Possibly relevant human trait(s) and/or gene(s) (MIM number): 275220

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2012

History: This disorder was first reported (in Galloways) in the UK by Young (1951) and in the USA and Germany by Ojo et a. (1974).

In the 1970s, the Galloway Cattle Society in Great Britain instigated what became a text-book example of how to control a single-locus disorder for which there was (at that time) no blood-based genotype test (Nicholas, 1987). The control programme comprised:

1. Maintaining a register of carriers, i.e. bulls and cows that had produced at least one affected calf

2. An insurance scheme, in which the purchaser of a young bull at any official breed society sale was insured against that young bull throwing affected offspring within 21 months following the sale (9 months gestation and 12 months use). It was compulsory for all younf bulls sold at official sales to be insured, the vendor being obliged to pay the premium.

3. Maintaining a test herd of known carrier cows, through which young bulls could be progeny-tested for this disorder. The effectiveness of this progeny-testing was enhanced by the use of early pregnancy termination, made feasible by the disorder being visible in 90-day embryos (Pollock et al., 1979).

Mapping: Chromosome BTA15

Molecular basis: Deletion: around 45,694 bp including exon 1 of ALX4 of Shorthorns (Beever and Marron, 2012)

Duplication: 20bp duplication in exon 2 of ALX4 of Galloways; g.75154399_75154418dup (AC_000172; UMD3.1), creating a frameshift (Brenig et al., 2015)

Genetic testing: A DNA test for this disorder in Shorthorns was described in 2006 in a patent published in 2012 (Beever and Marron, 2012).

Breeds: Bunaji, Galloway, Shorthorn.

Associated gene: