A missense variant in the coil1A domain of the keratin 25 gene is associated with the dominant curly hair coat trait (Crd) in horse

Abstract

BackgroundCurly horses present a variety of curl phenotypes that are associated with various degrees of curliness of coat, mane, tail and ear hairs. Their origin is still a matter of debate and several genetic hypotheses have been formulated to explain the diversity in phenotype, including the combination of autosomal dominant and recessive alleles. Our purpose was to map the autosomal dominant curly hair locus and identify the causal variant using genome-wide association study (GWAS) and whole-genome sequencing approaches.ResultsA GWAS was performed using a Bayesian sparse linear mixed model, based on 51 curly and 19 straight-haired French and North American horses from 13 paternal families genotyped on the Illumina EquineSNP50 BeadChip. A single strong signal was observed on equine chromosome 11, in a region that encompasses the type I keratin gene cluster. This region was refined by haplotype analysis to a segment including 36 genes, among which are 10 keratin genes (KRT-10, -12, -20, -23, -24, -25, -26, -27, -28, -222). To comprehensively identify candidate causal variants within all these genes, whole-genome sequences were obtained for one heterozygous curly stallion and its straight-haired son. Among the four non-synonymous candidate variants identified and validated in the curly region, only variant g.21891160G>A in the KRT25 gene (KRT25:p.R89H) was in perfect agreement with haplotype status in the whole pedigree. Genetic association was then confirmed by genotyping a larger population consisting of 353 horses. However, five discordant curly horses were observed, which carried neither the variant nor the main haplotype associated with curliness. Sequencing of KRT25 for two discordant horses did not identify any other deleterious variant, which suggests locus rather than allelic heterogeneity for the curly phenotype.ConclusionsWe identified the KRT25:p.R89H variant as responsible for the dominant curly trait, but a second dominant locus may also be involved in the shape of hairs within North American Curly horses.Electronic supplementary materialThe online version of this article (10.1186/s12711-017-0359-5) contains supplementary material, which is available to authorized users.

An epistatic effect of KRT25 on SP6 is involved in curly coat in horses

“…Previous reports on curly horse pedigrees already suggested more than one genetic mechanism as the cause for curly hair 9 . An evaluation independent from this study identified the KRT25 variant in French and North American horses associated with curly hair 33 . In this work, which has been published during the review process of this manuscript, KRT25 -associated phenotypes were assessed by their outer appearance and assumed to be curly coated only.…”

“…Furthermore, it was postulated that there might be a second dominant locus for curly hair in particular in curly horses crossed with Missouri Foxtrotters potentially located in an incorrectly annotated region of the horse reference genome 33 . However, our analysis revealed that SP6 was located in an annotated region but was more difficult to detect due to the breeders unintentional mixing of horses harboring KRT25 variant with horses harboring SP6 variant.…”

Meta-analysis of genome-wide association studies identifies 8 novel loci involved in shape variation of human head hair

“…Mutations in various KRT genes have been linked to monogenic forms of hair abnormalities. For example, a missense variant in the coil1A domain of the keratin 25 gene has been recently reported to cause dominant curly hair in horse ( 33 ). Mutations in the KRT14 gene have been recently found to cause autosomal dominant Naegeli-Franceschetti-Jadassohn syndrome, in which hair changes represent a key symptom ( 34 ).…”

Integrated Analysis of Methylome and Transcriptome Changes Reveals the Underlying Regulatory Signatures Driving Curly Wool Transformation in Chinese Zhongwei Goats

“…A few studies have found that genetic polymorphisms in candidate genes can account for various hair traits in different species (Adhikari et al, 2016;Demars et al, 2017;Morgenthaler et al, 2017). Some critical signaling pathways, including the wingless-related integration site (WNT), ectodysplasin A receptor (EDAR), and bone morphogenetic proteins (BMP) pathways, are regarded as regulatory hubs during fiber development (Lu et al, 2016;Telerman et al, 2017).…”