OMIA:002134-9913 : Haplotype with homozygous deficiency AH2 in Bos taurus (taurine cattle)
Categories: Mortality / aging (incl. embryonic lethal)
Possibly relevant human trait(s) and/or gene(s) (MIM number): 611476 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: 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."
Have human generated variants been created, e.g. through genetic engineering and gene editing
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).
Ayrshire (Cattle) (VBO_0000120).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|RPAP2||RNA polymerase II associated protein 2||Bos taurus||3||NC_037330.1 (51122203..50994696)||RPAP2||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|858||Ayrshire (Cattle)||Abortion due to haplotype AH2||RPAP2||splicing||Naturally occurring variant||3||a splice acceptor variant at 51,267,548 bp [reference sequence not specified] in RPAP2||2017||Reference not in PubMed; see OMIA 002134-9913 for reference details|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2023||Ask-Gullstrand, P., Strandberg, E., Båge, R., Rius-Vilarrasa, E., Berglund, B. :|
|The effect of genetic defects on pregnancy loss in Swedish dairy cattle. J Dairy Sci , 2023. Pubmed reference: 37977438. DOI: 10.3168/jds.2023-24159.|
|2019||Guarini, A.R., Sargolzaei, M., Brito, L.F., Kroezen, V., Lourenco, D.A.L., Baes, C.F., Miglior, F., Cole, J.B., Schenkel, F.S., Guarini, A.R., Sargolzaei, M., Brito, L.F., Kroezen, V., Lourenco, D.A.L., Baes, C.F., Miglior, F., Cole, J.B., Schenkel, F.S. :|
|Estimating the effect of the deleterious recessive haplotypes AH1 and AH2 on reproduction performance of Ayrshire cattle. J Dairy Sci 102:5315-5322, 2019. Pubmed reference: 30954262. DOI: 10.3168/jds.2018-15366.|
|2017||Null, D.J., Hutchison, J.L., Bickhart, D.M., VanRaden, P.M., Cole, J.B. :|
|Discovery of a haplotype affecting fertility in Ayrshire dairy cattle and identification of a putative causal variant. J. Dairy Sci. 100 (Suppl. 2):199 (Abstract 206), 2017.|
- Created by Frank Nicholas on 22 Nov 2017
- Changed by Frank Nicholas on 11 Apr 2019