Whole‐genome sequencing reveals a large deletion in the <i><scp>MITF</scp></i> gene in horses with white spotted coat colour and increased risk of deafness

Henkel, Jan; Lafayette, Christa; Brooks, Samantha A.; Martin, Katie; Rosa, Laura Patterson; Cook, Deborah; Jagannathan, Vidya; Leeb, Tosso

doi:10.1111/age.12762

Cited by 27 publications

(26 citation statements)

References 19 publications

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“…Visual inspection of the registration photographs for these 97 horses revealed that 31 possessed patterns consistent with white-spotting loci. These 31 included many phenotypes resembling those generated by alleles known but not genotyped in this cohort, including MITF*SW4 (Hauswirth et al 2013a), MITF*SW5 (Henkel et al 2019) and more than 27 other alleles at the KIT locus. We also observed among these 31 horses some well-recognized patterns with as yet unknown genetic etiology (i.e.…”

Section: Resultsmentioning

confidence: 99%

“…Of these known alleles, nine are common to and routinely tested for in the APHA population (Table 1). Others, like MITF-Splash White 4 and many of the KIT*W series alleles (at least 30 variants recorded in OMIA), are breed specific and not present in the Paint Horse, whereas some like MITF-Splash White 5 were not yet commercially available for testing at the time the study began and therefore were not examined (Hauswirth et al 2013b;Henkel et al 2019).…”

Section: Introductionmentioning

confidence: 99%

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Impact of white‐spotting alleles, including W20, on phenotype in the American Paint Horse

et al. 2020

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Summary The American Paint Horse Association (APHA) records pedigree and performance information for their breed, a stock‐type horse valued as a working farm or ranch horse and as a pleasure horse. As the name implies, the breed is also valued for its attractive white‐spotting patterns on the coat. The APHA utilizes visual inspections of photographs to determine if coat spotting exceeds threshold anatomical landmarks considered characteristic of desirable patterns. Horses with sufficient white patterning enter the ‘Regular’ registry, rather than the ‘Solid Paint‐Bred’ division, providing a threshold modeled phenotype. Genetic studies previously defined sequence variants corresponding to 35 alleles for white spotting in the horse. Here, we calculate the allele frequencies for nine common white‐spotting alleles in the American Paint Horse using a sample of 1054 registered animals. The APHA spotting phenotype is altered by additive interactions among spotting loci, and epistatically by the MC1R and ASIP genes controlling pigment production. The W20 allele within the KIT gene, independent of other known spotting alleles, was strongly associated with the APHA‐defined white‐spotting phenotype (P = 1.86 × 10−18), refuting reports that W20 acts only as a modifier of other underlying white‐spotting patterns. The parentage of an individual horse, either American Paint or American Quarter Horse, did not alter the likelihood of its entering the APHA Regular Registry. An empirical definition of the action of these genetic loci on the APHA‐defined white‐spotting phenotype will allow more accurate application of genome‐assisted selection for improving color production and the marketability of APHA horses.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of white‐spotting alleles, including W20, on phenotype in the American Paint Horse

et al. 2020

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“…WGS has recently identified a genetic cause of occipitoatlantoaxial malformation (OAAM) in an Arabian horse (Bordbari et al 2017) and dwarfism in a Miniature Shetland pony (Metzger et al 2017). WGS data have also been used to identify novel pigmentation variants (Henkel et al 2019). Finally, WGS has been used to investigate characteristics of highly selected breeds (Metzger et al.…”

Section: Genomics Tools and Resourcesmentioning

confidence: 99%

Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post‐genome era

et al. 2019

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Summary The horse reference genome from the Thoroughbred mare Twilight has been available for a decade and, together with advances in genomics technologies, has led to unparalleled developments in equine genomics. At the core of this progress is the continuing improvement of the quality, contiguity and completeness of the reference genome, and its functional annotation. Recent achievements include the release of the next version of the reference genome (EquCab3.0) and generation of a reference sequence for the Y chromosome. Horse satellite-free centromeres provide unique models for mammalian centromere research. Despite extremely low genetic diversity of the Y chromosome, it has been possible to trace patrilines of breeds and pedigrees and show that Y variation was lost in the past ~2300 years due to selective breeding. The high-quality reference genome has led to the development of three different SNP arrays and whole genome sequences (WGS) of almost 2000 modern individual horses. The collection of WGS of hundreds of ancient horses is unique and not available for any other domestic species. These tools and resources have led to global population studies dissecting the natural history of the species and genetic makeup and ancestry of modern breeds. Most importantly, the available tools and resources, together with the discovery of functional elements, are dissecting molecular causes of a growing number of Mendelian and complex traits. The improved understanding of molecular underpinnings of various traits, continues to benefit the health and performance of the horse while also serving as a model for complex disease across species.

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“…Visual inspection of the registration photographs for these 98 horses revealed that 31 possessed patterns consistent with white spotting loci. These 31 included many phenotypes resembling those generated by alleles known but not genotyped in this cohort, including SW4 , SW5 (Henkel et al, 2019), and more than 27 other alleles at the KIT locus. We also observed among these 31 horses some well-recognized patterns with yet unknown genetic etiology (i.e.…”

Section: Photographic Estimation Of Spotting Patterns Miscategorizes mentioning

confidence: 99%

Impact of white spotting alleles, includingW20, on phenotype in the American Paint Horse

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Palermo

Kahn

et al. 2019

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The American Paint Horse Association (APHA) officially records pedigree and performance information for their breed; these registered stock-type horses are valued for utility in work on the farm and ranch and as pleasure horses. As the name of the breed implies, the breed is also valued for attractive white spotting patterns on the coat. Current APHA procedures utilize visual inspections of photographs to determine if white spotting phenotypes exceed threshold anatomical landmarks considered by the association as characteristic of desirable patterns. Horses with sufficient white patterning enter the "Regular" registry, rather than the "Solid Paint-Bred" division. Genetic studies have now defined causative sequence variants for 35 alleles likely contributing to white spotting phenotypes in the horse. Here, the allele frequency was calculated for nine white spotting alleles commonly found in the American Paint horse breed using a sample of 1,065 APHA registered animals. Epistatic interactions were documented among five spotting loci, and with the MC1R and ASIP genes controlling black and red pigment production. The W20 allele within the KIT gene, in the absence of other spotting loci, was strongly associated with the APHA-defined white spotting phenotype (p = 1.86 x10 -18 ), refuting advertisements reporting that W20 acts only as a modifier of other white spotting patterns. An empirical definition of the action of these loci on the desired APHAdefined white spotting phenotype will allow for a more accurate application of genome-assisted selection in this breed, providing breeders with a powerful tool to increase the marketability of their horses.

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Whole‐genome sequencing reveals a large deletion in the MITF gene in horses with white spotted coat colour and increased risk of deafness

Cited by 27 publications

References 19 publications

Impact of white‐spotting alleles, including W20, on phenotype in the American Paint Horse

Impact of white‐spotting alleles, including W20, on phenotype in the American Paint Horse

Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post‐genome era

Impact of white spotting alleles, includingW20, on phenotype in the American Paint Horse

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