Two Variants of KIT Causing White Patterning in Stock-Type Horses

Area of Science:

• Equine genetics
• Molecular biology
• Dermatology

Background:

• Over 30 polymorphisms in the KIT Proto-Oncogene Receptor Tyrosine Kinase (KIT) gene are linked to equine white spotting patterns.
• KIT and MITF are known genetic factors contributing to white spotting in horses.

Purpose of the Study:

• To identify genetic variants associated with white spotting patterns in two horse families using a candidate-gene exon sequencing approach.
• To validate identified variants and assess their functional impact on protein sequences.

Main Methods:

• Candidate-gene exon sequencing of KIT and MITF in two horse families.
• Validation of variants in an unrelated horse population.
• In silico protein functional impact analysis using ExPASy, Protter, Phyre2, SMART, PROVEAN, SIFT, and I-TASSER.

Main Results:

• Two variants significantly associated with familial white spotting phenotypes were identified: a frameshift indel mutation in KIT (W31) in Family 1 and a non-synonymous SNP (W32) in Family 2.
• The W31 variant leads to a truncated KIT protein (115 amino acids).
• The W32 variant showed a significant association (P = 0.00271944) in an unrelated population and may subtly affect receptor function or be linked to regulatory changes.

Conclusions:

• The study identified two distinct genetic variants, W31 and W32, associated with white spotting patterns in horses.
• W31 causes a significant truncation of the KIT protein, directly impacting its function.
• W32's role in mild spotting suggests potential regulatory involvement or subtle functional changes in receptor activity.