This web page was produced as an assignment for Gen677 at UW-Madison Spring 2013
What is Lavender Foal Syndrome?
Lavender Foal Syndrome (LFS), also know as Coat Color Dilution Lethal (CCDL), is a fatal neurologic disorder affecting newborn foals. The disorder has been recognized since the 1950's and is a rare but significant disease in the Arabian horse. Approximately 10% of Arabians with Egyptian bloodlines are believed to carry the genetic mutation responsible for LFS [1].
The disorder is caused by a mutation in Myosin-Va, a motor protein found in nerve cells, and causes severe neurologic problems immediately after birth [1].
Lavender Foal Syndrome is an autosomal recessive disorder [2]. Adults can carry a single copy of the mutated gene without showing any symptoms, but when two horses that are carriers are breed, one quarter of the resulting offspring are affected. |
SymptomsThe following video shows a foal suffering from LFS shortly after birth.
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Foals with LFS display several neurologic symptoms. These include [1]:
These neurologic symptoms result in the foal being unable to stand or nurse and are always fatal [1]. Affected foals are usually humanly euthanized a few days after birth. Foals with the disorder also have a diluted coat color sometimes described as silver, pewter, pale gray or lavender, resulting in the name of the disorder, "Lavender Foal Syndrome" [1]. LFS can be difficult to diagnose immediately as its symptoms are very similar to several other neonatal conditions including encephalitis and neonatal maladjustment syndrome [2]. |
MYO5a and Lavender Foal Syndrome
MYO5a is the gene that encodes the molecular motor protein Myosin Va, found on chromosome 1 in horses and chromosome 15 in humans [4,5]. This protein is predominantly expressed in the central nervous system neurons but is also found in the melanocyte pigment cells [6]. Myosin Va is responsible for the distribution of cargo organelles, such as melanosomes and secretory vesicles, within the cell [6]. The mutation resulting in Lavender Foal Syndrome affects the region of the protein where cargo organelles would normally attach [1]. This means that the cargo cannot bind to and be distributed by Myosin Va, drastically affecting the function of neurons and melanocytes [1].
Testing
There are no treatments for LFS, but thanks to the successful sequencing of the horse genome in 2009 [4], a genetic test that can identify horses that are carriers of the disease was developed at Cornell University in 2010 [7]. The ability to identify horses with a copy of the mutated gene allows breeders to make informed decisions concerning breeding horses who are carriers. The test requires a hair or blood sample and is relatively inexpensive and highly accurate [7].
Disease in Humans
Mutations in MYO5a have also been shown to cause disease in humans. Griscelli syndrome type-1, Griscelli syndrome type-3 and Elejalde disease are all linked to defects in MYO5a [8]. These diseases present with hypo-pigmentation and neurologic dysfunction including lack of coordination, mental retardation and delayed motor development [6].
References
[1] Brooks SA, Gabreski N, Miller D, Brisbin A, Brown HE, et al. (2010) Whole-Genome SNP Association in the Horse: Identification of a Deletion in Myosin VA Responsible for Lavender Foal Syndrome. PLoS Genet 6(4): e1000909. doi:10.1371/journal.pgen.1000909.
[2] Page P, Parker R, Harper C, Guthrie A, Neser J. (2006) Clinical, Clinicopathologic, Postmortem Examination Findings and Familial History of 3 Arabians with Lavender Foal Syndrome. J Vet Intern Med 20:1491-1494.
[3] National Institutes of Health. Autosomal Recessive Inheritance. Retrieved Febuary 6, 2013, from http://www.nei.nih.gov/health/biettis/more.asp
[4] Wade CM, Guilotto E, Sigurdsson S, Zoli M, et al. (2009) Genome sequence, comparative analysis, and population genetics of the domestic horse. Science 6(326) doi:10.1126/science.1178158
[5] U.S National Library of Medicine: Genetics Home Reference. MYO5a. Retrieved Febuary 5, 2013, from http://ghr.nlm.nih.gov/gene/MYO5A
[6] Miyata M, Kishimoto Y, Tanaka M, Hashimoto K, Hirashima N, Murata Y, Kano M, Takagishi Y. (2011). A Role for Myosin Va in Cerebellar Plasticity and Motor Learning: A Possible Mechanism Underlying Neurological Disorders in Myosin Va Disease. J Neurosci 31(16):6067-6078.
[7] Cornell University College of Veterinary Medicine. Genetic Testing for Lavender Foal Syndrome. Retreived Febuary 5, 2013, from http://ahdc.vet.cornell.edu/news/lfs.cfm
[8] Desnos C, Huet S, Darchen F. (2007). "Should I stay or should I go?": myosin V function in organelle trafficking. Biol Cell 99:411-423.
[2] Page P, Parker R, Harper C, Guthrie A, Neser J. (2006) Clinical, Clinicopathologic, Postmortem Examination Findings and Familial History of 3 Arabians with Lavender Foal Syndrome. J Vet Intern Med 20:1491-1494.
[3] National Institutes of Health. Autosomal Recessive Inheritance. Retrieved Febuary 6, 2013, from http://www.nei.nih.gov/health/biettis/more.asp
[4] Wade CM, Guilotto E, Sigurdsson S, Zoli M, et al. (2009) Genome sequence, comparative analysis, and population genetics of the domestic horse. Science 6(326) doi:10.1126/science.1178158
[5] U.S National Library of Medicine: Genetics Home Reference. MYO5a. Retrieved Febuary 5, 2013, from http://ghr.nlm.nih.gov/gene/MYO5A
[6] Miyata M, Kishimoto Y, Tanaka M, Hashimoto K, Hirashima N, Murata Y, Kano M, Takagishi Y. (2011). A Role for Myosin Va in Cerebellar Plasticity and Motor Learning: A Possible Mechanism Underlying Neurological Disorders in Myosin Va Disease. J Neurosci 31(16):6067-6078.
[7] Cornell University College of Veterinary Medicine. Genetic Testing for Lavender Foal Syndrome. Retreived Febuary 5, 2013, from http://ahdc.vet.cornell.edu/news/lfs.cfm
[8] Desnos C, Huet S, Darchen F. (2007). "Should I stay or should I go?": myosin V function in organelle trafficking. Biol Cell 99:411-423.
Rebecca Blackburn, [email protected], 3/7/13