OMIA:001901-9913 : Haplotype with homozygous deficiency, RNASEH2B-related in Bos taurus (taurine cattle)
Categories: Mortality / aging (incl. embryonic lethal)
Links to MONDO diseases: No links.
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.
Have human generated variants been created, e.g. through genetic engineering and gene editing
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.
Nordic Red (Cattle) (VBO_0016847).
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|
|RNASEH2B||ribonuclease H2 subunit B||Bos taurus||12||NC_037339.1 (20346942..20423424)||RNASEH2B||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|
|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 - http://ftp.ensembl.org/pub/release-94/).|
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.|
|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.|
- Created by Frank Nicholas on 04 Jan 2014
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