Categories: Mortality / aging (incl. embryonic lethal)

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 615986 (trait) , 608022 (trait) , 608699 (gene) , 607968 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive lethal

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2018

Species-specific name: SSC18 haplotype

Species-specific description: Derks et al. (2018) describe "a lethal 212kb deletion with pleiotropic effects on two different genes, one resulting in fetal death in homozygous state (BMPER), and the other increasing growth (BBS9) in heterozygous state. We provide strong evidence for balancing selection resulting in an unexpected high frequency of a lethal allele in the population."

Mapping: Derks et al. (2018) analysed a population of 23,722 purebred Large White pigs to identify lethal alleles. "The animals were genotyped on the Illumina GeneSeek custom 50K SNPchip." To identify the missing homozygote haplotypes, "the SS18 haplotype [was tested] for the expected number of homozygotes using both parents haplotype information." (Edited by Emmi Payten 24/8/2021)

Molecular basis: Derks et al. (2018) identified "a recessive lethal deletion of 212kb (del) within the BBS9 gene in a breeding population of pigs. ... The mutant transcript results in a frameshift introducing 11 novel amino acids before a premature stop codon, generating a truncated BBS9 protein ...[and reduces] expression of the downstream BMPER gene, an essential gene for normal foetal development." (Edited by Emmi Payten 24/8/2021)

Clinical features: Derks et al. (2018): "Homozygous del/del animals die mid- to late-gestation, as observed from high increase in numbers of mummified piglets resulting from carrier-by-carrier crosses. ...heterozygous carriers exhibit increased growth rate, an important selection trait in pig breeding. Increased growth and appetite together with a lower birth weight for carriers of the BBS9 null allele in pigs is analogous to the phenotype described in human and mouse for (naturally occurring) BBS9 null-mutants."

Prevalence: Derks et al. (2018) estimated a 10.8% carrier frequency (5.4% allele frequency) in the Large White population studied. There were no homozygous individuals identified in the population. The authors traced the origin of the deletion in the population over a 12 year period (2006-2018). The carrier frequency was high (>15%) from 2006-2010 and then stabilised from 2012 onwards (~10%). (Edited by Emmi Payten 24/8/2021)

Breed: Large White (Pig) (VBO_0001163).

Associated genes: