OMIA:001901-9913 : Haplotype with homozygous deficiency, RNASEH2B-related in Bos taurus (taurine cattle)

Categories: Mortality / aging (incl. embryonic lethal)

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 610181 (trait) , 610326 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive lethal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2014

Cross-species summary: Phenes previously called ‘Abortion due to halplotype ….. ’ or ‘Abortion (embryonic lethality)’ , have been renamed to ‘Haplotype with homozygous deficiency, …’ or a phene name that is descriptive of the phenotype observed in homozygous affected animals [14/1/2022

Mapping: By conducting a GWAS on 4,072 Holstein-Friesian, 1,177 Jersey, 894 Danish Red, 1,714 Swedish Red, and 2,242 Finnish Ayrshire progeny-tested bulls, each genotyped with the 50K bovine SNP chip (yielding 37,123 informative SNPs across the five breeds), Kadri et al. (2014) identified a QTL for fertility on chromosome BTA12 in Finnish Ayrshires and Swedish Reds. By utilising additional genotyping and whole-genome next-gen sequencing data, these authors were able to attribute the QTL to a 662,463 bp deletion between 20,100,649 to 20,763,116 bp, which "encompasses three protein-encoding genes (RNASEH2B, GUCY1B2 and 3 out of 4 exons of FAM124A), one gene with uncertain coding potential (DLEU7) and two non-coding RNA genes (DLEU7-AS1 and LINC00371)". Mesbah-Uddin et al. (2022) identified the same location: “We performed single-marker association analysis for 8 female fertility traits … in HOL [Holstein], RDC [Nordic Red Dairy cattle], and JER [Jersey] cattle using imputed WGS SNPs, indels, and deletions. … In RDC, 13 deletions reached genome-wide significance; associated phenotypes included 7 fertility traits … . The strongest association was observed for a previously known lethal deletion on chromosome 12 located between position 20,100,648 and 20,763,119 bp ….”

Molecular basis: As reported by Kadri et al. (2014), one of the genes in the deletion (see Mapping section), namely RNASEH2B, is "known to cause embryonic lethality when knocked-out in the mouse". Subsequent investigations confirmed that this deletion is a recessive embryonic lethal in cattle but "is associated with a positive effect on milk yield and composition", which results in selection favouring heterozygotes (balancing selection), thereby maintaining the lethal deletion in the population.

Prevalence: Wu et al. (2020) reported a frequency of 12.9% for the tag haplotype of this recessive lethal effect in 19,309 Nordic Red Dairy cattle.

Breed: Nordic Red (Cattle) (VBO_0016847).
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:

Symbol Description Species Chr Location OMIA gene details page Other Links
RNASEH2B ribonuclease H2 subunit B Bos taurus 12 NC_037339.1 (20346942..20423424) RNASEH2B Homologene, Ensembl , NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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 Year Published PubMed ID(s) Acknowledgements
676 Nordic Red (Cattle) Abortion due to deletion of RNASEH2B RNASEH2B deletion, gross (>20) Naturally occurring variant UMD3.1 12 g.20100648_20763119del A 662kb deletion encompases the gene RNASEH2B, lack of which creates embryonic lethality. 2014 24391517 Genomic position gained from Mesbah-Uddin et al. (2021) - structural variant id esv4015629 (Database of Genomic Variants archive extracted from Ensembl release 94 -

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:001901-9913: Online Mendelian Inheritance in Animals (OMIA) [dataset].


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.
2022 Mesbah-Uddin, M., Guldbrandtsen, B., Capitan, A., Lund, M.S., Boichard, D., Sahana, G. :
Genome-wide association study with imputed whole-genome sequence variants including large deletions for female fertility in 3 Nordic dairy cattle breeds. J Dairy Sci 105:1298-1313, 2022. Pubmed reference: 34955274. DOI: 10.3168/jds.2021-20655.
2021 Derks, M.F.L., Steensma, M. :
Review: Balancing selection for deleterious alleles in livestock. Front Genet 12:761728, 2021. Pubmed reference: 34925454. DOI: 10.3389/fgene.2021.761728.
2020 Wu, X., Mesbah-Uddin, M., Guldbrandtsen, B., Lund, M.S., Sahana, G. :
Novel haplotypes responsible for prenatal death in Nordic Red and Danish Jersey cattle. J Dairy Sci 103:4570-4578, 2020. Pubmed reference: 32197842. DOI: 10.3168/jds.2019-17831.
2014 Kadri, N.K., Sahana, G., Charlier, C., Iso-Touru, T., Guldbrandtsen, B., Karim, L., Nielsen, U.S., Panitz, F., Aamand, G.P., Schulman, N., Georges, M., Vilkki, J., Lund, M.S., Druet, T. :
A 660-kb deletion with antagonistic effects on fertility and milk production segregates at high frequency in nordic red cattle: additional evidence for the common occurrence of balancing selection in livestock. PLoS Genet 10(1):e1004049, 2014. Pubmed reference: 24391517. DOI: 10.1371/journal.pgen.1004049.

Edit History

  • Created by Frank Nicholas on 04 Jan 2014
  • Changed by Frank Nicholas on 04 Jan 2014
  • Changed by Frank Nicholas on 12 Feb 2014
  • Changed by Frank Nicholas on 23 Mar 2020
  • Changed by Imke Tammen2 on 18 Jan 2022
  • Changed by Imke Tammen2 on 29 Jan 2022