OMIA:001830-9913 : Haplotype with homozygous deficiency HH7, CENPU related in Bos taurus
Categories: Mortality / aging (incl. embryonic lethal)
Possibly relevant human trait(s) and/or gene(s) (MIM number): 611511 (gene)
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: 2020
Species-specific symbol: HH7
Mapping: By analysing Illumina Bovine 50k Beadchip genotype data from 47,878 Holstein, 16,833 Montbéliarde and 11,466 Normande cattle in the French genomic selection database, Fritz et al. (2013) identified 34 common (>1%) haplotypes that have a significant deficit (P<10^-4) of homozygotes in live animals, and which are, therefore, each likely to harbour a deleterious mutation. Three of these haplotypes, namely BY (Brachyspina; OMIA 000151-9913), HH1 (OMIA 000001-9913) and HH3 (OMIA 001824-9913), had been reported by VanRaden et al. (2011; J Dairy Sci 94:6153-61). Following the convention of naming such haplotypes with a first letter indicating breed, a second letter H for haplotype, followed by a sequential number, Fritz et al. (2013) named their 14 new Holstein haplotypes as HH4 to HH17, their 11 Montbéliarde haplotypes as MH1 to MH11, and their six Normande haplotypes as NH1 to NH6. Analyses of reproductive data indicated that nine of the 34 haplotypes have a significant effect on fertility, including six of the newly identified haplotypes, namely HH4, HH5, HH6, MH1, MH2 and NH5.
Hozé et al. (2020) reported a new haplotype, also named HH7, located in the BTA27 region 13.0-14.4Mb. (The reason for reusing the haplotype ID HH7 for a haplotype different from the one originally reported is explained by Hozé et al. (2020).)
Molecular basis: Hozé et al. (2020) reported a likely causal variant for the new HH7 haplotype as being "a 4-bp deletion (Chr27 g.14168130_14168133delTACT) that affects a highly conserved region among mammals".
Prevalence: Hozé et al. (2020) "genotyped the candidate variant in 232,775 Holstein individuals and did not observe any homozygotes, whereas 16 were expected (Poisson P-value = 1.1 × 10−7; allele frequency = 0.8%). In addition, genotyping of 250,602 animals from 19 additional breeds revealed that the mutant allele is restricted to animals of Holstein descent."
Breed: Holstein (black and white) (Cattle) (VBO_0000237).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|CENPU||centromere protein U||Bos taurus||27||NC_037354.1 (15165428..15117883)||CENPU||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
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|
|991||Holstein (black and white) (Cattle)||Abortion due to haplotype HH7||CENPU||deletion, small (<=20)||Naturally occurring variant||ARS-UCD1.2||27||g.15123637_15123640del||Hozé et al. (2019): "Considering that CENPU is transcribed in the antisense orientation, this mutation is predicted to result in deletion of the nucleotides located at position +3 to + 6 bp after the splicing donor site of exon 11. Using cross-species nucleotide alignment, we observed that the nucleotide at position +3 is entirely conserved among vertebrates . . . , which suggests that it plays an important role in regulation of CENPU splicing. If modified after exon 11, the abnormal splicing of CENPU could cause mRNA decay or the production of a protein modified after residue 319 out of 409 AA. Based on these factors, we assumed that mutation g.14168130_14168133delTACT on chromosome 27 alters the splicing of CENPU and is embryonic lethal."||2020||31733857|
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||Bengtsson, C., Stålhammar, H., Thomasen, J.R., Fikse, W.F., Strandberg, E., Eriksson, S. :|
|Mating allocations in Holstein combining genomic information and linear programming optimization at the herd level. J Dairy Sci :, 2023. Pubmed reference: 37028963 . DOI: 10.3168/jds.2022-22926.|
|2020||Hozé, C., Escouflaire, C., Mesbah-Uddin, M., Barbat, A., Boussaha, M., Deloche, M.C., Boichard, D., Fritz, S., Capitan, A. :|
|Short communication: A splice site mutation in CENPU is associated with recessive embryonic lethality in Holstein cattle. J Dairy Sci 103:607-612, 2020. Pubmed reference: 31733857 . DOI: 10.3168/jds.2019-17056.|
|2013||Fritz, S., Capitan, A., Djari, A., Rodriguez, S.C., Barbat, A., Baur, A., Grohs, C., Weiss, B., Boussaha, M., Esquerré, D., Klopp, C., Rocha, D., Boichard, D. :|
|Detection of haplotypes associated with prenatal death in dairy cattle and identification of deleterious mutations in GART, SHBG and SLC37A2. PLoS One 8:e65550, 2013. Pubmed reference: 23762392 . DOI: 10.1371/journal.pone.0065550.|
- Created by Frank Nicholas on 14 Jun 2013
- Changed by Frank Nicholas on 14 Jun 2013
- Changed by Frank Nicholas on 27 Apr 2018
- Changed by Frank Nicholas on 19 Nov 2019
- Changed by Frank Nicholas on 14 Mar 2020