Analysis and mapping of CACNB4, CHRNA1, KCNJ3, SCN2A and SPG4, physiological candidate genes for porcine congenital progressive ataxia and spastic paresis.

The cause of porcine congenital progressive ataxia and spastic paresis (CPA) is unknown. This severe neuropathy manifests shortly after birth and is lethal. The disease is inherited as a single autosomal recessive allele, designated cpa. In a previous study, we demonstrated close linkage of cpa to microsatellite SW902 on porcine chromosome 3 (SSC3), which corresponds syntenically to human chromosome 2. This latter chromosome contains ion channel genes (Ca(2+), K(+) and Na(+)), a cholinergic receptor gene and the spastin (SPG4) gene, which cause human epilepsy and ataxia when mutated. We mapped porcine CACNB4, KCNJ3, SCN2A and CHRNA1 to SSC15 and SPG4 to SSC3 with the INRA-Minnesota porcine radiation hybrid panel (IMpRH) and we sequenced the entire open reading frames of CACNB4 and SPG4 without finding any differences between healthy and affected piglets. An anti-epileptic drug treatment with ethosuximide did not change the severity of the disease, and pigs with CPA did not exhibit the corticospinal tract axonal degeneration found in humans suffering from hereditary spastic paraplegia, which is associated with mutations in SPG4. For all these reasons, the hypothesis that CACNB4, CHRNA1, KCNJ3, SCN2A or SPG4 are identical with the CPA gene was rejected.

[Genomic methods for identification of traits and inherited disorders in farm animals]. / Genomik zur Identifikation von Merkmalen und Erbfehlern beim Nutztier.

In this review we demonstrate the interaction of the blueprint of an individual (the genome, genomic DNA), its phenotype and the environment. The phenotype consists of quantitative (e.g. growth, milk yield) or functional characteristics e.g. fitness, longevity, fertility and disease resistance. The latter characteristics influence the welfare of an animal substantially. As only the genetically determined part of a particular characteristic is transferred from one generation to the next, it is important to know what the genetic variants (alleles) of the parents at one or more gene loci are. New methods in molecular biology have made it possible to localize and characterize important genes which help to breed more efficient and healthy animals. The exact characterization of the phenotype is vital in identifying genes with major effects and therefore the cooperation with experts from veterinary medicine, biochemistry, and biology is indispensable. As well as an overview of available genetic tests in farm animals, we show various examples how to identify the molecular basis of a particular phenotype and how to use the results in practical breeding programs. Genetic diagnosis enables the breeder to identify undesired alleles early and hinders therefore its uncontrolled distribution in the population. In the long term this leads to a smaller number of affected animals and depending on the disease it may help to prevent animals from suffering.