Phenotypes

Bolcato et al. (2025): Genetic analysis identified a missense variant in WDR33 (omia.variant:1814) that was heterozygous in both analyzed cases [Belgian Blue cross calves] and in an estimated 40% of the paternal gametes of the mosaic [Belgian Blue] founder, but absent in both dams and controls. ... The genetic findings were most consistent with a likely pathogenic dominant de novo mutation in WDR33 as the underlying cause of the observed conge...

Braun et al. (2021): "Filtering whole genome sequencing data revealed a private frameshift variant within the candidate gene ZIC2 in the affected calf. . . . A 1-bp deletion (g.80722845TC>T; ARS-UCD1.2:g.76742066TC>T) in exon 4 of the candidate gene ZIC2 . . . was heterozygous in the affected calf and homozygous wild type in both parents and all other Limousin herdmates and private controls. . . . The origin of this variant is most likel...

Using inferred haplotypes from the 1000-bull-genomes project, Hayes et al. (2013) announced the discovery of the likely HH3 causal mutation. Using exome capture and next-gen sequencing, McClure et al. (2014) confirmed and validated Hayes et al. (2013)'s causal mutation mutation as "a non-synonymous SNP (T/C) within exon 24 of the Structural Maintenance of Chromosomes 2 (SMC2) on Chromosome 8 at position 95,410,507 (UMD3.1). This polymorphism ...

Sonstegard et al (2013) investigated the lethal Jersey haplotype, namely haplotype JH1 on chromosome BTA15 (see Mapping section). They first refined the haplotype "to a 15-marker window (15,162,470 to 15,949,175)" and then obtained whole-genome sequence from 11 bulls carrying this haplotype. Analysis of the sequence of these carriers in the candidate region revealed a "high-impact stop-gain SNP located at position 15,707,169 on BTA15. This C-t...

As reported by Kadri et al. (2014), one of the genes in the deletion (see Mapping section), namely RNASEH2B, is "known to cause embryonic lethality when knocked-out in the mouse". Subsequent investigations confirmed that this deletion is a recessive embryonic lethal in cattle but "is associated with a positive effect on milk yield and composition", which results in selection favouring heterozygotes (balancing selection), thereby maintaining th...

Jacinto et al. (2022): "A trio whole-genome sequencing approach was carried out and identified a private homozygous missense variant in LAMB1 affecting a conserved residue (p.Arg668Cys)."

Illustrating the enormous power of genomic tools, Wiedemar et al. (2015) were able to identify a likely causal mutation for a previously unrecorded disease phenotype in just a single calf.

Nogueira et al. (2022) "A rare SNP, predicted to be deleterious was discovered within a conserved WD40 domain repeat-encoding region ... of the bovine autosomal ... EML5 gene ... in an Angus bull ... with low fertility." The authors "demonstrate that this mutant allele is present in many breeds world-wide." 

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...

Thomsen et al. (2010) showed that this disorder is due to a missense mutation (R560Q) at a site that is invariant from insects to mammals in the gene encoding spastin (SPAST or SPG4). In their table of reduced-fertility haplotypes, Cole et al. (2014) list this SPAST mutation as being the causal mutation for haplotype BHD.