OMIA 001827-9913 : Abortion due to haplotype MH1 in Bos taurus
This present OMIA entry is for MH1, which is located in chromosome BTA19, at 27.6–29.4Mb (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 MH1, Fritz et al. (2013) provided strong evidence for a candidate causal mutation, namely a nonsense mutation (g.27956790C>T; UMD 3.1 genome assembly) in the SHBG gene (which encodes sex-hormone binding globulin), leading to p.Q52X.
Reinartz and Distl (2016) reported this mutant occurring in Vorderwald cattle with Montbéliarde ancestry, including in one live animal that is homozygous for this mutant.
The one live animal homozygous for this supposedly lethal variant reported by reported Reinartz and Distl (2016) was reinforced by an extensive study by Michot et al. (2017) who, in the results of genotyping 128,743 Montbéliarde cattle, "identified 242 homozygous carriers for the SHBG nonsense mutation (for 650 expected homozygotes), suggesting that it was not the causative mutation for MH1-linked embryonic lethality." Subsequent fine mapping of the MH1 region excluded SHBG as a candidate and eventually led Michot et al. (2017) to "g.28511199C>T (rs455876205) . . . PFAS p.R1205C" as the likely causal variant. Supporting evidence included "The absence of homozygous mutants among tens of thousands of genotyped animals, the perfect conservation of the affected residue among eukaryotes, and the critical function of PFAS and of the de novo purine synthesis pathway".Clinical features: The effect of this haplotype is a reduction of 5.8% in heifer calving rate and of 4.84% in cow calving rate (Fritz et al., 2013). Prevalence: The MH1 haplotype occurs with a frequency of 9.0% in the 16,833 Montbéliarde adult cattle sampled by Fritz et al. (2013), but never as a homozygote. Breed: Montbeliarde. Associated gene:
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|PFAS||phosphoribosylformylglycinamidine synthase||Bos taurus||19||NC_037346.1 (27879951..27899172)||PFAS||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|
|Montbeliarde||Abortion due to haplotype MH1||PFAS||missense||UMD3.1||19||g.28511199C>T||c.3613C>T||p.R1205C||rs455876205||2017||28803020||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool|
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.
|2017||Michot, P., Fritz, S., Barbat, A., Boussaha, M., Deloche, M.C., Grohs, C., Hoze, C., Le Berre, L., Le Bourhis, D., Desnoes, O., Salvetti, P., Schibler, L., Boichard, D., Capitan, A. :|
|A missense mutation in PFAS (phosphoribosylformylglycinamidine synthase) is likely causal for embryonic lethality associated with the MH1 haplotype in Montbéliarde dairy cattle. J Dairy Sci 100:8176-8187, 2017. Pubmed reference: 28803020. DOI: 10.3168/jds.2017-12579.|
|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.|
- Created by Frank Nicholas on 14 Jun 2013
- Changed by Frank Nicholas on 14 Jun 2013
- Changed by Frank Nicholas on 04 Aug 2016
- Changed by Frank Nicholas on 04 Sep 2017