Categories: Mortality / aging (incl. embryonic lethal) , Embryo phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 607033 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive lethal

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2016

Species-specific name: Haplotype HH5

Species-specific symbol: HH5

Species-specific description: [FN thanks Ekkehard Schütz for feedback on an earlier version of the text on this page]

Mapping: Using a strategy similar to that of VanRaden et al. (2011), Cooper et al. (2013) discovered reduced-fertility haplotype HH5, located on chromosome BTA9. In their table of reduced-fertility haplotypes, Cole et al. (2014) list this haplotype as being located at 92,350,052 – 93,910,957bp on chromosome BTA9. Schütz et al. (2016) fine-mapped the likely causal region of HH5 to be "an approximately 138kb region spanning 93.233Mb to 93.371Mb".

Molecular basis: Schütz et al. (2016) identified the likely causal mutation as "a deletion of 138kbp, spanning position 93,233kb to 93,371kb on chromosome 9 (BTA9), harboring only dimethyl-adenosine transferase 1 (TFB1M). The deletion breakpoints are flanked by bovine long interspersed nuclear elements Bov-B (upstream) and L1ME3 (downstream), suggesting a homologous recombination/deletion event. TFB1M di-methylates adenine residues in the hairpin loop at the 3’-end of mitochondrial 12S rRNA, being essential for synthesis and function of the small ribosomal subunit of mitochondria." The causality of this deletion is reinforced by the fact that homozygous TFB1M knockout mice are not viable and suffer fetal death (Schütz et al., 2016).

Clinical features: Pérez-Gómez et al. (2024) identified that embryos homozugous for the TFB1M variant "are able to develop to early embryonic disc stage but fail to undergo early conceptus elongation, required for pregnancy recognition."

Prevalence: Using direct PCR for the deletion, Schütz et al (2016) estimated the prevalence of carriers to be 5.5% in the interrogated German Holstein population.

Breed: Holstein (black and white) (Cattle) (VBO_0000237).
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: