Phenotypes

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))"

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...

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...

By examining three comparative positional candidate genes from their mapping results (see Mapping section), Krebs et al. (2007) reported strong evidence that this disorder in cattle is due to a mutation in "FVT1, encoding 3-ketodihydrosphingosine reductase, which catalyzes a crucial step in the glycosphingolipid metabolism". Specifically, the mutation is "a G-to-A missense mutation that changes Ala-175 to Thr". Interestingly, the FVT1 gene, of...

Stillbirth occurs in many different forms, many of which are not inherited, some are multifactorial and others are single locus disorders.

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 ...

Duchesne et al. (2017) identified SNPs in the mapped candidate region by comparison of whole-genome sequence of two homozygous affecteds, one heterozygote and one homozygote normal. Filtering of those SNPs by consistency with presumed genotype based on pedigree, with occurrence only within this breed, and by severity of presumed function enabled Duchesne et al. (2017) to identifiy a "C/T SLC25A46 substitution [c.376C>T that] leads to replac...

"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)

In a remarkable indication of the power of modern genomic tools, Hofstetter et al. (2017) reported a novel form of curly coat in a single Brown Swiss calf, the offspring of two normal-coated parents. By whole-genome sequencing of the calf and its sire and dam, followed by informed interrogation of the sequence data (as described below), these authors were able to identify a likely causal variant in a gene which, when mutated in humans, gives r...

Kromik et al. (2015; Genetics): c.196A>G; p.66Lys>Glu; NM_001192985.1

Cloning and sequencing of the bovine gene encoding molybdopterin cofactor sulfurase (MCSU, now called MOCOS) in normal and affected cattle, by Watanabe et al. (2000), revealed the causal mutation to be a 3bp deletion (c.769_771delTAC) of codon 257 (deleting Tyr) in the MOCOS gene (omia.variant:446). Murgiano et al. (2016) discovered a different mutation in the MUCOS gene as the likely cause in Tyrolean Grey cattle: "1 bp deletion in the molybd...