Whole-genome SNP association in the horse: identification of a deletion in myosin Va responsible for Lavender Foal Syndrome.
Abstract: Lavender Foal Syndrome (LFS) is a lethal inherited disease of horses with a suspected autosomal recessive mode of inheritance. LFS has been primarily diagnosed in a subgroup of the Arabian breed, the Egyptian Arabian horse. The condition is characterized by multiple neurological abnormalities and a dilute coat color. Candidate genes based on comparative phenotypes in mice and humans include the ras-associated protein RAB27a (RAB27A) and myosin Va (MYO5A). Here we report mapping of the locus responsible for LFS using a small set of 36 horses segregating for LFS. These horses were genotyped using a newly available single nucleotide polymorphism (SNP) chip containing 56,402 discriminatory elements. The whole genome scan identified an associated region containing these two functional candidate genes. Exon sequencing of the MYO5A gene from an affected foal revealed a single base deletion in exon 30 that changes the reading frame and introduces a premature stop codon. A PCR-based Restriction Fragment Length Polymorphism (PCR-RFLP) assay was designed and used to investigate the frequency of the mutant gene. All affected horses tested were homozygous for this mutation. Heterozygous carriers were detected in high frequency in families segregating for this trait, and the frequency of carriers in unrelated Egyptian Arabians was 10.3%. The mapping and discovery of the LFS mutation represents the first successful use of whole-genome SNP scanning in the horse for any trait. The RFLP assay can be used to assist breeders in avoiding carrier-to-carrier matings and thus in preventing the birth of affected foals.
Publication Date: 2010-04-15 PubMed ID: 20419149PubMed Central: PMC2855325DOI: 10.1371/journal.pgen.1000909Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study investigates Lavender Foal Syndrome (LFS), a fatal genetic disease in horses, particularly common in Egyptian Arabian horses. The research identifies a gene deletion in myosin Va (MYO5A) as the primary cause of LFS, using a whole-genome SNP scan – the first use of this method in equines.
Research Objectives and Strategy
- The research aimed to identify the genetic cause of Lavender Foal Syndrome (LFS), a lethal condition predominantly found in Egyptian Arabian horses and characterized by neurological abnormalities and a distinct coat color. The identified genetic cause would allow breeders to avoid carrier-to-carrier matings, and therefore prevent the birth of affected foals.
- The researchers suspected two candidate genes – the ras-associated protein RAB27a (RAB27A) and myosin Va (MYO5A) – based on similar phenotypes in mice and humans.
- To map the genetic locus responsible for LFS, the study used a set of 36 horses, which included both carriers and affected horses. This set was genotyped using a single nucleotide polymorphism (SNP) chip with 56,402 discriminatory elements for a full genome scan.
Findings and Innovations
- This study discovered upon examination of the genotype of an LFS-affected foal, that MYO5A contained a single base deletion in exon 30, which affected the gene’s reading frame and introduced a premature stop codon leading to LFS.
- A PCR-based Restriction Fragment Length Polymorphism (PCR-RFLP) assay was created to investigate the frequency of the mutant gene. The results showed that all LFS-affected horses were homozygous for this mutation (i.e., had two identical copies of the mutated gene), and carriers were common in families carrying this trait. The mutation was also found in 10.3% of unrelated Egyptian Arabian horses, suggesting a fairly high frequency of carriers in the general population.
- This research represents the first successful use of whole-genome SNP scanning in horses, which is a major step forward in equine genetics.
Implications
- The findings provide a valuable tool for breeders, as the PCR-RFLP assay can identify carriers of the LFS mutation. This in turn enables breeders to prevent carrier-to-carrier matings, and consequently, the birth of LFS-affected foals.
- Moreover, the study makes a significant contribution to the broader field of equine genetics and genetic disease prevention and can guide similar future studies in other species or for other traits.
Cite This Article
APA
Brooks SA, Gabreski N, Miller D, Brisbin A, Brown HE, Streeter C, Mezey J, Cook D, Antczak DF.
(2010).
Whole-genome SNP association in the horse: identification of a deletion in myosin Va responsible for Lavender Foal Syndrome.
PLoS Genet, 6(4), e1000909.
https://doi.org/10.1371/journal.pgen.1000909 Publication
Researcher Affiliations
- Department of Animal Science, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, United States of America. Samantha.Brooks@cornell.edu
MeSH Terms
- Animals
- Base Sequence
- Epilepsy / genetics
- Epilepsy / veterinary
- Genome
- Genotype
- Horse Diseases / genetics
- Horses / genetics
- Molecular Sequence Data
- Myosins / genetics
- Polymorphism, Single Nucleotide
- Syndrome
Conflict of Interest Statement
The authors have declared that no competing interests exist.
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