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Home / Equine Research Bank / Anim Genet / A de novo missense mutation in KIT is responsible for domina...
Animal genetics2022; 53(4); 534-537; doi: 10.1111/age.13222

A de novo missense mutation in KIT is responsible for dominant white spotting phenotype in a Standardbred horse.

Abstract: No abstract available
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Publication Date: 2022-05-31 PubMed ID: 35641888DOI: 10.1111/age.13222Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article reveals that a unique missense mutation in the KIT gene is the cause of white spotting patterns in a New Zealand Standardbred horse. This new variant was not present in the parents, suggesting it formed de novo (newly), is detrimental to protein function, and is the third de novo white coat color variant identified in Standardbreds.

Investigations and Testing Reveal a de novo Variant

  • The Standardbred filly depicted sabino-like white patterning, which led to a series of coat color testing. These tests were aimed to determine the genetic cause of these white patterns.
  • The initial phase of testing involved commercial genotyping for known variants linked to white patterning. These variants come from several genes that cause different white patterns in horses. However, no matching patterns were found in the filly.
  • Considering that multiple KIT gene variants link to similar white patterns in horses, researchers decided to analyze remaining known KIT variants. Still, they found the horse under investigation didn’t carry any of the known white patterning variants.
  • Given the lack of patterned phenotypes in the filly’s parents and the negative results for known white patterning variants, researchers hypothesized that the spotting pattern seen in the filly might result from a de novo (meaning new or novel) variant in the KIT gene.

Discovering A de novo Variant in KIT Gene

  • A thorough investigation of the KIT gene coding sequence was conducted not only in the filly but also in her parents, seeking any new variants.
  • Amplicon sequencing showed a single missense variant in the last codon of exon 16 of the filly’s KIT gene. A missense variant is a type of mutation where a single nucleotide change results in a codon that codes for a different amino acid, potentially altering the function of the protein.
  • Sanger sequencing, a method of DNA sequencing, confirmed these findings. Both parents were found to have the homozygous reference, meaning they both presented the normal, common variant, whereas the filly had a heterozygous variant.
  • Parentage verification performed at Massey University confirmed the relationship of the filly to her parents. This result established that the detected variant arose de novo in the filly, as it wasn’t inherited from either parent.

Analyses of the Variant

  • PredictSNP – a tool for predicting the disease-relatedness and the effect of protein mutations – forecasted that the discovered KIT gene variant could significantly impede proper protein function, with an accuracy of 87%.
  • A search across 100 vertebrates highlighted that this specific location on the KIT gene is highly conserved. This means that the gene function is likely vital, and changes could have significant effects.
  • Interestingly, the same variant exists in a human European descent sample, but its clinical significance is unknown.

Proposing a New White Spotting Pattern Variant

  • As the filly is a Standardbred with sabino-like white spotting and showing unique KIT gene variant, researchers proposed to name this new variant as W33. This came after two other de novo white coat color variants identified in the breed. The first was a missense variant in the melanocyte inducing transcription factor (MITF) gene, while the second was a splice site mutation affecting exon 16 of KIT.

Cite This Article

APA
Esdaile E, Till B, Kallenberg A, Fremeux M, Bickel L, Bellone RR. (2022). A de novo missense mutation in KIT is responsible for dominant white spotting phenotype in a Standardbred horse. Anim Genet, 53(4), 534-537. https://doi.org/10.1111/age.13222

Publication

Animal genetics
ISSN: 1365-2052
NlmUniqueID: 8605704
Country: England
Language: English
Volume: 53
Issue: 4
Pages: 534-537

Researcher Affiliations

Esdaile, Elizabeth
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Till, Brad
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Kallenberg, Angelica
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Fremeux, Michelle
  • InfogeneNZ, Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand.
Bickel, Leslie
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Bellone, Rebecca R
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.

MeSH Terms

  • Animals
  • Hair Color
  • Horses / genetics
  • Mutation
  • Mutation, Missense
  • Phenotype
  • Proto-Oncogene Proteins c-kit / genetics

Grant Funding

  • UC Davis Veterinary Genetics Laboratory

References

This article includes 31 references
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Citations

This article has been cited 4 times.
  1. Avila F, Hughes SS, Magdesian KG, Penedo MCT, Bellone RR. Breed Distribution and Allele Frequencies of Base Coat Color, Dilution, and White Patterning Variants across 28 Horse Breeds. Genes (Basel) 2022 Sep 13;13(9).
    doi: 10.3390/genes13091641pubmed: 36140807google scholar: lookup
  2. Patterson Rosa L, Martin K, Vierra M, Lundquist E, Foster G, Brooks SA, Lafayette C. A KIT Variant Associated with Increased White Spotting Epistatic to MC1R Genotype in Horses (Equus caballus). Animals (Basel) 2022 Aug 2;12(15).
    doi: 10.3390/ani12151958pubmed: 35953947google scholar: lookup
  3. McFadden A, Vierra M, Robilliard H, Martin K, Brooks SA, Everts RE, Lafayette C. Population Analysis Identifies 15 Multi-Variant Dominant White Haplotypes in Horses. Animals (Basel) 2024 Feb 5;14(3).
    doi: 10.3390/ani14030517pubmed: 38338160google scholar: lookup
  4. McFadden A, Vierra M, Martin K, Brooks SA, Everts RE, Lafayette C. Spotting the Pattern: A Review on White Coat Color in the Domestic Horse. Animals (Basel) 2024 Jan 30;14(3).
    doi: 10.3390/ani14030451pubmed: 38338094google scholar: lookup
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