Categories: Homeostasis / metabolism phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 107910 (gene) , 139300 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1991

Species-specific symbol: Hf

Species-specific description: The typical feathering of hens is part of their secondary sexual characteristics, produced by the action of oestrogen. Much of this oestrogen is produced from androgen in the ovaries by the enzyme aromatase. In certain strains of two breeds of chicken, namely the Sebright Bantam and the Golden Campine, roosters have the same feathering as hens, rather than the typical male form of feathering. This disorder is called henny feathering. It results from a mutation in the aromatase gene, causing the gene to be expressed in the skin of both sexes. In males, this leads to abnormally high levels of oestrogen, which in turn produces henny feathering. Henny feathering is interesting because it illustrates that not all mutations result in loss of activity; some mutations can cause a gene to be switched on in cells in which it is normally inactive.

History: It seems that the henny feathering trait was first observed by Sir John Sebright in 1800 (Tegetmeier, 1867), and became a distinguishing feature of the Sebright Bantam breed. From this breed, the mutation appears to have spread to other breeds, including the Golden Campine.

Inheritance: The aromatase gene is autosomal, but the form of inheritance of henny feathering is not what is normally seen with an autosomal mutation, because the phenotype associated with the mutation (henny feathering in males) can be seen only in males. This is an example of a sex-limited trait. Furthermore, the normal expression of the gene is seen only in females. Thus the two alleles at the one locus give rise to the two possible forms of sex-limited inheritance. The henny-feathering mutation also illustrates how two alleles can present more than one form of inheritance, depending on which trait is being considered. With respect to aromatase activity, gene action is co-dominant, i.e. heterozygotes have an enzyme activity mid-way between that of the two homozygotes. In this case, however, the activity in the skin of the normal homozygote is zero. With respect to feathering, the mutant is dominant, because heterozygotes produce sufficient enzyme in the skin, and hence sufficient oestrogen, to cause henny feathering.

Mapping: Li et al. (2019) showed that the exact location of the insertion is "at position 9,683,879 bp on chromosome 10 of GalGal6, which is in the 5′ untranslated region (5’UTR) of CYP19A1".

Molecular basis: By cloning and sequencing a very likely candidate gene (based on knowledge that the disorder is due to aberrant expression of the enzyme aromatase) Matsumine et al. (1991) showed that the disorder is due to the terminal repeat sequence of a retrovirus that has been inserted into the 5' promoter region of the aromatase gene. This terminal repeat has a promoter of its own, which causes the aromatase gene to be switched on in atypical places, such as the skin of both sexes, giving rise to the henny-feathering trait in males. The actual peptide produced by the mutant allele is exactly the same as that produced by the normal allele, as we would expect for such a mutation. This disorder is the first insertion mutation documented in any domesticated species of animal. Twenty-eight years after the above pioneering discovery, Li et al. (2019) utilised the full power of advances in genomic technology to fill in the gaps in knowledge understandably inherent in the original discovery of the Hf likely causal variant. They showed that the insertion is 7524bp and "contains an intact endogenous retrovirus [ERV] that was not found in chickens representing 31 different breeds not showing henny feathering or in samples of the ancestral red junglefowl. The sequence shows over 99% sequence identity to the avian leukosis virus ev-1 and ev-21 strains, suggesting a recent integration. The ERV 3’LTR, containing a powerful transcriptional enhancer and core promoter with TATA box together with binding sites for EFIII and Ig/EBP inside the CYP19A1 5′ untranslated region, was detected partially in an aromatase transcript, which present a plausible explanation for ectopic expression of aromatase in non-ovarian tissues underlying the henny feathering phenotype".

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

Clinical features: Apart from the hen-like feathers, males with this trait have a substantially reduced reproductive ability, probably because the increased levels of plasma oestrogen inhibit spermatogenesis (George et al., 1990).

Associated gene: