The Rose-comb mutation in chickens constitutes a structural rearrangement causing both altered comb morphology and defective sperm motility

Comb morphology is a trait that shows considerable variability among domestic chickens. The Rose-comb mutation causes a drastically altered shape of the comb, whereas the Pea-comb mutation leads to a considerable reduction in the size of the comb. The combined effect of Rose-comb and Pea-comb is a comb shaped like a walnut, and the phenotype is consequently named walnut-comb. Both Pea-comb and Rose-comb are caused by structural changes in the genome leading to altered expression of important transcription factors. In a previous study we showed that Pea-comb is caused by misexpression of SOX5 during the development of the comb. In this study we report that Rose-comb is caused by a large inversion on chicken chromosome 7. The inversion moves the MNR2 gene to a new genomic location. This leads to misexpression of MNR2 during comb development, similar to the defect causing Pea-comb. Roosters that are homozygous for the Rose-comb inversion show poor sperm motility, and our results suggest that this is caused by the disruption of the CCDC108 gene that is located at one of the inversion breakpoints. CCDC108 is well conserved between chickens and humans, and this study establishes CCDC108 as a candidate gene for sperm motility disorders in humans.