De-novovariants inXIRP1associated with polydactyly and polysyndactyly in Holstein cattle

Congenital polydactylous cattle are sporadically observed. Impairment of the limb patterning process due to altered control of the zone of polarizing activity (ZPA) was associated in several species with preaxial polydactyly and syndactyly. In cattle, the role of ZPA and other genes involved in limb patterning for polydactyly was not yet elucidated. Herein, we report on a preaxial type II polydactyly and a praeaxial type II+V polysyndactyly in two Holstein calves and screen whole genome sequencing data for associated variants. Using whole genome sequencing data of both affected calves did not show mutations in the candidate regions of ZRS and pZRS or in candidate genes associated with polydactyly, syndactyly and polysyndactyly in other species. Two indels, which are located inXIRP1within a common haplotype, were highly associated with the two phenotypes. Bioinformatic analyses retrieved an interaction betweenXIRP1andFGFR1, CTNNB1andCTNND1supporting a link between theXIRP1variants and embryonic limb patterning. The heterozygous haplotype was highly associated with the present polydactylous phenotypes due to dominant mode of inheritance with an incomplete penetrance in Holstein cattle.