Phenotypes

Tremors and astasia, as a consequence of hypoplasia of the forelimb-girdle muscles

By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Dennis et al. (2000) identified two causal mutations in Brahman cattle, namely a frameshifting 2-bp deletion (c.1057delTA; the "E7" mutation) and a nonsense mutation (c.1783C>T; p.Arg595Ter; the "E13" mutation) in the bovine GAA gene; and a 2-bp frameshifting deletion (c.2454delCA; the "E18" mutation) in Shorthorns.

The first occurrence of this disorder in any domestic species was reported by Angelos et al. (1995), in Charolais cattle.

Mesbah-Uddin et al. (2019) reported a likely causal variant as a "missense mutation CAD g.72399397T>C (p.Tyr452Cys)"

Besnard et al. (2023) "present a data-mining framework designed to detect recessive defects in livestock that have been previously missed due to a lack of specific signs, incomplete penetrance, or incomplete linkage disequilibrium. This approach leverages the massive data generated by genomic selection. Its basic principle is to compare the observed and expected numbers of homozygotes for sliding haplotypes in animals with different life histo...

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)."

Exome sequencing by Sasaki et al. (2016) within the candidate region (see Mapping section) revealed a likely causal missense variant: g.62382825G > A, p.Pro372Leu) in exon 10 of solute carrier family 12, member 1 (SLC12A1).

By cloning and sequencing a very likely comparative candidate gene (based on the homologous disorder in humans and mice), Pierce et al. (2001) identified a causal mutation as a "a cytidine to adenine transversion at position 156 of the Glra1 gene (156C>A). The 156A allele is predicted to substitute a termination codon for a tyrosine codon (Y24*) in exon 2 . . . This substitution is predicted to result in a prematurely truncated protein that...

Because of the obvious homology of this disorder with the homologous human disorder, Drögemüller et al. (2001) proposed that the bovine disorder be called by the name of its human homologue, which is now done in this catalogue. The earlier names are listed here as species-specific names [Frank Nicholas 20 June 2002].

In a conference abstract, Marron and Beever (2012) reported the causal mutation of hypotrichosis in Belted Galloway cattle to be "an A1684T substitution in exon 9 of hephaestin-like 1 (HEPHL1) resulting in a premature stop codon (K562X)". They further noted that "Hephaestin-like 1 is responsible for copper ion transport. Copper deficiency has been shown to cause anemia, poor immune function, slower growth rates and discolored or poor hair coat...

Murgiano et al. (2015) investigated a family of Pezzata Rossa cattle with 4 affected cows. The pedigree was suggestive of X-linked semi-dominant inheritance with lethality in hemizygous mutant males. Two autosomal segments on chromosome 7 and 14 also showed positive LOD scores in a linkage analysis and could not definitively be excluded. Whole genome sequencing of one affected cow at 28x coverage and comparison to the 1000 bull genomes' sequen...

In the words of Charlier et al. (2008): "a missense mutation in exon 39 (A5804G) resulting in an H1935R substitution in the fourth extracellular loop". The His (normal) form of the peptide is conserved in all vertebrates sequenced to date. (FN 080330) Whole-genome sequencing of the affected Shorthorn calf described by O'Rourke et al. (2017), and subsequent checking for deleterious variants in functional candidate genes, enabled Woolley et al. ...

Häfliger et al. (2020): "Variant calling and filtering against the 1000 Bull Genomes variant catalogue resulted in the detection of a single homozygous protein-changing variant exclusively present in both sequenced genomes. This single-nucleotide deletion in exon 3 of IL17RA on bovine chromosome 5 was predicted to have a deleterious impact on the encoded protein due to a frameshift leading to a truncated gene product."

Braunschweig and Leeb (2006) showed that a "C to A transversion at position 215 bp upstream of the translation initiation site" of the beta-lactoglobulin (LBG) gene segregates with aberrant low expression of beta-lactoglobulin. Other symbols for this gene are BLG and PAEP, the latter being the official NCBI symbol.

Using targeted DNA capture and massively parallel resequencing of the 1.2 Mb region that contained 24 genes, Testoni et al. (2012) identified a causal mutation as a "KDM2B missense mutation (c.2503G>A) leading to an amino acid exchange (p.D835N) in an evolutionary strongly conserved domain". As the same authors report, "The KDM2B gene (also known as JHDM1B and FBXL10) encodes a histone H3 lysine 36 dimethyl (H3K36me2)-specific demethylase ....