Department of Veterinary Medicine

Research in Veterinary Medicine

Other relevant links

• I curate the database Inherited Diseases in Dogs which collates peer reviewed descriptions of such diseases in the scientific and veterinary literature http://www.vet.cam.ac.uk/idid/

Research description

My laboratory 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. We have specialised in two areas: diseases of the eye and breed predispositions to cancer.

1) In the eye our current work is concentrated on cone rod dysplasia type one (a cone led retinal degeneration in which a polyA tract interrupts an exon of the RPGRIP1 gene). We are investigating why this apparently clear knock out of the gene has highly variable penetrance even when homozygous. In addition we are mapping the mutations causing lens luxation in terrier breeds and progressive retinal atrophy in several breeds.

2) Several dog breeds show clear predispositions to particular cancers, so that mapping the genes responsible could lead to better understanding of the mechanisms of these cancers and potentially to reductions in their incidence through DNA based testing. Currently we are investigating histiocytic sarcoma in flat-coated retrievers, anal sac adenocarcinoma in English cocker spaniels and haemangiosarcoma in German shepherd dogs.

Please contact Dr Sargan drs20@cam.ac.uk if you are interested in any of these projects.

Main collaborators

• Catheryn Mellersh and Mike Starkey, Animal Health Trust, Newmarket
• Elaine Ostrander, Human Genome Resources Institute, NIH
• Gerrard Rutteman, Utrecht
• Catherine Andre, Rennes
• Kerstin Lindblad-Toh, Broad Institute and Uppsala
• Nobuo Sasaki, Tokyo

Key publications since 2001

• Aguirre-Hernández J., Polton G., Kennedy L., Sargan D.R. 2010 Association between anal sac gland carcinoma and DLA-DQB1 in the English cocker spaniel. Tissue Antigens, accepted for publication.
• Aguirre-Hernández J., Sargan D.R. 2010 Multifocal Retinal Dysplasia in the German Spitz (Klein and Mittel) is not caused by mutations in BEST1. Animal Genetics, 41(3):333-34. First published online: DOI 10.1111/j.1365-2052.2009.02005.x [PubMed].
• Miyadera K., Kato K., Aguirre-Hernández J., Tokuriki T., Morimoto K., Busse C., Barnett K., Holmes N., Ogawa H., Sasaki N., Mellersh C.S., Sargan D.R. 2009 Phenotypic variation and genotype-phenotype discordance in canine cone-rod dystrophy with an RPGRIP1 mutation. Molecular Vision, 15:2287-2305. [PubMed] [Read Full Text].
• Aguirre-Hernández J., Milne B.S., Queen C., O'Brien P.C.M., Hoather T., Haugland S., Ferguson-Smith M., Dobson J.M., Sargan D.R. 2009 Disruption of chromosome 11 in canine fibrosarcomas highlights an unusual variability of CDKN2B in dogs. BMC Veterinary Research 2009, 5:27, doi:10.1186/1746-6148-5-27. [PubMed] [Read Full Text].
• Aguirre Hernández J., Wickstrom K., Sargan D.R. 2007 The Finnish lapphund retinal atrophy locus maps to the centromeric region of CFA9. BMC Veterinary Research 2007, 3:14. [PubMed] [Read Full Text].
• Sargan D.R., Withers D Pettitt L, Squire M, Gould DJ and Mellersh CM. (2007) Mapping the mutation causing lens luxation in several terrier breeds. J Heredity, 98:534-8. [PubMed] [Read Full Text].
• Sargan D.R., Aguirre-Hernández J, Galibert F and Ostrander EO. (2007) An extended microsatellite set for linkage mapping in the domestic dog. J Heredity, 98:221-31. [PubMed] [Read Full Text].
• Chase K, Sargan D.R., Miller K, Ostrander EO and Lark KG. (2006) Understanding the genetics of autoimmune disease: two loci that regulate late onset Addison's disease in Portuguese Water Dogs. Int J Immunogenet 33:179-184. [PubMed] [Read Full Text].
• Sargan D.R., Milne BS, Aguirre-Hernández J, O'Brien PCM, Malcolm A Ferguson-Smith MA, Tess Hoather T and Dobson JM (2005) Chromosome rearrangements in canine fibrosarcomas. J Heredity, 96:766-773. [PubMed] [Read Full Text].
• Borg I, Freude K, Kubart S, Hoffmann K, Menzel C, Laccone F, Ferguson Smith MA, Tommerup N, Ropers H-H, Sargan D.R. & Kalscheuer VM. (2005) Disruption of Netrin G1 by a balanced chromosome translocation in a girl with Rett Syndrome. Eur J Genet, 13(8):921-7. [PubMed].
• Aguirre-Hernández,J, Sargan D.R. (2005) Evaluation of candidate genes in the absence of positional information - A poor bet on a blind dog! J Heredity, 96:475-84. [PubMed] [Read Full Text].
• Milne BS, Hoather T, O'Brien PCM, Yang F, Ferguson-Smith MA, Dobson J, Sargan D.R. (2004) Karyotype of canine soft tissue sarcomas: a multi-colour, multi-species approach to canine chromosome painting. Chromosome Res, 12:825-835. [PubMed].
• Sargan D.R. (2004) IDID: inherited diseases in dogs: web-based information for canine inherited disease genetics. Mamm Genome, 15:503-6. [PubMed].
• Bainbridge JWB , Mistry AJ, Schlichtenbrede F, Broderick C, Smith A, De Alwis M, Giorgiadis A, Taylor P, Squire M, Sethi C, Charteris D, Thrasher AJ, Sargan D.R., Ali RR. (2003) Stable rAAV-mediated transduction of rod and cone photoreceptors in the canine retina. Gene Therapy, 10: 1336-44. [PubMed].
• Sidjanin DJ, Lowe JK, McElwee JL, Milne BS, Phippen TM, Sargan D.R., Aguirre GD, Acland GM, Ostrander EA.(2002) Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3. Hum Mol Genet, 11:1823-33. [PubMed] [Read Full Text].