Elimination of INPP4A and SLC5A7 as candidate genes for congenital progressive ataxia and spastic paresis in pigs.

The gene causing congenital progressive ataxia and spastic paresis (CPA) in Large White piglets remains unknown. This lethal neuropathy manifests shortly after birth, and is inherited as a single autosomal recessive allele cosegregating with the microsatellite SW9021 on SSC3, which approximately corresponds to position 90–110 Mb on HSA2.2 INPP4A (inositol polyphosphate-4-phosphatase, type 1) and SLC5A7 (solute carrier family 5, choline transporter, member 7) are attractive positional and functional candidates as they map within this region and are also involved in diseases with similar phenotypes. A 1-bp deletion in INPP4A causes the weeble (wbl) mutation in mice, a disorder characterized by severe locomotor instability and ataxia.3 SLC5A7 encodes a transmembrane transporter in neurons; a missense mutation in a gene of the same family in cattle (SLC35A3) has been shown to cause complex vertebral malformations and locomotor instability.