In other species: rabbit , alpaca

Categories: Integument (skin) phene

Possibly relevant human trait(s) and/or gene(s) (MIM number): 615332 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2017

Mapping: By conducting a GWAS on half-sib families of the Romane breed, involving "two thousands lambs produced from ten unrelated rams", Demars et al. (2017) identified two QTL for fleece variation (woolly vs hairy) on chromosomes OAR13 and 25. Fine-mapping of the latter (larger-effect) QTL narrowed its location to "72 kb (7,435,557–7,508,217 bp)".

Lv et al. (2022) investigated whole genome sequencing data of 810 animals from 7 wild species and 158 domestic sheep populations. As part of the extended analysis, the authors "explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3′-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter"

Molecular basis: Following whole-genome sequencing of "seven selected individuals carrying either the “Q” ancestral hairy allele (Romanov, n = 2), the “q” modern woolly allele (Berrichon du Cher, n = 3) or both (heterozygous QTL sires, n = 2)", Demars et al. (2017) narrowed 18 variants within the candidate region down to one likely causal variant: "the "woolly" allele results from the insertion of an antisense EIF2S2 retrogene (called asEIF2S2) into the 3' UTR of the IRF2BP2 gene leading to an abnormal IRF2BP2 transcript". Demars et al. (2017) reported that this IRF2BP2^asEIF2S2 allele variant "segregated perfectly with the QTLOar25 status for the 8 QTL rams since heterozygous sires were heterozygous for the insertion and homozygous rams were homozygous for the mutated IRF2BP2^asEIF2S2 allele". These same authors also provided "evidence that this chimeric IRF2BP2/asEIF2S2 messenger 1) targets the genuine sense EIF2S2 RNA and 2) creates a long endogenous double-stranded RNA which alters the expression of both EIF2S2 and IRF2BP2 mRNA. This represents a unique example of a phenotype arising via a RNA-RNA hybrid, itself generated through a retroposition mechanism".

Wang et al. (2023; J Anim Sci Biotechnol) "found newborn lambs with coarse medullated wool, which were so called ancestral-like coarse (ALC) wool sheep, in a modern fine (MF) wool sheep population by MOET breeding. Using this model, [the authors] found the strongest differential methylation locus located in the second exon of the SOSTDC1 gene, which corresponds to the differential expression of the SOSTDC1 gene revealed by transcriptome analysis. Validation experiments showed that SOSTDC1 gene was specifically overexpressed in the nucleus of wool follicle stem cells of ALC wool lambs, indicating its importance in primary wool follicle development." The same group (Wang et al. 2023; Cell Biosci) reported later in the same year that the "ALC wool type of Merino sheep, which does not reduce wool quality but increases yield and adaptability, is regulated by epigenetic mechanisms in the imprinted Gtl2-miRNAs region on sheep chromosome 18, with the maternally expressed imprinted gene responsible for the ALC phenotype." Zhang et al. (2023) suggest that miRNAs within the imprinted Dlk1-Gtl2 region on chromosome 18 may "regulate the PI3K-AKT signaling pathway, thereby indicating the relevance of the Dlk1-Gtl2/PI3K-AKT axis in the context of fur traits."

Breed: INRA 401, France (Sheep) (VBO_0014736).
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 gene: