Genetic Disorders

• severe combined immunodeficiency • cerebellar abiotrophy • lavender foal syndrome

• dwarfism • hydrocephalus

• junctional epidermolysis bullosa

• overo lethal white foal syndrome

• multiple congenital ocular anomalies

• congenital stationary night blindness

• glycogen branching ezymes disorders

• warmbloof fragile foal syndrome

• occurrence restricted to a single breed or related breeds ( in some cases, this disorder may affect only some horses within a particular breed, with the affected horses carrying a common phenotype. This is seen in the case of OLWFS, MCOA,CSNB, and LFS which occur in occur in conjuction with particular colour genotypes) • common ancestor ( HYPP and impressive, hereditary equine regional dermal asthenia and the stallion poco bueno GBED and the stallion king P- 234) = as with occurence within a breed, possibility of common usage and environmental factors must be taken into account when looking at a common ancestor • underlying biochemical aetiology ( PSSM, GBED/GSD) • similar disorder with known genetic basis occurs in other species ( SCID, dwarfism, polydactyly and HERDA)

• hereditary equine regional dermal arthenia - stock horses affected • also called hyperelastosis cutis (HC) • presents as skin peeling off, particularly over the shoulders and along the dorsal midline • usually appears during training • affected horses are typically euthanized although it is possible to extend lifespans of minimally affected horses if they are kept indoors and not subjected to any sort of physical trauma • due to a missense mutation in the cyclophilin B gene (PPIB) that regulates the three dimensional structure of collagen; which is essential for dermal integrity • mutation has been traced by a single stallion, POCO bueno (1944-1969) • first identified as a genetic disorder in 1971, causative mutation identified in 2007

• junctional epidermolysis bullosa ( draft horses, especially belgians, and ameriacan saddlebreds affected) • presents as extensive erosive ulcerative lesions on distal extremities, lips, and over joints; skin and hooves slough off • two breed - specific mutations have been identified : frameshift in LAMC2 in draft breeds causing pre mature stop codons and a large deletion in LAMA3 (american saddlebreed) - genocopies • these genes code for laminitis, involved in connecting epidermal and dermal layers of the skin • affected foals die or are euthenized

• glycogen branching enzyme disorder (also glycogen storage disorder) - effects stock horses • presents as hypoglycemic seizures, progressive muscle weakness, respiratory failures and sudden death; also identified as cause of late-term abortions • caused by nonsense mutation in glycogen branching enzyme 1 (GBE1) that disrupts glycogen metabolism • traced to King P-234 (1932-1958)

• overo lethal white foal syndrome (paint/stock horses affected) • presents as ileocolonic aganglionosis creating a fatal colic • caused by a missence mutation in the endothelin B receptor gene (EDNRB) that regulates development of neural crest cells into enteric ganglia and melanocytes

• characteristic of camarillo white, franches montagne and american white horses • sporatic appearance in thoroughbreds, american quarter horses, icelandic horses shetland ponies and arabian horses • characterized by phenotypic and allelic heterogeneity with the conidtion resulting from 27 mutations identified in the KIT gene that stimulates signaling pathways for cell growth, division, survival and migration • some of the alleles are embryonic lethals; some combinations of alleles create heterozygous lethality

• lavender foal syndrome - arabian horses effected • also called coat colour dilution lethal (CCDL) • neonates present with neurological abnormalitites such as tetanic seizures, recumbency and inability to stand along with a pale pink or lavender coat colour • causation mutation is a deletion in the myosin V gene (MYO5A) that creates a premature stop codon; myosin Va is involved in organelle transport and membrane trafficking in brain and skin

• severe combined immunodeficiency - Arabian horses affected • affected foals lack the ability to create antibodies and typically succumb to infectious disease after passive immnity acquired from the dam ceases to be effective • causative mutation is frameshift in DNA - dependent protein kinases (DNA PKcs) that play a cruicial role in formation in antibodies

• fatal immunodeficiency syndrome (fell and dale ponies effected) - also identified in gypsy vanner horses • fell pony syndrome • genocopy of SCID • immunocomprimised foals succumb to disease after passively aquired antibiodies cease to provide effective protection • causative mutation is missense mutation in sodium/ myosin -ninositol transporter (SLC5A3) necessary for erythropoiesis and formation of B and T lymphocytes

• friesian horses affected • presents as an accumulation of cerebrospinal fluid within the ventricle system of the brain that results in pre-natal or neonatal death • causative mutation in nonsense mutation ( B3GALNT2)

• naked foal syndrome (also hairless or hairlessness • akhal teke horses affected • caused by a nonsense mutation in the suppression of tumorigenicity 14 (ST14) gene that is essential for development of hair follicles • affected foals are usually euthenized although horses have been kept alive for as long as 5 years • no sun exposure and vitamine D suppliment provided

• warmblood fragile foal syndrome • warmblood breeds effected mostly • presents as neonates with fragile skin, lacerations of the mucous membranes, hyperextensible joints ; affected foals usually die or are euthenized shortly after birth - may be aborted • causative mutation is missense mutation in procollagen - lysine PLOD1 that is involved in crosslinking collagen molecules

• Hyperkalemic periodic paralysis (stock horses effected) • impressive syndrome • presents as muscle fasciculations, swaying and staggering that may progress to collapse and flaccid recumbancy ; horses can suffer laryngeal collapse and cardiac arrest • the phenotype of heterozygotes ranges from very midly or virtually unnoticeable to extremely effected ; due to an autosomal incompletely dominant mutaition • traced back to impressive 1969-1995 identified 1992

• polysaccharide storage myopathy • confers susceptibility to exertional rhabdomyolysis • autosomal dominant mode of inheritance • horses identified as having the mutation can be managed to reduced incidence and severity of episodes of exertional rhabdomyyolysis

• cerebellar abiotrophy - affects arabians and related breeds • autosomal recessive mode of inheritance • neurodegenerative disorder that manifests dats to months after birth as uncoordinated limb movement, head tremours and difficulty standing

• friesians, miniature horses, shetland ponies • mutation causing dwarfism in breed specific • all mutations thus far have identified are autosomal recessive • the different mutations in Friedan horses, miiature horses and shetland ponies are genocopies