Phenotypes

Based on strong evidence obtained in Swiss Holsteins, Häfliger et al (2022) proposed KIR2DS1:p.Gln159* as the likely causal variant for haplotype HH13.

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 b...

By cloning and sequencing a very likely comparative candidate gene (based on the same disorder in humans), Shuster et al. (1992; PNAS) showed that this disorder in Holstein cattle is due to a missense mutation (c.383A>G) in the CD18 gene, now known as ITGB2. This mutation was confirmed in Daetwyler et al. (2014)'s analysis of whole-genome sequence data from 234 cattle, including key ancestors of the Holstein-Friesian, Fleckvieh and Jersey b...

Exome sequencing in the candidate region (see Mapping section) of 2 affected, one carrier and one homozygous normal animal enabled Hirano et al. (2013) to identify the causal mutation as a missense mutation (c.235G>C; p.Val79Leu) in the IARS gene which encodes isoleucyl-tRNA synthetase. Hirano et al. (2016) reported that "the [above] homozygous IARS mutation not only causes calf death, but also embryonic or fetal death.

This single-locus autosomal dominant trait confers increased thermotolerance within the breeds in which it originated (Senepol and Carora; Olsen et al., 2003) and also within Hosteins, into which it was introgressed (Dikmen et al., 2008; 2014). In the USA, FDA determined in March 2022 that beef cattle with a genome edit to the PRLR gene and their offspring do not raise any safety concerns. "Based on the safety of consumption of meat from conve...