Equine Genetic Projects of Dr. Rebecca Bellone

Dr. Bellone and Horse

Horse head illustrationDr. 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 ocular disorders, pigmentation, 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, including Equine Recurrent Uveitis (ERU) in the Appaloosa and related breeds.

Her research efforts have identified the mutations that cause several other pigmentation traits in horses and her team recently identified the first known genetic risk factor for ocular squamous cell carcinoma in horses.

Dr. Rebecca Bellone with two of her graduate students and an appaloosa horse
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 | People | Publications

PROJECTS

Dr. Bellone’s research team, which involves collaboration with other scientists 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.

Join a Study

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

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 liver chestnut, calico spotting, rabicano, and other white spotting patterns not explained by known mutations. Recently we identified two variants that cause a distinctive iris color in Puerto Rican Paso Fino, known as Tiger Eye and the dilution mutation causing the mushroom coat color in Shetland ponies.

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 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. Subsequent research determined that this variant is also a risk factor in Belgian Horses and identified a Rocky Mountain horse affected with ocular SCC that was also homozygous for this variant. 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.

Distichiasis
Distichiasis is a condition where eye lashes grow abnormally from the inner margins of the eyelid. These aberrant lashes can cause corneal ulcers and result in vision loss. While rare in horses, the Friesian breed appears to have a breed predilection for this disease suggesting a genetic mechanism is likely responsible.

 

TEAM

Dr. Bellone Lab Members

 

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

 

Current Team Members


Nicole Kingsley Profile Photo

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 Profile Photo

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 Profile Photo

Jocelyn Tanaka completed a Masters in Animal Biology at UC Davis in December 2019. As part of her thesis she identified the genetic cause for the mushroom dilution in Shetland ponies and studied the genetic mechanisms of several other pigmentation traits in horses and donkeys. She currently is a research technician at the Veterinary Genetics Laboratory assisting in a test development and research sections.


Erin Hisey Profile Photo

Erin Hisey is a first year veterinary student at UC Davis. She began working in the equine research section as a second year Animal Science undergraduate student and is currently investigating the genetic mechanisms for distichiasis in Friesian horses.


Izzie Hack

Izzie Hack is an Animal Biology undergraduate student at UC Davis. She joined the Bellone laboratory during her third year, and is currently working on projects researching the genetics of Congenital Stationary Night Blindness (CSNB) in Tennessee Walking Horses and Equine Recurrent Uveitis (ERU) in Icelandic horses.


Elizabeth Esdaile

Elizabeth Esdaile is a Masters student in the Animal Biology Graduate group. She is currently studying the genetics of several coat color traits in horses as well as genetic diversity within and among horse breeds under the mentorship of Dr. Bellone and Dr. Avila.


Alexandra Grillos

Alexandra Grillos is a second year veterinary student at UC Davis, and received her undergraduate degree from Cal Poly San Luis Obispo. She is currently working on a project that investigates the genetics of early pregnancy loss in Thoroughbreds. This project includes a collaboration between the Veterinary Genetics Laboratory and the Royal Veterinary College in London, UK.


 

Juliana Mun (profile coming soon)

 

Past Team Members


Margo Crausaz Profile Photo

Margo Crausaz is currently working towards her veterinary degree at the University of Edinburgh's Royal (Dick) School of Veterinary Studies. She joined the laboratory during the end of her last year as a UC Davis undergraduate and stayed on for the following year prior to moving to Scotland. Her work contributed to data collection and analysis of the genetics of squamous cell carcinoma in multiple breeds of horses.


Helena Rockwell Profile Photo

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. Currently she is a first year medical student at University of California, San Diego.


Moriel Singer-Berk Profile Photo

Moriel Singer-Berk completed a Masters in Animal Biology at UC Davis in December 2018. As part of her thesis, she investigated risk factors for squamous cell carcinoma in multiple horse breeds. She currently is a clinical genomic variant curator at the Broad Institute.


Jiayin Liu Profile Photo

Jiayin Liu is currently in her last 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.


Maura Mack Profile Photo

Maura Mack is currently in her third year of Veterinary School at Colorado State. She joined the laboratory as a UC Davis 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.


Savanna Vig Profile Photo

Dr. Savanna Vig completed her veterinary degree at UC-Davis in 2017. 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. She currently is a practicing veterinarian at VCA Loomis Basin Veterinary Clinic


Coral Alberi Profile Photo

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 Profile Photo

Alyssa Atilano is currently working towards her veterinary degree from the UC Davis School of Veterinary Medicine. 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

  • View Publications (last 5 years)
  • Sandmeyer, L. S., Kingsley, N. B., Walder, C., Archer, S., Leis, M. L., Bellone, R. R., & Bauer, B. S. (2020). Risk factors for equine recurrent uveitis in a population of Appaloosa horses in western Canada. Veterinary Ophthalmology, 23(3), 515-525. doi: 10.1111/vop.12749

    Magdesian, K.G., Tanaka, J., & Bellone, R.R. (2020). A De Novo MITF Deletion Explains a Novel Splashed White Phenotype in an American Paint Horse. Journal of Heredity, 111(3), 287-293. doi: 10.1093/jhered/esaa009

    Kingsley, N.B., Kern, C., Creppe, C., Hales, E.N., Zhou, H., Kalbfleisch, T.S., MacLeod, J.N., Petersen, J.L., Finno, C.J., & Bellone, R.R. (2020). Functionally Annotating Regulatory Elements in the Equine Genome Using Histone Mark ChIP-Seq. Genes, 11(1), 3. doi: 10.3390/genes11010003

    Rockwell, H., Mack, M., Famula, T., Sandmeyer, L., Bauer, B., Dwyer, A., Lassaline, M., Beeson, S., Archer, S., McCue, M., & Bellone, R.R. (2020). Genetic investigation of equine recurrent uveitis in Appaloosa horses. Animal Genetics, 51(1), 111-116. doi: 10.1111/age.12883

    Saldinger, L.K., Nelson, S.G., Bellone, R.R., Lassaline, M., Mack, M., Walker, N.J., & Borjesson, D.L. (2019). Horses with equine recurrent uveitis have an activated CD4+ T‐cell phenotype that can be modulated by mesenchymal stem cells in vitro. Veterinary Ophthalmology, 2019; 00: 1-11. https://doi.org/10.1111/vop.12704

    Raudsepp, T., Finno, C.J., Bellone, R.R. & Petersen, J.L. (2019). Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post‐genome era. Animal Genetics, 50(2), 569-597. doi: 10.1111/age.12857

    Tanaka, J., Leeb, T., Rushton, J., Famula, T.R., Mack, M., Jagannathan, V., Flury, C., Bachmann, I., Eberth, J., McDonnell, S.M., Penedo, M.C.T., & Bellone, R.R. (2019). Frameshift Variant in MFSD12 Explains the Mushroom Coat Color Dilution in Shetland Ponies. Genes, 10, 826. doi: 10.3390/genes10100826

    Singer-Berk, M., Knickelbein, K.E., Lounsberry, Z.T., Crausaz, M., Vig, S., Joshi, N., Britton, M., Settles, M.L., Reilly, C.N., Bentley, E., Nunnery, C., Dwyer, A., Lassaline, M.E. & Bellone, R.R. (2019). Additional Evidence for DDB2 T338M as a genetic risk factor for ocular squamous cell carcinoma in horses. International Journal of Genomics, Vol. 2019, Article ID 3610965, 10 pages. doi: 10.1155/2019/3610965.

    Bellone, R.R., Ocampo, N.R., Hughes, S.S., Le, V., Arthur, R., Finno, C.J. & Penedo, M.C.T. (2019). Warmblood fragile foal syndrome type 1 mutation (PLOD1 c.2032G>A) is not associated with catastrophic breakdown and has a low allele frequency in the Thoroughbred breed. Equine Veterinary Journal, 52, 411-414. doi: 10.1111/evj.13182

    Knickelbein, K.E., Lassaline, M.E., Singer-Berk, M., Reilly, C.M., Clode, A.B., Famula, T.R., Michau T.M., & Bellone, R.R. (2019). A missense mutation in damage-specific DNA binding protein 2 is a genetic risk factor for ocular squamous cell carcinoma in Belgian horses. Equine Veterinary Journal, 52(1), 34-40. doi: 10.1111/evj.13116

    Knickelbein, K.E., Lassaline, M., Bellone, R.R. (2019). Limbal squamous cell carcinoma in a Rocky Mountain Horse: Case report and investigation of genetic contribution. Veterinary Ophthalmology, 22(2), 201-205. doi: 10.1111/vop.12612

    Cranford, T.L., Velazquez, K.T., Enos, R.T., Sougiannis, A.T., Bader, J.E., Carsons, M.S., Bellone, R.R., Charzistamou, I., Nagarkatti, M., Mruphy, E.A. (2019). Effects of high fat diet-induced obesity on mammary tumorigenesis in the PyMT/MMTV murine model. Cancer Biology & Therapy, 20(4), 487-496. doi: 10.1080/15384047.2018.1537574

    Kalbfleisch, T.S., Rice, E.S., DePriest, M.S., Jr., Walenz, B.P., Hestand, M.S., Vermeesch, J.R., Connell, B.L., Fiddes, I.T., Vershinina, A.O., Saremi, N.F., Petersen, J.L., Finno, C.J., Bellone, R.R., McCue, M.E., Brooks, S.A., Bailey, E., Orlando, L., Green, R.E., Miller, D.C., Antczak, D.F., & MacLeod, J.N. (2018). Improved reference genome for the domestic horse increases assembly contiguity and composition. Communications Biology 1:197. doi: 10.1038/s42003-018-0199-z

    Alberi, C., Hisey, E., Lassaline, M., Atilano, A., Kalbfleisch, T., Stoppini, R., Hermans, H., Back, W., Mienaltowski, M.J., & Bellone, R.R. (2018). Ruling out BGN variants as simple X-linked causative mutations for bilateral corneal stromal loss in Friesian horses. Animal Genetics, 49(6), 656-657. doi: 10.1111/age.12726

    Burns, E.N., Bordbari, M., Mienaltowski, M., Affolter, V., Barro, M.V., Gianino, F., Gianino, G., Giulotto, E., Kalbfleisch, T.S., Katzman, S.A., Lassaline, M., Leeb, T., Mack, M., Muller, E.J., MacLeod, J.N., Ming-Whitfield, B., Ramirez Alanis, C., Raudsepp, T., Scott, E., Vig, S., Zhou, H., Petersen, J., Bellone, R.R., & Finno, C.J. (2018). Generation of an equine biobank to be used for Functional Annotation of Animal Genomes project. Animal Genetics, 49(6), 564-570. doi: 10.1111/age.12717

    Singer-Berk, M., Knickelbein, K.E., Vig, S., Liu, J., Bentley, E., Nunnery, C., Reilly, C., Dwyer, A., Drögemüller, C Unger, L., Gerber, V., Lassaline, M., & Bellone, R.R. (2018). Genetic risk for squamous cell carcinoma of the nictitating membrane parallels that of the limbus in Haflinger horses. Animal Genetics, 49(5), 457-460. doi: 10.1111/age.12695

    Mack, M., Kowalski, E., Grahn, R., Bras, D., Penedo, M. C. T., & Bellone, R. (2017). Two Variants in SLC24A5 Are 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., & Bellone, R. R. (2016). Variant in the RFWD3gene associated with PATN1, 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

BOOKS AND BOOK CHAPTERS

  • View Books (last 5 years)
  • Bellone, R.R. (2017) Chapter 7: Genetic testing as a tool to identify horses with or at risk for ocular disorders. In: Veterinary Clinics of North America: Equine Practice on Equine Ophthalmology Ed: Mary Lassaline Philadelphia, PA Elsevier, Inc, pp 626-645.

    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, pp 545-566.

Bellone Lab Team

 

Top banner image courtesy of Katy Robertson