OMIA 001828-9913 : Abortion due to haplotype MH2 in Bos taurus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 608094

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 symbol: MH2

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 MH2, which is located in chromosome BTA29, at 27.9–29.1Mb (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 MH2, Fritz et al. (2013) provided strong evidence for a candidate causal mutation, namely a nonsense mutation (g.28879810C>T; UMD 3.1 genome assembly) in the SLC37A2 gene (which solute carrier family 37, member 2), leading to p.R12X.

Reinartz and Distl (2016) reported homozygosity of this mutant in an aborted Vorderwald x Montbéliarde crossbred foetus inbred to Montbéliarde bulls. The mutant occurs at a frequency of around 5% in Vorderwald cattle with Montbéliarde ancestry but is absent from Vorderwald cattle with no Montbéliarde ancerstry.

Clinical features: The effect of this haplotype is a reduction of 5.26% in heifer calving rate and of 4.85% in cow calving rate (Fritz et al., 2013).

Prevalence: The MH2 haplotype occurs with a frequency of 7.0% in the 16,833 Montbéliarde adult cattle sampled by Fritz et al. (2013), but only once as a homozygote.

Breed: Montbeliarde.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
SLC37A2 solute carrier family 37 (glucose-6-phosphate transporter), member 2 Bos taurus 29 NC_037356.1 (28470045..28523738) SLC37A2 Homologene, Ensembl, NCBI gene

Variants

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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
Montbeliarde Abortion due to haplotype MH2 SLC37A2 nonsense (stop-gain) UMD 3.1 29 g.28879810C>T c.34C>T p.R12* 2013 23762392 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

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.
2016 Reinartz, S., Distl, O. :
Validation of Deleterious Mutations in Vorderwald Cattle. PLoS One 11:e0160013, 2016. Pubmed reference: 27472836. DOI: 10.1371/journal.pone.0160013.
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 14 Jun 2013
  • Changed by Frank Nicholas on 14 Jun 2013
  • Changed by Frank Nicholas on 31 Mar 2014
  • Changed by Frank Nicholas on 04 Aug 2016