Categories: Mortality / aging (incl. embryonic lethal)

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 611476 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2017

History: Details of the first Ayrshire lethal haplotype (AH1) are presented in OMIA 001934-9913. Null et al. (2017) reported that "A second [Ayrshire] haplotype [AH2] reached the threshold for statistical significance (7 expected homozygotes and none observed) in October 2013. Sire conception rate was 6.1% lower for matings of carrier sires to cows with carrier maternal grandsires, but the effect was not significant. As of December 2016, 23.5 homozygotes were expected but none had been observed."

Molecular basis: Null et al. (2017): "A splice acceptor variant at 51,267,548 bp in the RNA Polymerase 2 Associated Protein (RPAP2) gene was the most likely causal variant in the [AH2] haplotype. RPAP2 is an essential component of the RNA polymerase 2 holoenzyme necessary for transcription of snRNA species. Experiments with mouse knockouts also found a deficiency of homozygotes, suggesting that RPAP2 is necessary for embryonic development."

Prevalence: Null et al. (2017) reported that the frequency of the AH2 haplotype in US Ayrshires "has increased from 6% in animals born in 1990 to 21.7% for animals born since 2008." Guarini et al. (2019) reported the frequency of the AH2 haplotype in Canadian Ayrshires was less than 1% from 1997 to 2010 after which it rose to be around 11.2% in 2014 (estimated from their Figure 2).

Breed: Ayrshire (Cattle) (VBO_0000120).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: