[논문]Whole-Genome SNP Association in the Horse: Identification of a Deletion in Myosin Va Responsible for Lavender Foal Syndrome

Brooks, Samantha A.; Gabreski, Nicole; Miller, Donald; Brisbin, Abra; Brown, Helen E.; Streeter, Cassandra; Mezey, Jason; Cook, Deborah; Antczak, Douglas F.

doi:10.1371/journal.pgen.1000909

Whole-Genome SNP Association in the Horse: Identification of a Deletion in Myosin Va Responsible for Lavender Foal Syndrome 원문보기

PLoS genetics, v.6 no.4, 2010년, pp.e1000909 -

Brooks, Samantha A. (Department of Animal Science, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, United States of America) , Gabreski, Nicole (Department of Animal Science, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, United States of America) , Miller, Donald (Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America) , Brisbin, Abra (Department of Biological Statistics and Computational Biology, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, United States of America) , Brown, Helen E. (Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America) , Streeter, Cassandra (Department of Animal Science, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, United States of America) , Mezey, Jason (Department of Biological Statistics and Computational Biology, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, United State) , Cook, Deborah , Antczak, Douglas F.

Abstract ▼ AI-Helper

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.Author SummaryGenetic disorders affect many domesticated species, including the horse. In this study we have focused on Lavender Foal Syndrome, a seizure disorder that leads to suffering and death in foals soon after birth. A recessively inherited disorder, its occurrence is often unpredictable and difficult for horse breeders to avoid without a diagnostic test for carrier status. The recent completion of the horse genome sequence has provided new tools for mapping traits with unprecedented resolution and power. We have applied one such tool, the Equine SNP50 genotyping chip, to a small sample set from horses affected with Lavender Foal Syndrome. A single genetic location associated with the disorder was rapidly identified using this approach. Subsequent sequencing of functional candidate genes in this location revealed a single base deletion that likely causes Lavender Foal Syndrome. From a practical standpoint, this discovery and the development of a diagnostic test for the LFS allele provides a valuable new tool for breeders seeking to avoid the disease in their foal crop. However, this work also illustrates the utility of whole-genome association studies in the horse.

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Whole-Genome SNP Association in the Horse: Identification of a Deletion in Myosin Va Responsible for Lavender Foal Syndrome 원문보기

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