Congenital progressive ataxia and spastic paresis, a hereditary disease in swine, maps to Chromosome 3 by linkage analysis

The congenital progressive ataxia (CPA) and spastic paresis in pigs, recently identified in Switzerland, is a disease with unknown etiology. A disease similar to CPA was described earlier by Rimaila-Paernaenen (1982). The affected animals show a neuropathic disorder, which occurs in piglets of both sexes within the first week after birth. The disease manifests itself within 1 or 2 days as a severe neuropathy, characterized by spastic gait, incoordination, and rapidly progressive ataxia in the hind limbs. Finally, the piglets remain lying down and are no longer able to support themselves. Histological examination of the central nervous system revealed no deficiency of stainable myelin nor any significant morphological changes. The disease was first observed in two litters of pigs (Table 1, matings 1 and 2), derived from two dams and one sire, all of Large White origin. The dams were cousins and not related to the sire, referring to the last two generations. Of the 23 offspring, seven (30.4%) were found to be affected and 16 (69.6%) were normal. The observed ratio of approximately 3:1 suggested that the disease may be controlled by a recessive allele. Therefore, affected animals were considered homozygous for the recessive allele (cpa/cpa), and normal animals either heterozygous for the recessive allele (CPA/cpa), or homozygous (CPA/CPA). The present studies were conducted to: (1) confirm the autosomal recessive inheritance of CPA; and (2) map the CPA phenotype to the porcine genome. Of the 16 phenotypically normal animals, two males were mated to five females, and each female produced two litters (Table 1, mating 3-12). Of the 107 descendants, 17 animals (15.9%) showed ataxia and paresis syndromes. As their condition progressively worsened, the piglets were euthanized. Their average life span was (mean plus or minus SD: 8.7 plus or minus 8.3; n = 17) days. In addition to the above offspring, nine piglets were produced from an unrelated family (Table 1, mating 13), of which three (33.3%) showed characteristics of the disease. To map the CPA phenotype, two to three highly informative microsatellite markers for each chromosome spread at intervals of about 40 cM were selected (Rohrer et al. 1996). According to conditions described in the original references (Rohrer et al. 1996), polymerase chain reaction (PCR) was carried out in a reaction volume of 25 mu l containing 100 eta g porcine genomic DNA extracted from blood, 10 mM Tris-HCl (pH 9.0), 50 mM KCl, 1.5 mM