OMIA 001836-9913 : Haplotype with homozygous deficiency HH13 in Bos taurus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 604952 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive Lethal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2022

Species-specific symbol: HH13

History: Following recommendations of breed-association staff, Van Raden et al. (2011) identified harmful haplotypes by a sequential identification system comprising "the first letter of the breed name, followed by an “H” for haplotype", followed by sequential numbers. Using this system, they reported haplotypes JH1 (Jersey), HH1, HH2, HH3 (Holstein) and BH1 (Brown Swiss).

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.

Häfliger et al. (2022) reported new Holstein haplotypes HH18-HH38.

Inheritance: Häfliger et al. (2022) reported that "no single homozygous carrier of the . . . KIR2DS1 . . . [variant] was observed neither in the current population of more than 14 thousand Swiss dairy cattle nor in any other breed of cattle included in the 1000 Bull Genomes project".

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.

This present OMIA entry is for HH13, which is located in chromosome BTA18, at 56.4–58.4Mb (UMD 3.1 genome assembly) (Fritz et al., 2013).

Molecular basis: Based on strong evidence obtained in Swiss Holsteins, Häfliger et al (2022) proposed KIR2DS1:p.Gln159* as the likely causal variant for haplotype HH13.

Prevalence: The HH13 haplotype occurs with a frequency of 3.7% in the 47,878 Holstein adult cattle adult sampled by Fritz et al. (2013), but with only 16% of the expected frequency of homozygotes.

Breed: Holstein.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
KIR2DS1 killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 1 Bos taurus 18 NC_037345.1 (62766895..62754403) KIR2DS1 Homologene, Ensembl, NCBI gene

Variants

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 Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
1440 Swiss Holstein Abortion due to haplotype HH13 KIR2DS1 nonsense (stop-gain) Naturally occurring variant ARS-UCD1.2 18 g.62758881G>A c.475C>T p.(Q159*) NM_001097567.1; NP_001091036.1 rs437566778 2022 35361830

References


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.
2022 Häfliger, I.M., Spengeler, M., Seefried, F.R., Drögemüller, C. :
Four novel candidate causal variants for deficient homozygous haplotypes in Holstein cattle. Sci Rep 12:5435, 2022. Pubmed reference: 35361830. DOI: 10.1038/s41598-022-09403-6.
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.
2011 VanRaden, P.M., Olson, K.M., Null, D.J., Hutchison, J.L. :
Harmful recessive effects on fertility detected by absence of homozygous haplotypes. J Dairy Sci 94:6153-61, 2011. Pubmed reference: 22118103. DOI: 10.3168/jds.2011-4624.

Edit History


  • Created by Frank Nicholas on 14 Jun 2013
  • Changed by Frank Nicholas on 14 Jun 2013
  • Changed by Frank Nicholas on 04 Apr 2022