Categories: Mortality / aging (incl. embryonic lethal)

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 608865 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive, semi-lethal

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2019

Species-specific name: Haplotype LA2

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 (LA2) is the subject of this entry. Derks et al. (2019) identified a "frameshift mutation in URB1" in the Landrace breed causing embryonic lethality. (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." (Edited by Emmi Payten 24/8/2021)

Molecular basis: Derks et al. (2019) reported the following variant as being likely causal for the embryonic lethality of haplotype LA2: "[a] frameshift mutation in exon 38 of the URB1 gene (13:g.195977038delC) caused by a 1-bp deletion . . . The frameshift (ENSSSCP00000036505:p.Val1961fs) introduces 26 novel amino acids and a premature stop codon, producing a truncated protein of 1,986 amino acids, lacking the final 261 amino acids compared to the wild-type protein (2,247 AA)."

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 15.9%. "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 LA2 as 8.4%, with 2 observed homozygotes (compared with 49.5 expected).

Breed: Landrace (Pig) (VBO_0001161).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: