Categories: Craniofacial phene

Possibly relevant human trait(s) and/or gene(s) (MIM number): 614270 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2012

Species-specific symbol: R

History: This trait is one of the first six animal traits to be shown to be inherited in a Mendelian manner, in adjacent papers by Bateson and Saunders (1902; pages 87-124) and Bateson and Saunders (1902; pages 125-160). The other five traits are Pea-comb (OMIA 000782-9031), Polydactyly (OMIA 000810-9031), Dominant White (OMIA 000373-9031), and Yellow skin (OMIA 001449-9031) in chickens; and polled (OMIA 000483-9913) in cattle. This trait was also one of the first pair of loci in farm animals to be shown to be linked autosomally, when Serebrovsky and Petrov (1928) reported a recombination fraction of 8% between this locus and Creeper (OMIA 000006-9031). Linkage between these two loci was confirmed (with a smaller recombination fraction) by Landauer (1932, 1933) and Taylor (1934).

Mapping: The linkage group to which this locus belongs became known as linkage group II, which was later shown to be located on chromosome GGA7 (Vaez et al., 2008). A GGA7 location was confirmed by Dorshorst et al. (2010), the most likely region being 16.9–22.4 Mb.

Molecular basis: Having observed substantial suppression of recombination in the vicinity of the mapped Rose-comb locus on chromosome GGA7, Imsland et al. (2012) suspected that the trait could be associated with an inversion. Genomic resequencing subsequently confirmed "a 7.38 Mb inversion with breakpoints located approximately at 16.50 Mb and 23.88 Mb". The Rose-comb phenotype arises because the inversion results in "the relocalization of the MNR2 homeodomain protein gene leading to transient ectopic expression of MNR2 during comb development". Naming this Rose-comb allele R1, Imsland et al. (2012) also report a second Rose-comb allele (R2), which "must have originated by a recombination event between the wild-type allele at position 16.50 Mb and the R1 allele at position 23.79 Mb in the inverted region . . . . The consequence of this recombination event is that R2 does not carry the entire inversion but instead has two duplicated segments, one 91 kb fragment (23,790,414–23,881,384 bp) that represents a remaining fragment of the inverted region together with a small duplicated fragment of 198 bp (16,499,583–16,499,781 bp) that is present on both sides of the 91 kb duplication". The same authors also were able to provide a molecular explanation for the very first example of epistasis (interaction between genes) ever reported (by Bateson and Punnett, 1908), namely the walnut comb, which results from the combined action of Rose-comb and Pea-comb alleles (see OMIA 000782-9031): "Transient ectopic expression of MNR2 and SOX5 (causing the Pea-comb phenotype) occurs in the same population of mesenchymal cells and with at least partially overlapping expression in individual cells in the comb primordium". Finally, Imsland et al. (2012) were also able to provide an explanation for the well-documented pleiotropic effect of Rose-comb, namely that male homozygotes have poor sperm motility (see Crawford and Merritt, 1963, and many more recent references in the list below). The authors propose that this pleiotropy arises from the inversion breakpoint of allele R1 coinciding with a gene (CCDC108) whose encoded peptide includes a major sperm protein domain.

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

Associated gene: