Identification of the porcine homologous of human disease causing trinucleotide repeat sequences.

Expansion in the repeat number of intragenic trinucleotide repeats (TNRs) is associated with a variety of inherited human neurodegenerative diseases. To study the composition of TNRs in a mammalian species representing an evolutionary intermediate between humans and rodents, we describe in this paper the identification of porcine noncoding and polyglutamine-encoding TNR regions and the comparison to the homologous TNRs from human, chimpanzee, dog, opossum, rat, and mouse. Several of the porcine TNR regions are highly polymorphic both within and between different breeds. The TNR regions are more conserved in terms of repeat length between humans and pigs than between humans and rodents suggesting that TNR lengths could be implicated in mammalian evolution. The TNRs in the FMR2, SCA6, SCA12, and Huntingtin genes are comparable in length to alleles naturally occurring in humans, and also in FMR1, a long uninterrupted CGG TNR was identified. Most strikingly, we identified a Huntingtin allele with 21 uninterrupted CAG repeats encoding a stretch of 24 polyglutamines. Examination of this particular Huntingtin TNR in 349 porcine offspring showed stable transmission. The presence in the porcine genome of TNRs within genes that, in humans, can undergo pathogenic expansions support the usage of the pig as an alternative animal model for studies of TNR evolution, stability, and functional properties.