Mapping of equine cerebellar abiotrophy to ECA2 and identification of a potential causative mutation affecting expression of MUTYH.
Equine Cerebellar Abiotrophy (CA) is a neurological disease found in Arabian horses. CA is characterized by post-natal degeneration of the Purkinje cells of the cerebellum. Signs of CA include ataxia, head tremors, and a lack of balance equilibrium. We have discovered a linkage of the CA phenotype to a microsatellite marker on ECA2 and identified a region of conserved homozygosity spanning approximately 142 kb. Complete sequencing of the four genes in this region identified one SNP found only in Arabian horses, located in exon 4 of TOE1 and approximately 1200 base pairs upstream of MUTYH, adjacent to a possible binding site for the transcription factor GATA2. qPCR analysis of cDNA from the cerebella of affected and unaffected horses suggested that MUTYH expression is down-regulated in affected horses. This SNP may therefore have a function effect on TOE1, or a regulatory effect on MUTYH by negatively affecting the binding affinity of GATA2.
Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
Leah S
LS
Brault
Caitlin A
CA
Cooper
Thomas R
TR
Famula
James D
JD
Murray
M Cecilia T
MC
Penedo
D000818:Animals; D002526:Cerebellar Diseases / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D002874:Chromosome Mapping; D045647:DNA Glycosylases / Q000235:genetics*; D050989:GATA2 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D008040:Genetic Linkage; D006720:Homozygote; D006734:Horse Diseases / Q000235:genetics* / Q000473:pathology; D006736:Horses / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology
D050989:GATA2 Transcription Factor; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase