Bovine CACNA1A gene and comparative analysis of the CAG repeats associated to human spinocerebellar ataxia type-6

Abstract A small expansion of a CAG repeat domain in exon 47 of the human CACNA1A gene, which codes for the pore-forming α 1A subunit of P/Q-type Ca 2+ channels, causes spinocerebellar ataxia type-6. Only the human α 1A protein has been demonstrated to contain the poly(Q) tract, although this locus has also recently been detected in ape genomes. To our knowledge, no further information has been published on other mammal species. Here, we have cloned the full-length α 1A subunit in a non-primate species, the cow. The results have made it possible to explore the exon organization of the bovine CACNA1A gene as well as the splice α 1A isoforms expressed by bovine chromaffin cells. We found a splice variant of the protein that, as in humans, also contains a polymorphic poly(Q) tract. Based on this result and using data from different Genome Databases, we performed an interspecies comparison of exon 47 and discovered that the poly(Q) tract is present in all the species studied, with the exception of primitive fish and rodents. Our results provide insight into the evolution of the CAG repeat tract at the C-terminus coding region of the CACNA1A gene.