In other species: chicken , domestic cat , domestic horse , pig , sheep

Categories: Chromosomal phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 147791 (trait)

Single-gene trait/disorder: no

Disease-related: yes

Key variant known: yes

Species summary: Besnard et al. (2023) monitored “sire-family calf mortality within the French and Walloon Holstein populations, and to use this information to detect genetic defects that might have been overlooked by lack of specific symptoms. … After outlining the 5 worst bulls per category, we paid particular attention to the bulls Mo and Pa, because they were half-brothers. Using a battery of approaches, including necropsies, karyotyping, genetic mapping, and whole-genome sequencing, we described 2 new independent genetic defects in their progeny and their molecular etiology. Mo was found to carry a de novo reciprocal translocation between chromosomes BTA26 and BTA29, leading to increased embryonic and juvenile mortality because of aneuploidy. Clinical examination of 2 calves that were monosomic for a large proportion of BTA29, including an orthologous segment deleted in human Jacobsen syndrome, revealed symptoms shared between species.”

Molecular basis: Besnard et al. (2023) "observed a reciprocal translocation between chromosomes BTA26 and BTA29 in Mo [t(26;29)(q11;q19). ... [the authors] demonstrated that 2 affected daughters of Mo with DNA samples available were monosomic for approximately the first 70% of BTA29 ... . Interestingly, comparative genomics revealed synteny between part of the hemizygous region and the monosomy of the telomeric region of chromosome 11q responsible for Jacobsen syndrome."

Clinical features: The bull with the reciprocal translocation "showed normal average volume of ejaculate but low semen quality, with average concentration of semen and fresh and post-freezing motility trait records in the lowest quartile. ... [The bull ranked] as the worst sire for nonreturn rate at 56 d and the fifth worst for conception rate among our cohort of 1,001 Holstein sires. This major degradation of fertility ... is most probably the result of the premature death of a substantial proportion of aneuploid conceptuses throughout the gestation." (Besnard et al., 2023) Of two calves partially monosomic for BTA29 one died at birth, another was euthanatized at 3.5 month of age and a third case had articular defects and difficulties standing. Trisomy of the segment of BTA29 was predicted to lead to embryonic death (Besnard et al., 2023).

Pathology: Pathological findings of animals partially monosomic for BTA29 included tetralogy of Fallot, blind and hypoplastic uterine horn ending with an atrophied and cystic ovary, moderate hypogenesis of the left kidney, abnormally hydrated content in the colon and rectum (Besnard et al., 2023).

Breed: Holstein Friesian (Cattle) (VBO_0000239).
Breeds in which the phene or likely causal variants have been documented. If a likely causal variant has been documented, see variant-specific breed information in the variant table. (Breed information may be incomplete).