For eight of the nine haplotypes with a significant effect on calving rate (see Mapping section), Fritz et al. (2013) searched for causal mutations via whole-genome sequence data from 25 Holstein, 11 Montbéliarde and nine Normande bulls which had made major contributions to their breed. Specifically, they filtered "for mutations that were (a) located at+or –6 Mb from the detected haplotype (b) carried in the heterozygous state by the carrier bulls and (c) absent from the non carrier bulls from the three breeds" and then examined identified polymorphisms for their likely effect on protein structure and function. For HH4, Fritz et al. (2013) provided convincing evidence for a candidate causal mutation, namely a missense mutation (g.1277227A.C; UMD 3.1 genome assembly) in the GART gene (which encodes glycinamide ribonucleotide transformylase), leading to p.N290T.
