Categories: Mortality / aging (incl. embryonic lethal)

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 609728 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2021

Species-specific description: Häfliger et al. (2021) investigated “the two Braunvieh populations reared in Switzerland, the dairy Brown Swiss (BS) and the dual-purpose Original Braunvieh (OB). We performed a genome-wide analysis of array data of trios (sire, dam, and offspring) from the routine genomic selection to identify candidate regions showing missing homozygosity and phenotypic associations with five fertility, ten birth, and nine growth-related traits. In addition, genome-wide single SNP regression studies based on 114,890 single nucleotide polymorphisms (SNPs) for each of the two populations were performed. Furthermore, whole-genome sequencing data of 430 cattle including 70 putative haplotype carriers were mined to identify potential candidate variants that were validated by genotyping the current population using a custom array. … Using a trio-based approach, we identified 38 haplotype regions for BS and five for OB … . For the BS population, we confirmed two known haplotypes, BH1 and BH2 [OMIA 001825-9913 and OMIA 001939-9913]. Twenty-four variants that potentially explained the missing homozygosity and associated traits were detected …. We propose a list of six protein-changing variants as potentially causing missing homozygosity. These variants need to be functionally validated and incorporated in the breeding program.” Information about the BH6 haplotype is described in this entry.

Mapping: Häfliger et al. (2021) “The BS dataset included 48,807 genotyped animals, with 14,450 trios [trio: sire, dam, and offspring]." The BH6 haplotype was mapped to Chr2:86065338-87460373 (ARSUCD1.2)

Molecular basis: Häfliger et al. (2021) “Whole-genome sequencing data of 430 cattle including 70 putative haplotype carriers were mined to identify potential candidate variants that were validated by genotyping the current population using a custom array.” BH6 Haplotype: MARS2, chr2:86191230, NM_001098971.1, c.1553G>A, p.Arg518Gln

Breed: Brown Swiss (Cattle) (VBO_0000166).
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: