A de novo frameshift mutation in ZEB2 causes polledness, abnormal skull shape, small body stature and subfertility in Fleckvieh cattle.

Polledness in cattle is an autosomal dominant trait. Previous studies have revealed allelic heterogeneity at the polled locus and four different variants were identified, all in intergenic regions. In this study, we report a case of polled bull (FV-Polled1) born to horned parents, indicating a de novo origin of this polled condition. Using 50K genotyping and whole genome sequencing data, we identified on chromosome 2 an 11-bp deletion (AC_000159.1:g.52364063_52364073del; Del11) in the second exon of ZEB2 gene as the causal mutation for this de novo polled condition. We predicted that the deletion would shorten the protein product of ZEB2 by almost 91%. Moreover, we showed that all animals carrying Del11 mutation displayed symptoms similar to Mowat-Wilson syndrome (MWS) in humans, which is also associated with genetic variations in ZEB2. The symptoms in cattle include delayed maturity, small body stature and abnormal shape of skull. This is the first report of a de novo dominant mutation affecting only ZEB2 and associated with a genetic absence of horns. Therefore our results demonstrate undoubtedly that ZEB2 plays an important role in the process of horn ontogenesis as well as in the regulation of overall development and growth of animals.

Are scurs in heterozygous polled (Pp) cattle a complex quantitative trait?

BACKGROUND: Breeding genetically hornless, i.e. polled, cattle provides an animal welfare-friendly and non-invasive alternative to the dehorning of calves. However, the molecular regulation of the development of horns in cattle is still poorly understood. Studying genetic characters such as polledness and scurs, can provide valuable insights into this process. Scurs are hornlike formations that occur occasionally in a wide variety of sizes and forms as an unexpected phenotype when breeding polled cattle. METHODS: We present a unique dataset of 885 Holstein-Friesian cattle with polled parentage. The horn phenotype was carefully examined, and the phenotypic heterogeneity of the trait is described. Using a direct gene test for polledness, the polled genotype of the animals was determined. Subsequently, the existence of a putative scurs locus was investigated using high-density genotype data of a selected subset of 232 animals and two mapping approaches: mixed linear model-based association analyses and combined linkage disequilibrium and linkage analysis. RESULTS: The results of an exploratory data analysis indicated that the expression of scurs depends on age at phenotyping, sex and polled genotype. Scurs were more prevalent in males than in females. Moreover, homozygous polled animals did not express any pronounced scurs and we found that the Friesian polled allele suppresses the development of scurs more efficiently than the Celtic polled allele. Combined linkage and linkage disequilibrium mapping revealed four genome-wide significant loci that affect the development of scurs, one on BTA5 and three on BTA12. Moreover, suggestive associations were detected on BTA16, 18 and 23. The mixed linear model-based association analysis supports the results of the combined linkage and linkage disequilibrium analysis. None of the mapping approaches provided convincing evidence for a monogenic inheritance of scurs. CONCLUSIONS: Our results contradict the initial and still broadly accepted model for the inheritance of horns and scurs. We hypothesise an oligogenetic model to explain the development of scurs and polledness.