Phenotypes

Charlier et al. (2016): nonsense (stop-gain) p.Lys693∗

In a remarkable indication of the power of whole-genome sequence analysis, Daetwyler et al. (2014) identified a causal mutation for this disorder in Holstein Friesian cattle as a missense mutation (g.32475732G>A [UMD3.1 reference sequence]; p.Gly960Arg, omia.variant:223) in the COL2A1 gene (which encodes the alpha-1 chain of type II collagen), by comparing the sequence of only two affected calves with sequence from bulls in the 1000-bull-ge...

Jacinto et al. (2022) reported that "Whole genome sequencing (WGS) was performed using genomic DNA obtained from ear tissue from the [affected] calf. . . . Variant filtering did not reveal any private homozygous protein-changing variants present in the genome of the affected calf, making a possible recessive inheritance unlikely. Assuming that a spontaneous mutation affecting a protein-coding gene is the cause, filtering for private heterozygo...

Iso-Touru et al. (2019): "Whole genome-sequencing uncovered that both asthenospermic bulls were homozygous for a mutation that disrupts a canonical 5' splice donor site of CCDC189 encoding the coiled-coil domain containing protein 189. Transcription analysis showed that the derived allele activates a cryptic splice site resulting in a frameshift and premature termination of translation. The mutated CCDC189 protein is truncated by more than 40%...

Nonsense mutation: c.493C>T "at position 65,369,074 in [exon 4 of] the CEP250 gene" "that encodes the centrosomal protein C-Nap1". The mutation "solely affects centrosome cohesion". "Loss of C-Nap1-mediated centriole cohesion leads to an altered cell migration phenotype". Results and quotations from Floriot et al. (2015).

Hollmann et al. (2017): "Whole genome re-sequencing of one case and four relatives showed a nonsense mutation (g.5995966C>T) in the PZP-like, alpha-2-macroglobulin domain containing 8 (CPAMD8) gene leading to a premature stop codon (CPAMD8 p.Gln74*)".

Whole-genome sequencing of an affected calf and both its parents, followed by filtering of variants, enabled Häfliger et al. (2020) to identify a stop-lost mutation in FGFR3 as the likely causal variant, namely g.116,767,863C>A; NM_174318.3: c.2408G>T; [XM_024992994.1: p.(Ter803Leuext*93), which is "predicted to extend the sequence at the C‐terminal end with 93 additional amino acids". This variant resulted from a de novo mutation in the...

Rothammer et al. (2017): "comparisons of the sequence of [the candidate] haplotype [see Genetic mapping section] with sequence data from four Braunvieh sires and the Aurochs genome identified two possible candidate causal mutations at positions 39,829,806 bp (G/A; R45Q) [omia.variant:847] and 39,864,148 bp (C/T; T444I) [omia.variant:848] that were absent in 1682 animals from various bovine breeds included in the 1000 bull genomes project. Both...

Fontanesi  et al. (2010): "[V]ariation in the white spotting in several cattle breeds is largely influenced by the multiple allelic series at the S locus, which includes at least four alleles (Olson 1999): SH (Hereford pattern), SP (Pinzgauer pattern or lineback), S+ (non-spotted) and s (spotting pattern). The SH allele gives white face, belly, feet and tail, often with a white stripe over the shoulder when homozygous. The SP allele gives pigm...

In a reversal of the normal sequence of discovery, Li et al. (2016) discovered this phenotype AFTER identifying the causal mutation, by noticing that all Belgian Blue cattle with a particular mutation (MLPH: c.87_96del; p.Glu32Aspfs*1), which inactivates MLPH, have an expected dilution phenotype which the authors called "cool gray".

Philipp et al. (2011) reported a "dominantly inherited syndrome associated with hypopigmentation, heterochromia irides, colobomatous eyes and bilateral hearing loss . . . in Fleckvieh cattle"

Reynolds et al. (2021): “The top-associated SNP in these analyses presented a highly correlated … c.1561-1G>A splice acceptor mutation in GALNT2 as potentially responsible for these effects … .” The authors “had provisionally mapped the variant as a candidate stature mutation (unpublished), and subsequently as a variant for which homozygotes were depleted … (Charlier et al., 2016).”

Much useful information on this disorder, including a video, is available from http://www.angus.org/pub/DD/DDInfo.aspx

Jacinto et al. (2025) investigated a Holstein calf with primordial disproportionate dwarfism and craniofacial dysmorphism using a whole genome sequencing approach: "A heterozygous pathogenic missense variant in exon 12 of PDGFRA [Chr6:g.69749162 T > C; c.1685 T > C; p.Ile562Thr; omia.variant:1841], which replaces residue 562, was found and might be due to a spontaneous de novo mutation. However, due to the lack of parental DNA, we could ...

Sartelet et al. (2012) identified the causative mutation as a "c124-­2A>G splice variant in intron 1 of the RNF11 gene". This gene encodes RING finger protein 11, which is a key regulator in the A20 complex of the inflammatory response.