Exon skipping in the KIT gene causes a Sabino spotting pattern in horses.

The research investigates the genetic origin of the Sabino spotting pattern in horses, identifying a specific genetic variation or single nucleotide polymorphism (SNP) in the KIT gene that leads to the skipping of exon 17 and subsequent Sabino 1 phenotype.

Background

• Sabino spotting is a particular pattern of white patches observed in horses, typically present on the face, lower legs, or belly, along with dispersed white hairs around the midsection.
• The researchers sought to identify the genetic basis for this pattern, inspired by similar phenotypes seen in humans and pigs associated with the KIT gene.
• The Sabino 1 pattern was, therefore, the primary focus of this investigation, symbolized by alleles SB1 and sb1.

Methodology

• Testing involved characterizing transcripts of KIT through reverse transcriptase polymerase chain reaction (RT-PCR) and sequencing cDNA (complementary DNA).
• Horses of various genotypes relating to Sabino 1 (SB1/SB1, SB1/sb1, and sb1/sb1) were included in the study.
• An examination of genomic DNA sequencing of KIT was undertaken to detect any changes or polymorphisms.

Findings

• The researchers found that horses with the Sabino 1 trait produce a different splice variant of the KIT gene that doesn’t include exon 17.
• The KIT gene in these horses featured an SNP caused by a base substitution of T with A in intron 16, 1037 bases after exon 16, named as KI16+1037A.
• This genetic change removed a MnlI restriction site, critical for genetic research and sequencing, hence allowing researchers to specifically identify individuals with the Sabino 1 base change.
• There was observed complete linkage between this SNP and Sabino 1 in a particular breed of horses – Tennessee Walking Horses.

Implications

• All horses homozygous for this SNP were white, and those with one copy of this SNP displayed the Sabino 1 phenotype or were multipatterned. Some appeared white due to the stacking effect of white spotting patterns.
• However, some horses featuring other Sabino-type patterns did not bear this SNP, hinting at the significant genetic heterogeneity in generating these patterns.
• The findings suggest the SNP within intron 16 is responsible for the skipping of exon 17 causing the Sabino 1 phenotype and that the Sabino and White phenotypes are not generated via only this mechanism.
• Also, horses homozygous for SB1 tend to exhibit an almost completely white phenotype.