Categories: Pigmentation phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 155555 (gene) , 266300 (trait) , 203200 (trait) , 155550 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2016

Species-specific name: rat-tail syndrome

Species-specific symbol: RTS

Species-specific description: Knaust et al. (2016) reported: "evidence that the RTS phenotype results from an epistatic interaction between three independent loci: dilution (that corresponds to the PMEL gene at 55 Mb on BTA5), extension (that corresponds to the MC1R gene on BTA18) and the RTS locus that is located in the interval between 14 and 22 Mb on BTA5. The prerequisites for expression of the RTS phenotype are a eumelanic background due to the presence of the dominant ED allele at MC1R (extension locus) and a heterozygous genotype at the PMEL gene variant c.64G>A (dilution locus). The positions of the RTS and dilution loci on BTA5 are clearly distinct."

Mapping: Knaust et al. (2016) mapped RTS to a region of chromosome BTA5 "between 14 and 22 Mb ".

Molecular basis: Jolly et al. (2008) summarised the results in an unpublished thesis by Hecht (2006) as: "In a genetic study of an experimental Simmental crossbred herd, the coat-colour dilution/hypotrichosis phenotype segregated with a three-base (CTT) deletion at nucleotide 54 in exon 1 of the PMel17 gene (Hecht 2006). Although the study was not conclusive, this is the presumptive mutation for the disorder. A second single nucleotide polymorphism, a C→A transition in exon 11 in the second nucleotide of codon 612 of the same PMel17 gene, segregated with most, but not all, animals with the same phenotype." Reporting their investigation of the same disorder in Hereford-cross cattle, Jolly et al. (2008) identified the same two mutations: "a three-base deletion (CTT) at nucleotide 54" in exon 1 and "a single missence [sic] mutation in one copy of this exon, resulting in a C→A substitution in codon 612" in exon 11. However, as reported by Knaust et al. (2016), in two papers published in 2007 (both listed below), Kühn and Weikard "showed that neither mutations in the coding and regulatory regions of the PMEL gene, nor splicing variants of this gene are associated with RTS". Knaust et al. (2016) went on to report that RTS in a German Holstein x Charolais population is due to the interaction of three loci: "In this population, the RTS is exclusively expressed in animals with a eumelanic background that is due to the dominant ED allele at the melanocortin 1 receptor gene located on Bos taurus autosome (BTA) 18. In addition, only the individuals that are heterozygous at the dilution locus on BTA5 that corresponds to the premelanosome protein or silver gene variant c.64G>A were classified as displaying a RTS phenotype. Linkage and whole-genome association analyses using different models and different pedigrees allowed us to map a third locus (hereafter referred to as the RTS locus) that is essential for the expression of the RTS phenotype to the chromosomal region between 14 and 22 Mb on BTA5. Our findings clearly demonstrate that the RTS and dilution loci are distinct loci on BTA5". Knaust et al. (2020) "concluded that at least in cattle PMEL potentially has additional, yet unexplored functions, which might contribute to effects of PMEL mutations on pheomelanin coat color dilution and charcoal coat color in RTS animals". Hauser et al. (2020) reported 33 Swiss cattle with rat-tail f pigmentation-associated hypotrichosis were all heterozygous for dominant black (E^D) and recessive red (e) variants at the MC1R locus and were also heterozygous at the PMEL locus for a dilution variant. These authors noted that "The introgression of Holstein cattle into the Original Simmental. breed, which has been practised for decades, explains the occasional occurrence of this phenomenon in Swiss cattle breeding."

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Breed: Hereford (Cattle) (VBO_0000232).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated genes: