2004, Texas A&M University
Research Focus Areas
My laboratory studies canine inherited diseases to 1) improve the health and quality of life for dogs and 2) use the dog as a model to better understand the genetics underlying mammalian hereditary diseases. Dog breeds are homogenous populations that exhibit unrivaled phenotypic diversity and present unique opportunities for analysis of both simple and complex traits. Specifically, my research concerns the developmental genetics of canine pigmentation patterns. One focus of this work is merle, a semi-dominant coat pattern characterized by patches of full pigment on a dilute background (Figure 1). Dogs homozygous for merle exhibit auditory and ocular anomalies that are phenotypically similar to those of Waardenburg Syndrome type 2 in the human. Another focus is harlequin coat patterning, a bigenic trait resulting from the interaction of the harlequin locus and the merle locus. Harlequin is a dominant modifier of merle that removes the dilute pigment, leaving the background white (Figure 1). Another facet of my research concerns dermatomyositis, an inflammatory disease of the skin and muscle that is found predominantly in Collies and Shetland Sheepdogs. Finally, my laboratory is investigating the genetic basis of two prominent diseases of the German Shepherd Dog: pancreatic acinar atrophy, a disorder that causes exocrine pancreatic insufficiency (Figure 2) and megaesophagus, a congenital dysfunction of the esophagus that causes neonatal mortality. To dissect the genetic bases for these disorders my laboratory employs various tools to carry out genome-wide association studies. A major goal of our research is to develop commercially available tests to allow for early detection of disease and enable breeders to eliminate affected and carrier dogs from breeding programs.
Figure 1. Great Dane puppies with three different coat patterns (from left to right): merle, harlequin, and solid. Solid-coated puppies may or may not carry harlequin.
Figure 2. A German Shepherd Dog with exocrine pancreatic insufficiency.
National Institutes of Health
Naturally Occurring Dog Model for Juvenile Dermatomyositis
Collie Health Foundation
Collie Whole-genome Sequence and Genome-wide Association Studies
Great Dane Club of America Charitable Trust
Great Dane Whole-genome Sequence Assembly
Clark, L.A. and A.N. Starr-Moss (2013). Genetics and Genomics of the Domestic Dog. In: Animal Molecular and Quantitative Genetics. Ed: H. Khatib. Hoboken, New Jersey. Wiley-Blackwell. (in press)
Tsai, K.L., A.N. Starr-Moss, G.M. Venkataraman, C. Robinson, L.j. Kennedy, J.M. Steiner, and L.A. CLark (2013). Alleles of the major histocompatibility complex play a role in the pathogenesis of pancreatic acinar atrophy in dogs. Immunogenetics (in press).
Noorai, R.E., N.H. Freese, L.M. Wright, S.C. Chapman* and L.A. Clark* (2012). Genome-wide Association Mapping and Identification of Candidate Genes for Rumpless and Ear-tufted Traits of the Araucana Chicken. PLoS ONE 7(7):e40974.
Clark, L.A. and M.L. Cox (2012). Current status of genetic studies of exocrine pancreatic insufficiency in dogs. Topics in Companion Animal Medicine 10.1053/j.tcam.2012.04.001.
Tsai, K.L., R.E. Noorai, A.N. Starr-Moss, P. Quignon, C.J. Rinz, E.A. Ostrander, J.M. Steiner, K.E. Murphy and L.A. Clark (2012). Genome-wide association studies for multiple diseases of the German Shepherd Dog. Mammalian Genome 23:203-211.
Gill, J.L., K.L. Tsai, C. Krey, R.E. Noorai, J.F. Vanbellinghen, L.S. Garosl, G.D. Shelton, L.A. Clark* and R.J. Harvey* (2012). A canine BCAN microdeletion associated with episodic falling syndrome. Neurobiology of Disease 45 (1):130-136.
Clark, L.A., K.L. Tsai, A.N. Starr, K.L. Nowend and K.E. Murphy (2011). A missense mutation in the 20S proteasome B2 subunit of Great Danes having harlequin coat patterning. Genomics 97: 244-248.
Spadafora, D., E.C. Hawkins, K.E. Murphy, L.A. Clark and S. T. Ballard (2010). Naturally-occurring mutations in the canine CFTR gene. Physiological Genomics 42: 480-485.
Strain, G, L.A. Clark, J.M. Wahl, A. Turner and K.E. Murphy (2009). Prevalence of deafness in dogs heterozygous or homozygous for the merle allele. Journal of Veterinary Internal Medicine 23: 282-286.
Clark, L.A., J.M. Wahl, C.A. Rees, G.M. Strain, E.J. Cargill, S.L. Vanderlip and K.E. Murphy (2008). Canine SINEs and their effects on phenotypes of the domestic dog. In: Genomics of Disease. Eds: J.P.Gustafson, J. Taylor, G. Stacey. New York, New York. Springer Science+Business Media, LLC: 79-88.
Wahl, J.M., S. Herbst, L.A. Clark, K.L. Tsai and K.E. Murphy (2008). A review of hereditary diseases of the German Shepherd Dog. Journal of Veterinary Behavior 3 (6): 255-65.
Clark, L.A., A.N. Starr, K.L. Tsai and K.E. Murphy (2008). Genome-wide linkage scan localizes the harlequin locus in the Great Dane to chromosome 9. Gene 418 (1-2): 49-52.
Clark, L.A., K.L. Tsai and K.E. Murphy (2008). Alleles of DLA-DRB1 are not unique in German Shepherd Dogs having degenerative myelopathy. Animal Genetics 39 (3): 332.
Wahl, J.M., L.A. Clark, O. Skalli, A. Ambrus, C.A. Rees, J.L. Mansell and K.E. Murphy (2008). Analysis of gene transcript profiling and immunobiology in Shetland sheepdogs with dermatomyositis. Veterinary Dermatology 19 (2): 52-58.
Kerns, J., E.J. Cargill, L.A. Clark, S. Candille, T. Berryere, M. Olivier, G. Lust, S. Schmutz, K. Murphy and G. Barsh (2007). Linkage and segregation analyses of black and brindle coat color in domestic dogs. Genetics 176 (3): 1679-1689.
Tsai K.L., L.A. Clark and K.E. Murphy (2007). Understanding hereditary diseases using the dog and human as companion model systems. Mammalian Genome 18 (6-7): 444-451.Clark, L.A., J.M. Wahl, C.A. Rees and K.E. Murphy (2006). Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog. Proceedings of the National Academy of Sciences 103: 1376-1381. (work highlighted by: a. accompanying Commentary; b. mention in This Week in PNAS and; c. selection of an image for the cover).