Comparison of sequence of the 713kb candidate region (mentioned in the mapping section above) in an obligate carrier, one of its offspring, 43 members of the Fleckvieh breed (in which the disorder has never been reported) and 191 non-Fleckviehs from the 1000-bulls project revealed 2 candidate causal SNVs: a coding variant and an intronic variant of the gene UBE3B, which encodes ubiquitin protein ligase E3B, and mutations in which cause a similar syndrome in humans (see MIM links above). Sequencing of animals in other families in which the disorder segregates pointed to the coding variant (rs475678587G>A; p.E692E; Chr17:65,921,497 bp) as being causal. This synonymous variant occurs at the very last nucleotide of exon 23, at the junction with intron 23, resulting in skipping of the entire exon 23. As reported by Venhoranta et al. (2014), this results "in an altered protein lacking 40 amino acids, of which 20 are located in the conserved HECT-domain, the catalytic site of the UBE3B protein." In their table of reduced-fertility haplotypes, Cole et al. (2014) list this UBE3B mutation as being causal for the infertility effect of haplotyoe AH1.
