OMIA 002181-9823 : Abortion, POLR1B-related in Sus scrofa

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 602000 (gene) , 618939 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive Lethal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2019

Species-specific name: Haplotype LA1

Species-specific description: Derks et al. (2019) identified five relatively frequent haplotypes for which there was either a deficit or a complete lack of homozygotes in large populations of Landrace (28,085) and Duroc (11,255). One of the four Landrace haplotypes (LA1) is the subject of this entry. Derks et al. (2019) identified that a "splice region mutation in POLR1B induces early embryonic lethality in Landrace [pigs]". LA1 carriers showed "increased mothering ability ... increased carcass quality ... lower meat quality ... [and] slower growth" compared to non-carriers. (Edited by Emmi Payten 24/8/2021)

History: This haplotype was first identified in two commercial pig populations in Norway (Derks et al., 2019). (Edited by Emmi Payten 24/8/2021)

Mapping: Derks et al. (2019): "To identify lethal alleles segregating in the pig populations we examined genotype data from 28,085 (Landrace), and 11,255 (Duroc) animals. All animals were genotyped or imputed to a medium-density 50K SNPchip ... . The genotypes were phased to build haplotypes, and then we applied an overlapping sliding window approach to identify haplotypes that show a deficit in homozygosity ... . The analysis yielded one strong candidate haplotype (DU1) harbouring a lethal recessive allele in the Duroc population, and four candidates in the Landrace population (LA1-4), respectively." Derks et al. (2019) performed a fine-mapping analysis of wild-type haplotypes for LA1 carrier animals to identify recombinant individuals. The LA1 haplotype was divided into 5 sub-haplotypes, 1Mb in length and each was investigated to determine whether any were in the homozygous state. "Homozygous sub-haplotypes were excluded to carry the causal mutation". (Edited by Emmi Payten 24/8/2021)

Molecular basis: Derks et al. (2019): A "splice mutation affects a conserved adenine in the GTRAG splice site motif (positive strand: 3:g.43952776T>G. ... the splice region mutation causes exon skipping of exon 14 ... . Skipping of exon 14 introduces a glutamic acid and a premature stop codon in the second codon of the terminal exon, lacking the final 370 amino acids located in the conserved subunit 2, hybrid-binding domain (binding to the DNA strand) ... Hence, this splice-region mutation likely causes a complete LoF [loss of function] of the POLR1B protein."

Clinical features: Derks et al. (2019) "analysed the effect of the haplotypes on fertility phenotypes including total number born (TNB), number born alive (NBA), number of stillborn (NSB), and number of mummified piglets (MUM)." The reduction in litter size (total number born) in carrier x carrier matings, compared with carrier x non-carrier matings, was 18.8%. "No significant increase in number of stillborn (NSB) or mummified piglets (MUM) was found, suggesting that homozygotes die very early in pregnancy." (Edited by Emmi Payten 24/8/2021)

Prevalence: Derks et al. (2019) reported the carrier frequency of haplotype LA1 as 13.4%, with zero observed homozygotes.

Breed: Landrace.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
POLR1B polymerase (RNA) I polypeptide B, 128kDa Sus scrofa 3 NC_010445.4 (43974283..43949032) POLR1B Homologene, Ensembl, NCBI gene

Variants

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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.

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
1052 Landrace Embryonic lethality POLR1B splicing Naturally occurring variant Sscrofa11.1 3 g.43952776T>G Derks et al. (2019): "Skipping of exon 14 introduces a glutamic acid and a premature stop codon in the second codon of the terminal exon, lacking the final 370 amino acids located in the conserved subunit 2, hybrid-binding domain (binding to the DNA strand)" 2019 30875370

Reference


2019 Derks, M.F.L., Gjuvsland, A.B., Bosse, M., Lopes, M.S., van Son, M., Harlizius, B., Tan, B.F., Hamland, H., Grindflek, E., Groenen, M.A.M., Megens, H.J., Derks, M.F.L., Gjuvsland, A.B., Bosse, M., Lopes, M.S., van Son, M., Harlizius, B., Tan, B.F., Hamland, H., Grindflek, E., Groenen, M.A.M., Megens, H.J. :
Loss of function mutations in essential genes cause embryonic lethality in pigs. PLoS Genet 15:e1008055, 2019. Pubmed reference: 30875370. DOI: 10.1371/journal.pgen.1008055.

Edit History


  • Created by Frank Nicholas on 25 Mar 2019
  • Changed by Frank Nicholas on 25 Mar 2019
  • Changed by Frank Nicholas on 26 Mar 2019
  • Changed by Imke Tammen2 on 27 May 2021
  • Changed by Imke Tammen2 on 24 Aug 2021