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

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 600407 (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): :Clinical examination of six homozygous mutant heifers revealed stunted growth, chronic diarrhea with no gross lesions at necropsy, abnormally thin and wavy hair coat, and alopecia of the body extremities ... . Breeders reported that hairless patches appeared after the juvenile molt and peaked in size each winter, suggesting that low temperatures impair hair growth in homozygotes. ... [P]henotypic characterization at the population level revealed reduced birth weight in homozygous mutants supporting in-utero growth retardation, and elevated rates of late juvenile mortality and premature culling ... ." 

Pathology: Besnard et al. (2023): "Histological analysis of shoulder skin samples showed increased hair density and decreased hair diameter in case versus control heifers ... ."

Breed: Normande (Cattle) (VBO_0000322).
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: