Categories: Mortality / aging (incl. embryonic lethal)

Possibly relevant human trait(s) and/or gene(s) (MIM number): 138079 (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: 2022

Inheritance: Pollott et al. (2022): "An initial analysis was undertaken which suggested that there was likely a genetic basis to the disease . . . , and since it was fatal, it could only be inherited as a recessive condition."

Molecular basis: Pollott et al. (2022): "Using whole genome sequencing of only three cases and six carriers, the site of a novel variant causing perinatal mortality in Irish moiled calves was located. Four methods were used to interrogate the variant call format (VCF) data file of these nine animals, they are genotype criteria (GCR), autozygosity-by-difference (ABD), variant prediction scoring, and registered SNP information. From more than nine million variants in the VCF file, only one site was identified by all four methods (Chr4: g.77173487A>T (ARS-UCD1.2 (GCF_002263795.1))." This splice-acceptor variant "was verified on an independent sample of animals from the breed using genotyping by polymerase chain reaction at the candidate site and autozygosity-by-difference using SNP-chips. Both methods confirmed the candidate site."

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

Clinical features: Pollott et al. (2022): "A number of Irish Moiled cattle breeders were concerned about the seemingly high occurrence of early calf deaths in their herds. Affected calves had the following characteristics: days 1–2, the calf appeared slightly hyperactive with more playing/skipping than normal, and may have been seen drinking water from troughs or puddles, and also urinating more frequently than normal. Days 2–4, the calf started to deteriorate and became dull and lethargic. Days 4–6, the calf became dehydrated, very weak, and unable to stand. Death followed soon after. A 2–4 day-old calf was clinically very similar to a calf with septicemia; however, in contrast to septicemic calves, these calves did not respond to antibiotics and fluids given via an intravenous drip. Also when the blood glucose level of such calves was tested levels exceeded 30 mmol/L (Normal = 8 mmol/L). Breeders referred to this condition as “diabetes.”"

Breed: Irish Moiled (Cattle) (VBO_0000246).
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: