M, Miyadera K, Sargan DR, Mellersh C. (2016) . Mammalian Genome, 2016 Jun; 27 (5-6): 237-45 

Whole-body barometric plethysmography characterises upper airway obstructions in 3 brachycephalic breeds of dog. Liu NC Adams VJ, Kalmar L, Ladlow JF1, Sargan DR1*. J Vet Internal Medicine, 2016 May; 30(3):853-65. doi: 10.1111/jvim.13933. 1Both authors contributed equally. *Corresponding author

Continent-wide panmixia of an African fruit bat facilitates transmission of potentially-zoonotic viruses. Peel AJ, Sargan DR, Baker KS, Hayman DTS, Barr JA, Crameri G, Suu-Ire R, Broder CC, Wang L-F, Fooks AR, Rossiter SJ, Wood JLN & Cunningham AA. (2013)  Nature Commun. 4: 2770. doi: 10.1038/ncomms3770.

Multiple Mechanisms Contribute to Leakiness of a Frameshift Mutation in Canine Cone-Rod Dystrophy. Miyadera K, Brierley I, Aguirre-Hernández J, Mellersh CS and Sargan DR. (2012) PLoS One 7(12): e51598

Internet resources cataloguing inherited disorders in dogs (Review) Nicholas FW, Crook A, Sargan DR (2011) Veterinary J. 189(2):132-5

Other publications: 

The genetics of brachycephaly, population genetics and current health testing for brachycephalic breeds. Sargan D. Chapter 8 In Health and Welfare of Brachycephalic (Flat-faced ) Companion Animals: A complete guide for Veterinary and Animal Professionals eds Packer RMA & O’Neill DG CRC Press, 2021 pp 107-126.   ISBNs 978-0-367-20741-0 (hbk); 978-0-367-20724-3(pbk); 978-0-429-26323-1 (ebk)

Endotracheal tube placement during computed tomography of brachycephalic dogs alters upper airway dimensional measurements. Liu NC, Troconis EL, McMillan M, Genain MA, Kalmar L, Price DJ, Sargan DR, Ladlow JF. Vet Radiol Ultrasound. 2018 May;59(3):289-304. doi: 10.1111/vru.12590. Epub 2018 Jan 15.

Comprehensive annotation and evolutionary insights into the canine (Canis lupus familiaris) antigen receptor loci. Martin J, Ponstingl H, Lefranc MP, Archer J, Sargan D, Bradley A.  Immunogenetics. 2018 Apr;70(4):223-236. doi: 10.1007/s00251-017-1028-0. Epub 2017 Sep 19.  

Conformational risk factors of brachycephalic obstructive airway syndrome (BOAS) in pugs, French bulldogs, and bulldogs. Liu NC, Troconis EL, Kalmar L, Price DJ, Wright HE, Adams VJ, Sargan DR, Ladlow JF. PLoS One. 2017 Aug 1;12(8):e0181928. doi: 10.1371/journal.pone.0181928. eCollection 2017.

Objective evaluation of prognostic factors for surgical interventions in treating brachycephalic obstructive airway syndrome. Liu NC, Oechtering GU, Adams VJ, Kalmar L, Sargan DR, Ladlow JF.  Veterinary Surgery, 2017 Feb;46(2):271-280. doi: 10.1111/vsu.12608.

Bat trait, genetic and pathogen data from large-scale investigations of African fruit bats, Eidolon helvum. Peel AJ, Baker KS, Hayman DT, Suu-Ire R, Breed AC, Gembu GC, Lembo T, Fernández-Loras A, Sargan DR, Fooks AR, Cunningham AA, Wood JL. Sci Data. Cathy 2016 Aug 1;3:160049. doi: 10.1038/sdata.2016.49

Teaching and Supervisions

Teaching: 

MIMS 1A: PBL Lent term: Etiology and parthogenesis of cancers of the skin in veterinary species:

Postgraduate courses (Various) 

Research supervision: 

Julie Szu-Ting Lin to PhD "Use of Cone-Beam Computerised Tomography in the assessment of fetlock injury and its development" With Dr Rachel Murray (Rossdales)

Other Professional Activities

External examiner Glassgow Veterinary School Y3 course: Molecular Biology of Cancer

Trustee: Universities Federation for Animal Welfare

Trustee: Humane Slaughter Association

Associate Professor in Molecular Pathology
Director of Graduate Education
Chair, Training Committee, BBSRC Cambridge Bioscience DTP and SBS Cambridge Bioscience DTP
Takes PhD students
Available for consultancy

Affiliations

Classifications: 
Local Affiliations: 
Person keywords: 
Genomics
Canine
Brachycephalic Obstructive Airway Syndrome
miRNA expression profiles
Retinal degenerations
GWAS
Obesity
Sarcoma
Equine
Funding: 
Isaac Newton Trust
Kennel Club Charitable Trust