Mapping of equine cerebellar abiotrophy to ECA2 and identification of a potential causative mutation affecting expression of MUTYH.
Abstract: 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.
Copyright © 2010 Elsevier Inc. All rights reserved.
Publication Date: 2010-11-30 PubMed ID: 21126570DOI: 10.1016/j.ygeno.2010.11.006Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article explores a neurological disease called Equine Cerebellar Abiotrophy (CA) that is common in Arabian horses. The scientists have found a linkage between the disease phenotype and a particular genetic marker, and a potential causative mutation affecting the expression of a certain gene known as MUTYH.
Study of Equine Cerebellar Abiotrophy (CA)
- This research primarily focuses on understanding Equine Cerebellar Abiotrophy (CA), a progressive neurological condition impacting Arabian horses. It leads to the degeneration of Purkinje cells, vital neurons present in the cerebellum, responsible for basic functions like maintaining balance and motor control.
- In horses affected by this disease, symptoms such as ataxia (a lack of muscle coordination), head tremors, and a disturbed balance equilibrium are frequently observed.
Linkage to genetic marker on ECA2
- Through their research, the scientists have discovered a genetic correlation between the CA phenotype (the visible symptoms and characteristics of the disease) and a microsatellite marker present on the ECA2, a horse chromosome.
- Moreover, they have identified an area of conserved homozygosity spanning approximately 142 kilobases in size. Homozygosity refers to having two identical forms of a particular gene, indicating a probable location for the disease’s gene.
Identification of mutation affecting MUTYH gene
- The research sequenced the four genes present in this identified region and they found one Single Nucleotide Polymorphism (SNP), a variation at a single site in a DNA sequence, that is exclusive to Arabian horses.
- This SNP is located in the fourth exon (a part of a gene that codes info for protein synthesis) of the TOE1 gene, and about 1200 base pairs upstream of the MUTYH gene, near a potential binding site for GATA2, a transcription factor.
- Using a technique called qPCR to analyse the cDNA from the cerebellum of the affected and unaffected horses, they inferred that the MUTYH gene’s expression is downregulated in horses with the disease. Essentially, this means that MUTYH’s usual function may be suppressed in affected horses.
- The researchers therefore suggest that this SNP could potentially disrupt the normal function of the TOE1 gene or might negatively affect the MUTYH gene’s regulation by altering the binding affinity of the transcription factor GATA2.
Cite This Article
APA
Brault LS, Cooper CA, Famula TR, Murray JD, Penedo MC.
(2010).
Mapping of equine cerebellar abiotrophy to ECA2 and identification of a potential causative mutation affecting expression of MUTYH.
Genomics, 97(2), 121-129.
https://doi.org/10.1016/j.ygeno.2010.11.006 Publication
Researcher Affiliations
- Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
MeSH Terms
- Animals
- Cerebellar Diseases / genetics
- Cerebellar Diseases / pathology
- Cerebellar Diseases / veterinary
- Cerebellum / metabolism
- Cerebellum / pathology
- Chromosome Mapping
- DNA Glycosylases / genetics
- GATA2 Transcription Factor / metabolism
- Gene Expression Regulation
- Genetic Association Studies
- Genetic Linkage
- Homozygote
- Horse Diseases / genetics
- Horse Diseases / pathology
- Horses / genetics
- Mutation
- Polymorphism, Single Nucleotide
- Purkinje Cells / metabolism
- Purkinje Cells / pathology
Citations
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