History of Research on Cerebellar Abiotrophy (CA) - viewed 23294 times |
![]() |
![]() |
The cerebellum (Latin for little brain) is a region of the brain that plays an important role in the integration of sensory perception, coordination and motor control. In order to coordinate motor control, there are many neural pathways linking the cerebellum with the cerebral motor cortex (which sends information to the muscles causing them to move) and the spinocerebellar tract (which provides proprioceptive feedback on the position of the body in space). The cerebellum integrates these pathways, like a train conductor, using the constant feedback on body position to fine-tune motor movements. It is the small section located at the base of the spinal column.
Research into cerebellar function during the early to mid 19th century was done via lesion and ablation studies in animals. Research physiologists noted that such lesions led to animals with strange movements, awkward gait, and muscular weakness. These observations and studies led to the conclusion that the cerebellum was a motor control structure. The neuron’s place as a primary fuctional unit of the nervous stystem was first recognized in the early 20th century through the work of the Spanish anatomist, Santiago Ramon y Cajal (1852 -1934). Caja proposed that neurons were discrete cells that commucated with each other via specialized junctions or spaces between cells. This became known as the neuron doctrine, one of the central tenets of modern neuroscience.
Under the name of Cerebellar Hypoplasia, Max T. Sponseller based his paper on 21 cases reported from California, Maryland, Michigan, Minnesota and Great Britain, indicating that the condition was possibly genetic and due to inbreeding. As more information was found, more research studies were published with a flurry of papers presented during the 70’s and 80s. Both England and Australia were searching the cause of sheep staggers and the similar clinical signs in Arabian horses and their derivatives. What J.R.M. Innes and Sponseller had started, was followed by publications in the Veterinary Record by Palmer AC, Blakemore WF, Cook WR, Platt H, Whitwell KE: “Cerebellar hypoplasia and degeneration in the young Arab horse: clinical and neuropathological features.”1973 Jul 21; 93(3):62-6. PMID: 4748678. Palmer et al published their studies on 9 cases in Great Britain from 1968-1972, with illustrations and resumes in French and German, indicating once again that this condition was genetic but not necessarily from inbreeding per se but how 'repetitive' close inbreeding occurred. As of 1974, Australia and New Zealand had sufficient cases of a degenerative neurological disorder to implement the exhaustive research of J.D. Baird and C.D. Mackenzie into Cerebellar Hypoplasia as it was still being called then. Of several studies, their most in depth was published in the Australian Veterinarian Journal: Aust Vet J. 1974 Jan;50(1):25-8. “Cerebellar hypoplasia and degeneration in part-Arab horses”. Baird JD, Mackenzie CD. PMID: 4819469 [PubMed - indexed for MEDLINE]. In fact as of the year 2000, Baird’s works were about the only available resources for Equine Cerebellar Hypoplasia or Cerebellar Abiotrophy available on line.
1990 also saw the development and use of the first single nucleotide polymorphisms (SNPs) as a data base sequencing aide, distinguishing between individuals and species, genetic analysis of disease and complex traits, assessment of linkage disequilibrium (LD), haplotype map generation, pharmacogenomics, etc. These initial sequencing machines were extremely costly, not only to build but also to run. Many improvements have been made over the last two decades with the result that the Horse Genome Project finally has been completed in 2007 enabling genetic research to surge forward.
Leah S. Ruth, Melissa M. Locke and Ann T. Bowling presented a report of a planned study at the January 2001 Plant & Animal Genome Conference to be based on tissue samples of the DNA of 30 of the original 48 family members of the mid 80s test herd. Their mtDNA research at that time to show the matrilineal diversity for Arabian horses in the United States, using 62 tested horses, showed the existence of 34 individual mare lines acquired primarily in the mid to late 19th century from nomadic Bedouin tribes. They intended to use this information to intensify their studies on Cerebellar Abiotrophy. As of 2005 Cecelia Penedo, Leah S. Brault and Thomas R. Famula have been developing markers at UC Davis. Caroline Hahn of the University of Edinburgh published her research in January 2006, and further studies have been done in Spain by A. Blanco published in August of the same year.
Leah S. Brault specializes in mapping and identification of the gene responsible for Equine Cerebellar Abiotrophy in Arabian horses; coat color genes in horses; equine genome mapping. The CA test looks for a specific set of alleles that are co-inherited with CA which can be used as a diagnostic tool to identify affected foals and also animals that are potential carriers of the disease. Breeders who wish to test their horses before breeding may use the CA test in order to avoid breeding two suspected carriers together. Click HERE for more information on how to order tests. |