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

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 614919 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Probably autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2023

Molecular basis: Besnard et al. (2023) "present a data-mining framework designed to detect recessive defects in livestock that have been previously missed due to a lack of specific signs, incomplete penetrance, or incomplete linkage disequilibrium. This approach leverages the massive data generated by genomic selection. Its basic principle is to compare the observed and expected numbers of homozygotes for sliding haplotypes in animals with different life histories. Within three cattle breeds, we report 33 new loci responsible for increased risk of juvenile mortality and present a series of validations based on large-scale genotyping, clinical examination, and functional studies for candidate variants affecting the NOA1, RFC5, and ITGB7 genes."

Clinical features: Besnard et al. (2023) "estimated that ... 24.4% of the homozygous mutants died during pregnancy ... . An additional 50.7% died before reaching the age of genotyping ... , and the 24.9% that were genotyped died in most cases before one year of age ... . Thus, the eight two- to four-month-old genotyped homozygotes ... that we followed clinically were among the longest-lived. The females developed ill-thrift between three and 12 months of age and were euthanatized for ethical reasons. Hematological and immune analyses revealed neutrophilia ... . In addition, NOA1 mutants showed abnormal blood biochemical parameters suggesting a metabolic disorder and extensive mitochondrial apoptosis ... . Finally, the only homozygous male never showed clinical signs until the end of its follow-up at one year."

Breed: Montbéliarde (Cattle) (VBO_0000306).
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: