Development and Implementation of a Simple KASP Genotyping Test for Identifying Tay-Sachs Disease Carriers in Jacobs Sheep

Tay-Sachs disease (TSD) is a rare autosomal recessive neurodegenerative disorder affecting the central nervous system and is a direct response to a point mutation in the gene β-N-acetylhexosaminidase A (HEX A). Clinical presentation begins in infancy with startle response, development delay, before eventual progression to a vegetative state. Jacobs sheep are thus far the only identified breed of Ovis aries known to carry and present similar pathology to humans. The Jacobs Sheep Society (JSS), have been monitoring Tay-Sachs disease in the UK since 2011.  Working with the veterinary community, researchers at Cambridge University, DEFRA Animal Health and LGC Ltd the JSS has funded the creation of a UK test to identify Tay-Sachs in Jacobs sheep. The test is voluntary and is now available to members who wish to test their stock. Here we present the design and validation of a simple KASP genotyping assay which detects the G to C transition at position 1330 of the hexa gene which induces the amino acid change Gly444 to Arg, the known disease-causing mutation. Sample set comprised 34 sheep from UK flocks, with 6 previously determined and well characterized controls, including 2 heterozygous carriers and 2 samples collected from Tay-Sachs presenting homozygous lambs. The hope is to identify Tay-Sachs carriers within UK flocks and to control the occurrence of the disease.