UC Davis School of Veterinary Medicine Veterinary Genetics Laboratory
Equine Genetic Projects of
Dr. Rebecca Bellone
Horse head graphic with DNA strand mane

Dr. Bellone‘s research interests involve investigating traits in the horse that are economically and medically important and are useful models for other species, including humans. Most of her research focuses on the genetics of pigmentation, ocular disorders, and the connection between the two. She has long been passionate about studying the genetics of Appaloosa spotting patterns. Her research team discovered the mutation that causes these spotting patterns (known as the LP mutation for leopard complex spotting). Horses with two copies (homozygous) for this mutation have an ocular condition known as Congenital Stationary Night Blindness (CSNB) in which they are unable to see in low-light conditions. Dr. Bellone’s team also discovered that a second gene modifies the size of the white patterned area. This gene is known as PATN1, for first pattern modifier. Horses with both LP and PATN1 will have larger patterns of white than horses with just LP. Genetic testing for LP (and thus CSNB) as well as PATN1 are offered at the UC Davis Veterinary Genetics Laboratory (VGL). For more on the genetics of Appaloosa spotting patterns visit the Appaloosa Project. Currently the team is investigating other genes that contribute to variation in the size of white patterning as well as other ocular conditions in the Appaloosa and related breeds.

Dr. Rebecca Bellone with two of her graduate students (Nicole Kingsley and Moriel Singer-Berk) during a farm visit to collect samples for research. This horse has one copy of LP and therefore is not night blind. He also has one copy of PATN1 which explains his extensive white spotting pattern.

PROJECTS:

Dr. Bellone’s research team, which involves collaboration with other scientist at UC-Davis and around the globe, is investigating the genetics of several pigmentation phenotypes and/or ocular disorders, as well as contributing to efforts to better understand the functional elements of the horse genome. The primary goal of this research program is to develop tools that will assist animal breeders, owners, and clinicians with informed mating and management decisions by understanding the biological mechanisms behind several complex heritable traits.

Leopard Complex spotting: Leopard complex spotting is characterized by white depigmentation patterns observed in several breeds of horses. Akin to human generalized vitiligo, these spotting patterns in horse are bilateral and symmetrical and are characterized by the progressive loss of pigment as the horse ages. Ocular diseases have been associated with both vitiligo in humans and leopard complex spotting in horses and include congenital stationary night blindness and uveitis. The goal of this project is to further define the genes involved in the variability of the white patterning. Studying the naturally occurring model of vitiligo should unravel the biochemical mechanisms explaining both melanocyte loss and ocular issues.

Coat Color Dilution and white spotting patterns: Several other projects investigating different coat color phenotypes in horses and donkeys are currently being conducted in the laboratory. The aim is to identify novel genes involved in pigmentation for traits of interest to breeders, including the mushroom dilution, calico spotting, and rabicano. Most recently we identified two variants that cause a distinctive iris color in Puerto Rican Paso Fino, known as Tiger Eye.

Ocular Squamous Cell Carcinoma: Squamous Cell Carcinoma (SCC) is the most common tumor of the equine eye and the second most common cancer to affect the horse. Several breeds have a high occurrence of this cancer and the goal is to identify genetic risk factors that contribute to tumor development. Haflingers are among those breeds that are over-represented and the Bellone research team recently identified a recessive genetic risk variant in a protein known to repair ultraviolet radiation, namely DDB2. Horses with two copies of this variant are at greater risk of developing ocular squamous cell carcinoma than those with one or no copies. The VGL offers a test for this risk factor. Currently the team is working to better understand the functional consequences of this variant and to identify other genetic risk variants in the Haflinger and other breeds.

Equine Recurrent Uveitis: Equine Recurrent Uveitis (ERU), also known as moon blindness, is characterized by episodes of inflammation of the middle layer of the eye. This inflammation results in intraocular changes and can lead to the development of cataracts, glaucoma and eventually complete loss of vision. ERU is the most common cause of blindness in horses. The Appaloosa breed is commonly affected by this ocular condition and the focus of this project is to determine the inherited risk factors in this and other breeds.

Bilateral Corneal Stroma Loss: Bilateral corneal stromal loss (BCSL), a corneal disorder that affects Friesian horses, is characterized by bilaterally symmetrical regions of corneal stromal loss that are not typically associated with inflammation or trauma. If left untreated, the cornea can perforate and cause permanent damage leaving vision compromised. Bilateral disorders occurring in a single breed are often inherited. Thus, investigating the genetics of this disorder in the horse may inform clinical management and breeding decisions.

If you are interested in having your horse participate in one of these projects please contact Dr. Bellone

TEAM:

Dr. Bellone is equally passionate about training both graduate and undergraduate students.

Current Team Members:

Moriel Singer-Berk is a Masters student in Animal Biology at UC Davis. She is studying the functional role of the genetic risk factor for squamous cell carcinoma in Haflinger horses.

Nicole Kingsley is a Ph.D. student in the Integrative Genetics and Genomic Graduate group. She is researching the genetic underpinning of Equine Recurrent Uveitis (ERU) in Appaloosas and other breeds. She is also contributing to the Functional Annotation of Animal Genomes project (FAANG) by analyzing the Chromatin Immuno-Precipitation Sequence (ChIP-seq) data. The aim of the project is to improve the annotations for the genomes of several important agricultural species, including the horse.

Dr. Kelly Knickelbein obtained her veterinary degree from the University Of Pennsylvania School Of Veterinary Medicine in 2015. She then completed a one-year rotating internship in equine medicine and surgery followed by a one-year internship in comparative ophthalmology. Dr. Knickelbein is a veterinary ophthalmology resident at UC Davis, and under the mentorship of Drs. Mary Lassaline and Bellone, is working on projects investigating the genetics of ocular squamous cell carcinoma in multiple breeds of horses, as well as corneal disease in Friesian horses.

Jocelyn Tanaka is a fourth year Animal Science undergraduate student. She is investigating the genetics of a coat color dilution in Shetland ponies as well as studying various coat colors in donkeys.

Erin Hisey is a second year Animal Science undergraduate student. She is interested in learning about all things genetics and is currently investigating a candidate gene for distichiasis in Friesian horses. She is also contributing to several of the coat color projects in the laboratory.

Helena Rockwell is a fourth year Animal Science undergraduate with a passion for both horses and human medicine. She has been involved in several projects contributing to data collection and analysis for Equine Recurrent Uveitis and Distichia.

Past Team Members:

Jiayin Liu is currently in her second year of Veterinary School at The Ohio State. She joined the Bellone laboratory during her junior year as an Animal Science undergraduate intern. Her work contributed to the discovery of the risk variant for ocular SCC in Haflinger horses.

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Maura Mack is currently in her first year of Veterinary School at Colorado State. She joined the laboratory as an Animal Science undergraduate intern during her last year of college and stayed on for a year as a research associate before heading to veterinary school. Maura was heavily involved in several of the projects in the Bellone laboratory and presented her findings on the genetics of Equine Recurrent Uveitis in Appaloosas and the Tiger Eye phenotype in Paso Finos at several scientific meetings. Her work identified the two mutations associated with the tiger eye phenotype in Puerto Rican Paso Fino horses.

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Savanna Vig is in her final year of Veterinary School at UC-Davis. She joined the laboratory after her second year at Davis as a STAR (Students Training in Advanced Research) summer fellow. During her summer fellowship Savanna investigated a genetic risk factor for ocular SCC in multiple horse breeds.

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Coral Alberi is currently working towards her veterinary degree from the UC Davis School of Veterinary Medicine. During her undergraduate career as an Animal Science major at UC Davis, she investigated a candidate gene for Bilateral Corneal Stroma Loss in Friesian horses.

Alyssa Atilano is a recent graduate of the Animal Science program at UC-Davis. Her career goals are to become an equine practitioner specializing in reproduction. As part of her undergraduate research internship she performed pedigree analysis for several ocular disorders in horses.

PUBLICATIONS (last 5 years):

  • Mack, M., Kowalski, E., Grahn, R., Bras, D., Penedo, M. C. T., & Bellone, R. (2017). Two Variants inSLC24A5Are Associated with “Tiger-Eye” Iris Pigmentation in Puerto Rican Paso Fino Horses.G3: Genes|Genomes|Genetics,7(8), 2799–2806. doi:10.1534/g3.117.043786
  • Scott, E. Y., Mansour, T., Bellone, R. R., Brown, C. T., Mienaltowski, M. J., Penedo, M. C., Ross, P.J., Valberg, S.J., Murray, J.D.., & Finno, C. J. (2017). Identification of long non-coding RNA in the horse transcriptome.BMC Genomics,18, 511. doi:10.1186/s12864-017-3884-2.
  • Bellone, R. R., Liu, J., Petersen, J. L., Mack, M., Singer-Berk, M., Drögemüller, C., Malvick, J., Wallner, B., Brem, G., Penedo, M. C. & Lassaline, M. (2017), A missense mutation in damage-specific DNA binding protein 2 is a genetic risk factor for limbal squamous cell carcinoma in horses. International Journal of Cancer, 141 (2), 342–353. doi:10.1002/ijc.30744.
  • Mansour, T. A., Scott, E. Y., Finno, C. J., Bellone, R. R., Mienaltowski, M. J., Penedo, M. C., Ross, P.J., Valberg, S.J., Murray, J.D., & Brown, C. T. (2017). Tissue resolved, gene structure refined equine transcriptome.BMC Genomics,18, 103. doi:10.1186/s12864-016-3451-2.
  • Tuggle, C. K., Giuffra, E., White, S. N., Clarke, L., Zhou, H., Ross, P. J., Acloque, H., Reecy, J. M., Archibald, A., Bellone, R. R., Boichard, M., Chamberlain, A., Cheng, H., Crooijmans, R. P.M.A., Delany, M. E., Finno, C. J., Groenen, M. A. M., Hayes, B., Lunney, J. K., Petersen, J. L., Plastow, G. S., Schmidt, C. J., Song, J., & Watson, M. (2016), GO-FAANG meeting: a Gathering On Functional Annotation of Animal Genomes. Animal Genetics, 47 (5), 528–533. doi:10.1111/age.12466.
  • Scott, M. L., John, E. E., Bellone, R. R., Ching, J. C. H., Loewen, M. E., Sandmeyer, L. S., Forsyth, G. W. (2016). Redundant contribution of a Transient Receptor Potential cation channel Member 1 exon 11 single nucleotide polymorphism to equine congenital stationary night blindness.BMC Veterinary Research,12, 121. doi:10.1186/s12917-016-0745-1.
  • Staiger, E.A., Bellone, R.R., Sutter, N.B., & Brooks, S.A. (2016) Morphological variation in gaited horse breeds. Journal of Equine Veterinary Science, 43, 55-65. doi:10.1016/j.jevs.2016.04.096
  • Holl, H. M., Brooks, S. A., Archer, S., Brown, K., Malvick, J., Penedo, M. C. T. and Bellone, R. R. (2016), Variant in theRFWD3gene associated withPATN1, a modifier of leopard complex spotting. Animal Genetics, 47(1), 91–101. doi:10.1111/age.12375.
  • Lassaline, M., Cranford, T.L., Latimer, C.A., Bellone, R. (2015) Limbal squamous cell carcinoma in Haflinger horses. Veterinary Ophthalmology, 18 (5), 404-408 doi:10.1111/vop.12229.
  • Ludwig, A., Reissmann, M., Benecke, N., Bellone, R., Sandoval-Castellanos, E., Cieslak, M., Fortes, G.G., Morales-Muñiz, A., Hofreiter, M., & Pruvost, M. (2015) 25,000 years fluctuating selection on leopard complex spotting and congenital night blindness in horses. Philosophical Transactions of the Royal Society B: Biological Sciences, 370 (1660), 20130386. doi:10.1098/rstb.2013.0386
  • Fritz, K.L., Kaese, H.J., Valberg, S.J., Hendrickson, J.A., Rendahl, A.K., Bellone, R.R., Dynes, K.M.. Wagner, M.L., Lucio, M.A., Cuomo, F.M., Brinkmeyer-Langford, C.L., Skow, L.C., Mickelson, J.R., Rutherford, M.S., & McCue, M.E. (2014) Genetic risk factors for insidious Equine Recurrent Uveitis in Appaloosa horses. Animal Genetics, 45(3), 392-399. doi:10.1111/age.12129.
  • Promerová, M., Andersson, L.S., Juras, R., Penedo, M.C.T., Reissmann, M., Tozaki, T., Bellone, R., Dunner, S., Hořín, P., Imsland, F., Imsland, P., Mikko, S., Modrý, D., Roed, K.H., Schwochow, D., Vega-Pla, J.L., Yeganeh, H.M., Mashouf, N.Y., Cothran, E.G., Lindgren, G., & Andersson, L. (2013) World-wide frequency distribution of the ‘Gait keeper’ mutation in the DMRT3 gene. Animal Genetics, 45(2), 274–282. doi:10.1111/age.12120
  • Bellone, R.R., Holl, H., Setaluri, V., Devi, S., Maddodi, N., Archer, S., Sandmeyer, L., Ludwig, A., Foerster, D., Pruvost, M., Reissmann, M., Bortfeldt, R., Adelson, D.L., Lim, S.L., Nelson, J., Haase, B., Engensteiner, M., Leeb, T., Forsyth, G., Mienaltowski, M.J., Mahadevan, P., Hofreiter, M., Paijmans, J. L.A., Gonzalez-Fortes, G., Grahn, B., & Brooks, S.A. (2013) Evidence for a Retroviral Insertion in TRPM1 as the Cause of Congenital Stationary Night Blindness and Leopard Complex Spotting in the Horse. PLoS ONE, 8(10), e78280 doi:10.1371/journal.pone.0078280.
  • Haase, B., Signer-Hasler, H., Binns, M.M., Obexer-Ruff, G., Hauswirth, R., Bellone, R., Burger, D., Rieder, S., Wade, C., & Leeb, T. (2013) Accumulating mutations in series of haplotypes at the KIT and MITF loci are major determinants of white markings in Franches-Montagnes horses. PLoS ONE, 8(9):e75071. doi:10.1371/journal.pone.0075071.
  • Hauswirth, R., Jude, R., Haase, B., Bellone, R.R., Archer, S., Holl, H., Brooks, S.A., Tozaki, T., Penedo, M.C.T., Rieder, S., & Leeb, T. (2013) Novel variants in the KIT and PAX3 gene in horses with white spotted coat colour phenotypes. Animal Genetics, 44(6):763-765. doi:10.1111/age.12057.
  • Makvandi-Nejad, S., Hoffman, G.E., Allen, J.J., Chu, E., Gu, E., Chandler, A.M., Loredo, A.I., Bellone, R.R., Mezey, J.G., Brooks, S.A., & Sutter, N.B. (2012) Four Loci Explain 83% of Size Variation in the Horse. PLoS One, 7(7):e39929. doi:10.1371/journal.pone.0039929.
  • Sandmeyer, L. S., Bellone, R.R., Archer, S., Bauer, B. S., Nelson, J., Forsyth, G. & Grahn, B. H. (2012) Congenital stationary night blindness is associated with the leopard complex in the miniature horse. Veterinary Ophthalmology, 15(1),18-22. doi:10.1111/j.1463-5224.2011.00903.x.

BOOKS AND BOOK CHAPTERS (last 5 years):

  • Sponenberg, D.P. and Bellone, R.R. (2017) Equine Color Genetics. 4th Edition Ames, IA: Iowa State University Press. ISBN: 978-1-119-13058-1.
  • Sandmeyer, L. & Bellone, R. (2017) Chapter 13: Inherited Ocular Disorders. In: Equine Ophthalmology, third edition Ed: Brian Gilger Ames, IA: Wiley Blackwell, pp545-566.
  • Brooks, S.A., & Bellone, R.R. (2013) Chapter 9: Coat color genomics In: Equine Genomics Ed: Bhanu Chowdhary Ames, IA: Wiley Blackwell, pp 143-153.

Veterinary Genetics Laboratory, Tel 530-752-2211, Email VGL