In other species: helmeted guineafowl , turkey

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: Z-linked

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2008

Species-specific symbol: K(s)

Species-specific description: The difference between K- (slow-feathering) and kk (fast-feathering) chickens is discernible immediately after hatching. This difference has been exploited as a far simpler means of sexing day-old chickens than the traditional method of vent sexing.

History: The (Z-linked) inheritance of this trait was reported by Serebrosky (1922) as already well known, but without any relevant citation.

Inheritance: The locus is Z-linked, with slow-feathering being dominant to fast or rapid feathering (the wild type)

Markers: Smith and Crittenden (1988) reported that the K allele "is associated with an endogenous provirus gene, ev21". Smith and Fadly (1994) concluded that "ev21 and K appear to be less than .3 cM apart".

Molecular basis: Elferink et al. (2008) reported a likely causal variant as "a duplication at the K allele and sequence analysis of the breakpoint junction indicated a tandem duplication of 176,324 basepairs. The tandem duplication of this region results in the partial duplication of two genes; the prolactin receptor [PRLR] and the gene encoding sperm flagellar protein 2 [SPEF2]. Sequence analysis revealed that the duplication is similar in Broiler and White Leghorn. In addition, twelve late feathering animals, including Broiler, White Leghorn, and Brown Layer lines, contained a 78 bp breakpoint junction fragment, indicating that the duplication is similar in all breeds." Luo et al. (2012) reported evidence "that increasing PRLR expression that resulted from the special variant on chicken Z chromosome caused the late-feathering phenotype" Bu et al. (2013) reported evidence that the partially duplicated PRLR "is predicted to encode a membrane-spanning receptor of 683 amino acids, which is nearly identical to the original PRLR, except for its lack of a 149-amino acid C-terminal tail." Liu et al. (2020): Research by two master’s students (J. Li (2012) and Z. Huang (2014) cited by Liu et al. 2020) “found that many EF [early-feathering] feathering chicks had the tandem duplication in Chinese native chicken breeds, which suggested that dPRLR [duplicated prolactin receptor] was not the determinant of the LF [late-feathering] feathering phenotype. Luo et al. (2012) found that the expression level of the prolactin receptor (PRLR) gene in LF chickens was 1.78 times higher than that in EF chickens. However, Zhao et al. (2016) reported that there was no significant difference between the PRLR expression levels of the EF and LF chicks in their study. Because there was an extremely significant difference in the expression level of SPEF2, but not of PRLR between the EF and LF chickens, Zhao et al. (2016) suggested that SPEF2 should be a good candidate gene for the chicken feather rate phenotype rather than PRLR.” Liu et al. (2020) conducted a genome-wide association study (GWAS) in Shouguang chicks “to map candidate genomic regions related to the feather rate” and analysed “RNA sequencing data from the hair follicle tissue of the EF and LF samples. …. The sperm flagellar 2 gene (SPEF2) and prolactin receptor (PRLR) gene were the only two overlapping genes between the results of GWAS and differential expression analysis, which implies that SPEF2 and PRLR are possible candidate genes for the formation of the chicken feathering phenotype in the present study.”

Clinical features: The K(s) mutation is a mixed blessing. While it is obviously advantageous in terms of the slow-feathering phenotype it has created, it is disadvantageous because it produces infectious viral particles (called endogenous viruses). These viruses are transmitted congenitally from hens with K(s) to all of their offspring. This does not seem to harm those offspring that also inherit K(s), i.e. the slow-feathering offspring. But in the offspring that have not inherited K(s) (i.e. the fast-feathering offspring), the presence of endogenous viral particles induces immunological tolerance to the virus, which renders the chickens unable to mount an effective immune response aganist exogenous viral particles, resulting in poorer performance and increased mortality due to tumours induced by the exogenous virus. Fortunately, there are various ways to overcome at least some of this disadvantage, such as vaccination of the slow-feathering dams, who then provide protection to their offspring via the transfer of maternal antibodies.

Genetic testing: Elferink et al. (2008): "The breakpoint junction was used to develop a TaqMan-based quantitative PCR test to allow distinction between homozygous and heterozygous late feathering males. In total, 85.3% of the animals tested were correctly assigned, 14.7% were unassigned and no animals were incorrectly assigned." Takenouchi et al. (2018) provided evidence that "regarding LF [late feathering] expression, the results indicated that ID [incomplete duplication of the prolactin receptor (PRLR) and sperm flagellar protein 2 (SPEF2) genes] is responsible, but ev21 [endogenous ev21 gene] is not required, which led them to recommend that "Henceforth, ID should be used as a molecular marker to detect LF [later feathering] birds instead of ev21." Based on the findings reported by Liu et al. (2020) further research will be required to identify any variation within the duplication that is causal for the feathering phenotype to develop reliable genetic testing for all breeds. Shen et al. (2023): developed a multiplex PCR test to identify early feathering (EF) and late feathering (LF) homozygote, and heterozygote chicken. The authors tested "413 chickens of six native Chinese breeds with this method. The identification was consistent with the sex and phenotype records of the chickens. ... In order to further verify the accuracy of this test in distinguishing homozygote and heterozygote males, 152 LF males were mated with EF females, and the results of the offspring's phenotypes were consistent with our expectations. Our results support tandem duplication as molecular markers of LF, and this new test is applicable to all LF chickens associated with tandem duplication."

Associated gene: