Categories: Integument (skin) phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 176761 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2014

Species-specific description: This single-locus autosomal dominant trait confers increased thermotolerance within the breeds in which it originated (Senepol and Carora; Olsen et al., 2003) and also within Hosteins, into which it was introgressed (Dikmen et al., 2008; 2014). In the USA, FDA has determined in March 2022 that beef cattle with a genome edit to the PRLR gene and their offspring do not raise any safety concerns. "Based on the safety of consumption of meat from conventional breeds with the same mutation, the FDA finds no reason to regulate these CRISPR cattle. ... These cattle are the third genetically altered animals to be approved by the FDA, after AquaBounty’s AquAdvantage salmon and Revivicor’s GalSafe pigs." (PMID:35418643) (GMO)

Inheritance: Olson et al. (2003) reported "a major gene (designated as the slick hair gene), dominant in mode of inheritance, that is responsible for producing a very short, sleek hair coat . . . in Senepol cattle and criollo (Spanish origin) breeds in Central and South America . . .[and] in a Venezuelan composite breed, the Carora, formed from the Brown Swiss and a Venezuelan criollo breed". Sosa et al. (2021) "evaluated whether the inheritance of the SLICK1 allele ...is inherited in a fashion consistent with Hardy–Weinberg equilibrium. It was hypothesized that any deleterious effect of inheriting the allele on embryonic or fetal function would result in reduced frequency of the allele in offspring. A total of 525 Holstein and Senepol cattle produced from matings involving one or both parents with the SLICK1 allele were genotyped. The observed frequency of the SLICK1 allele (0.247) was not significantly different than the expected frequency of 0.269. These results support the idea that inheritance of the SLICK1 allele does not act in the embryo or fetus to modify its competence to complete development to term."

Mapping: From a genome scan with microsatellite markers, Mariasegaram et al. (2007) mapped this locus to a region of chromosome BTA20. Using a 50k SNP chip, Flori et al. (2012) refined this region to just one positional candidate gene, namely "Retinoic Acid induced 14 gene (RAI14 or NORPEG)". Huson et al. (2014) narrowed this region even further, to "a 0.8 Mb (37.7-38.5 Mb) consensus region for the SLICK locus on BTA20 in which contains SKP2 and SPEF2 as possible candidate genes". From various lines of evidence, the authors concluded that there are "potentially two mutations, one common to Senepol and Romosinuano and another in Carora, effecting genes contained within our refined location for the SLICK locus."

Molecular basis: By sequencing the most likely positional functional candidate gene within the BTA20 region to which this trait had been mapped (see Mapping section), Littlejohn et al. (2014) identified a causal mutation as "a single homozygous frameshift mutation . . . consisting of a single base deletion in exon 10 that introduces a frameshift and a premature stop codon (p.(Ala461fs) and loss of 120 C-terminal amino acids from the long isoform of the receptor (ss1067289408; chr20:39136558GC>G". Porto-Neto et al. (2018) identified two other likely causal variants in the same PRLR gene, namely the stop-gained (nonsense) variants p.Ser465∗ (in the Limonero breed) and p.Arg497∗ (in the Carora and Limonero breeds). These two variants "explained almost 90% of investigated cases of animals that had slick coats, but which also did not carry the Senepol slick allele"; which indicates that there are more likely causal variants for slick hair yet to be discovered. Flórez Murillo et al. (2021) discovered three new variants, namely SLICK4, SLICK5 and SLICK6 (details in variant table below).
Zayas et al. (2024) "evaluated the effectiveness of genetic introgression of the SLICK1 allele derived from Senepol cattle into the Holstein breed to enhance thermotolerance. ... The study demonstrates the successful use of genetic interventions to improve livestock resilience against environmental challenges without significantly disrupting the recipient breed's genetic structure."

Genetic engineering: Yes - in addition to the occurrence of natural variants, variants have been created artificially, e.g. by genetic engineering or gene editing
Have human generated variants been created, e.g. through genetic engineering and gene editing

Breeds: Blanco Orejinegro, Colombia (Cattle) (VBO_0004602), Carora, Venezuela (Bolivarian Republic of) (Cattle) (VBO_0005370), Casanareño, Colombia (Cattle) (VBO_0004603), Chino Santandereano, Colombia (Cattle) (VBO_0004605), Costeno con Cuernos (Cattle) (VBO_0016934), Criollo Caqueteño, Colombia (Cattle) (VBO_0004607), Criollo Lechero Tropical, Mexico (Cattle) (VBO_0004281), Hartón del Valle, Colombia (Cattle) (VBO_0004609), Holstein (black and white) (Cattle) (VBO_0000237), Limonero, Venezuela (Bolivarian Republic of) (Cattle) (VBO_0005372), Romosinuano, Venezuela (Bolivarian Republic of) (Cattle) (VBO_0005376), Senepol (Cattle) (VBO_0000371), Tropicarne, Mexico (Cattle) (VBO_0005086).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: