Categories: Mortality / aging (incl. embryonic lethal)

Possibly relevant human trait(s) and/or gene(s) (MIM number): 611511 (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: 2020

Species-specific symbol: HH7

Mapping: By analysing Illumina Bovine 50k Beadchip genotype data from 47,878 Holstein, 16,833 Montbéliarde and 11,466 Normande cattle in the French genomic selection database, Fritz et al. (2013) identified 34 common (>1%) haplotypes that have a significant deficit (P<10^-4) of homozygotes in live animals, and which are, therefore, each likely to harbour a deleterious mutation. Three of these haplotypes, namely BY (Brachyspina; OMIA 000151-9913), HH1 (OMIA 000001-9913) and HH3 (OMIA 001824-9913), had been reported by VanRaden et al. (2011; J Dairy Sci 94:6153-61). Following the convention of naming such haplotypes with a first letter indicating breed, a second letter H for haplotype, followed by a sequential number, Fritz et al. (2013) named their 14 new Holstein haplotypes as HH4 to HH17, their 11 Montbéliarde haplotypes as MH1 to MH11, and their six Normande haplotypes as NH1 to NH6. Analyses of reproductive data indicated that nine of the 34 haplotypes have a significant effect on fertility, including six of the newly identified haplotypes, namely HH4, HH5, HH6, MH1, MH2 and NH5. Hozé et al. (2020) reported a new haplotype, also named HH7, located in the BTA27 region 13.0-14.4Mb. (The reason for reusing the haplotype ID HH7 for a haplotype different from the one originally reported is explained by Hozé et al. (2020).)

Molecular basis: Hozé et al. (2020) reported a likely causal variant for the new HH7 haplotype as being "a 4-bp deletion (Chr27 g.14168130_14168133delTACT) that affects a highly conserved region among mammals".

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Prevalence: Hozé et al. (2020) "genotyped the candidate variant in 232,775 Holstein individuals and did not observe any homozygotes, whereas 16 were expected (Poisson P-value = 1.1 × 10−7; allele frequency = 0.8%). In addition, genotyping of 250,602 animals from 19 additional breeds revealed that the mutant allele is restricted to animals of Holstein descent."

Breed: Holstein (black and white) (Cattle) (VBO_0000237).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: