|COLE, JOHN - Former ARS Employee|
|WOLFE, CARI - American Jersey Cattle Association|
|STEFFEN, DAVID - University Of Nebraska|
Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/21/2021
Publication Date: 2/1/2022
Citation: Al-Khudhair, A.S., Null, D.J., Cole, J.B., Wolfe, C.W., Steffen, D.J., Van Raden, P.M. 2022. Inheritance of a mutation causing neuropathy with splayed forelimbs in Jersey cattle. Journal of Dairy Science. 105(2):1338–1345. https://doi.org/10.3168/jds.2021-20600.
Interpretive Summary: A new recessive genetic condition, neuropathy with splayed forelimbs (JNS), has been identified in Jerseys. Calves with JNS are alert at birth but unable to stand, exhibiting neurologic symptoms that include head and neck spasticity and convulsive behavior as well as dislocated shoulders, congenital craniofacial anomalies, and degenerative myelopathy. Pedigree analysis of 16 affected calves identified a common ancestor born in 1995. A haplotype associated with JNS was found on chromosome 6; a missense variant in UCHL1 is believed to be causal. About 6% of genotyped Jerseys are carriers. Haplotype testing can prevent the birth of 300 affected calves annually.
Technical Abstract: A new undesirable genetic factor, neuropathy with splayed forelimbs (JNS), has been identified recently in the Jersey breed. Calves affected with JNS are unable to stand on splayed forelimbs that exhibit significant extensor rigidity and excessive lateral abduction at birth. Affected calves generally are alert at birth but exhibit neurologic symptoms, including spasticity of head and neck and convulsive behavior. Other symptoms reported include dislocated shoulders, congenital craniofacial anomalies, and degenerative myelopathy. Inheritance of an undesirable genetic factor was determined from a study of 16 affected calves reported by Jersey breeders across the United States. All their pedigrees traced back on both paternal and maternal sides to a common ancestor born in 1995. Genotypes revealed that JNS is attributable to a specific haplotype on Bos taurus autosome 6. About 6% of the genotyped Jersey population currently are carriers of the haplotype. Sequencing of the region of shared homozygosity revealed missense variant rs1116058914 at base 60,158,901 of the ARS-UCD1.2 reference map as the most concordant with the genetic condition and most likely cause. The single-base G to A substitution is in the coding region of the last exon of UCHL1, which is conserved across species. Mutations in humans and gene knockouts in mice cause similar recessive symptoms and muscular degeneration. Since December 2020, carrier status has been tracked using the identified haplotype and reported for all 303,087 genotyped Jersey animals. With random mating, about 300 affected calves per year would result from the 360,000 US Jersey cows with records used in national genetic evaluations. Selection and mating programs can reduce the number affected using either the haplotype status or a direct gene test in the future. Breeders should report calf abnormalities to their breed association to help discover new defects such as JNS.