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.

Structural basis of cargo recognitions for class V myosins

“…Defective mutations of mammalian MyoV lead to several genetic diseases, such as GS in humans (28) and a similar syndrome in horse MyoVa (29) and microvillus inclusion disease in human MyoVb (30,31). Most of these changes are frame-shift or truncation mutations, which invariably result in truncated proteins lacking all or part of the GTD (Table S2).…”

Türkiye Arap Atı Popülasyonunda LFS ve PSSM-I Hastalıklarının Moleküler Taraması

“…One of them causes Lavender Foal Syndrome (LFS) also known as Coat Color Dilution Lethal (CCDL) which only reported in Arabian horse foals [3][4][5] and is inherited in an autosomal recessive manner [3] . Brooks et al [6] have determined the genetic mutation causing this syndrome by SNP-based whole genome association (WGA) study. According to this study, the mutation is a single base deletion of cytosine (c.4459delC) on MYO5A gene, located on ECA1 chromosome.…”

“…Diluted coat color is the decisive symptom of LFS. LFS has no cure, and thus the foals with these conditions are euthanized after birth [6] .…”

Identification and analysis of single nucleotide polymorphisms in the myosin VA (MYO5A) gene and its exclusion as the causative gene of the dilute coat colour locus in rabbit

“…This allele dilutes the black to blue (grey) and the yellow to beige coat colours of several rabbit breeds and lines (Castle, 1930;Robinson, 1958;Searle, 1968;Fox 1994). In other species, similar effects on coat colour are determined by mutations in a few genes including the myosin VA (heavy chain 12, myoxin) (MYO5A) gene, also known as dilute myosin heavy chain, non-muscle (Mercer et al, 1991;Huang et al, 1998aHuang et al, , 1998bFutaki et al, 2000;Brooks et al, 2010). MYO5A is an actin-based motor that belong to the large myosin superfamily (Mermall et al, 1998).…”