Phenotypes

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.

The report of the use of a DNA genotyping test by Healy et al. (1995), citing a personal communication from G.S. Johnson at the University of Missouri, implied that the molecular basis of this disorder within the gene for ferrochelatase had been determined by Dr Johnson. Jenkins et al. (1998) appear to have been the first to publicly report the molecular basis of this disorder. They did so by cloning and sequencing a very likely comparative ca...

Recognising the close resemblance of this disorder in Chianina cattle to Brody disease in humans, Drögemüller et al. (2008) illustrated the power of the candidate-gene approach by showing that this disorder in Chianina cattle is due to a missense mutation in the bovine version of the "Brody gene" - ATP2A1. Interestingly, another mutation in this same gene causes a far more severe set of clinical signs: congenital muscular dystonia 1 (OMIA 0014...

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 simil...

Häfliger et al. (2020; PMID 32069517): "Whole‐genome sequencing of one case, variant filtering against controls and genotyping of a larger cohort of Cika cattle led to the detection of a likely pathogenic protein‐changing variant perfectly associated with the disease: a missense variant on chromosome 6 in ADAMTS3 (NM_001192797.1: c.1222C>T), which affects an evolutionary conserved residue (NP_001179726.1: p.(His408Tyr))"

Boulling et al. (2024) "Using homozygosity mapping, whole genome sequencing of two affected individuals, and filtering for variants found in 1,867 control genomes, [the authors] reduced the list of candidate variants to a single deep intronic substitution in GNPAT (g.4,039,268G>A on Chromosome 28 of the ARS-UCD1.2 bovine genome assembly [omia.variant:1804])." The variant segregated with the disease in 21 affected animals and 26 available pa...

By sequencing a strong positional candidate gene, namely TWIST1, Capitan et al. (2011) identified a small duplication (c.148_157dup (p.A56RfsX87)) that inactivates the gene. This frameshift mutation segregates perfectly with type 2 scurs.

Jacinto et al. (2021) characterized "the pathological phenotype of a Romagnola stillborn calf with skeletal-cardio-enteric dysplasia and ... [identified] a genetic cause by whole-genome sequencing (WGS)."

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...

Hiltpold et al. (2022) investigated a Brown Swiss bull with low semen quality: "The genome of this bull was sequenced at a 12× coverage to investigate a possible genetic cause. Comparing the sequence variant genotypes of this bull with those from 397 fertile bulls revealed a 1-bp deletion in the coding sequence of the QRICH2 gene which encodes the glutamine rich 2 protein, as a compelling candidate causal variant. This 1-bp deletion causes a f...

By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Inaba et al. (1996) showed in a population of Japanese Black cattle, that this disorder is due to a nonsense mutation (CGA>TGA; Arg>Stop) in the gene for band 3 of red cell membrane, at the position corresponding to codon 646 of the human gene. The lack of this protein produces very unstable red-cell membranes, resulting in anaemi...

Syndactyly has been reported in many breeds of cattle in many countries. Most of the documentation, however, concerns its occurrence in US Holsteins, where, as a result of the siring of more than 60,000 calves by a bull who was subsequently shown to be a carrier, the disorder attracted considerable attention (Anon., 1967). The possibility that artificial selection favouring heterozygotes may have contributed to the unacceptably high frequency ...

"Affected animals have a crooked tail and shortened head, growth retardation, extreme muscularity and spastic paresia, although some characteristics show variable penetrance. CTS is not lethal per se, but causes substantial economic losses due to growth retardation and treatment." (Charlier et al., 2008)

On the strength of a clear candidate gene in which mutations cause the same disorder in dogs (OMIA 001003-9615), Boudreaux et al. (2007) reported that this disorder in a Simmental calf is due to a missense mutation (c.701T>C) in the CalDAG-GEFI gene which is now called RASGRP2. Jansen et al. (2013) reported that "Sanger sequencing confirmed that all thrombopathic animals are homozygous for the [same] pertinent amino acid exchange (c.701T &g...

In a neat piece of comparative detective work, Lunden et al. (2002; Genome Research 12:1885-1888) investigated whether the fishy off-flavour occasionally reported in cow's milk could be an animal model of fish-odor syndrome in humans, an inborn error of metabolism characterised by a fishy body odor, and known to be due to mutations in the gene for flavin-containing mono-oxygenase 3 (FMO3). They were able to show that this is, indeed, the case:...