OMIA 001826-9913 : Abortion due to haplotype HH4 in Bos taurus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 138440

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive Lethal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2013

Species-specific name: Haplotype HH4

Species-specific symbol: HH4

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 HH4, which is located in chromosome BTA1, at 1.9-3.3Mb (UMD 3.1 genome assembly) (Fritz et al., 2013).

Molecular basis: For eight of the nine haplotypes with a significant effect on calving rate (see Mapping section), Fritz et al. (2013) searched for causal mutations via whole-genome sequence data from 25 Holstein, 11 Montbéliarde and nine Normande bulls which had made major contributions to their breed. Specifically, they filtered "for mutations that were (a) located at+or –6 Mb from the detected haplotype (b) carried in the heterozygous state by the carrier bulls and (c) absent from the non carrier bulls from the three breeds" and then examined identified polymorphisms for their likely effect on protein structure and function. For HH4, Fritz et al. (2013) provided convincing evidence for a candidate causal mutation, namely a missense mutation (g.1277227A.C; UMD 3.1 genome assembly) in the GART gene (which encodes glycinamide ribonucleotide transformylase), leading to p.N290T.

Clinical features: The effect of this haplotype is a reduction of 5.8% in heifer calving rate and of 1.74% in cow calving rate (Fritz et al., 2013).

Prevalence: The HH4 haplotype occurs with a frequency of 3.6% in the 47,878 Holstein adult cattle sampled by Fritz et al. (2013), but never as a homozygote.

Breed: Holstein.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
GART phosphoribosylglycinamide formyltransferase, phosphoribosylglycinamide synthetase, phosphoribosylaminoimidazole synthetase Bos taurus 1 NC_037328.1 (1986098..2012388) GART 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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Holstein Abortion due to haplotype HH4 GART missense UMD3.1 1 g.1277227A>C c.869A>C p.N290T rs465495560 2013 23762392 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool; Breed information kindly provided or confirmed by Matt McClure and Jennifer McClure from "Understanding Genetics and Complete Genetic Disease and Trait Definition (Expanded 2016 Edition)" (


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.
2016 Cole, J.B., Null, D.J., VanRaden, P.M. :
Phenotypic and genetic effects of recessive haplotypes on yield, longevity, and fertility. J Dairy Sci 99:7274-88, 2016. Pubmed reference: 27394947. DOI: 10.3168/jds.2015-10777.
Segelke, D., Täubert, H., Reinhardt, F., Thaller, G. :
Considering genetic characteristics in German Holstein breeding programs. J Dairy Sci 99:458-67, 2016. Pubmed reference: 26601581. DOI: 10.3168/jds.2015-9764.
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.

Edit History

  • Created by Frank Nicholas on 12 Jun 2013
  • Changed by Frank Nicholas on 12 Jun 2013
  • Changed by Frank Nicholas on 14 Jun 2013
  • Changed by Frank Nicholas on 24 Mar 2015