Inheritance of a mutation causing neuropathy with splayed forelimbs in Jersey cattle

Area of Science:

• Animal Genetics
• Veterinary Medicine
• Dairying

Background:

• A novel genetic disorder, neuropathy with splayed forelimbs (JNS), has been identified in the Jersey cattle breed.
• Affected calves exhibit severe congenital abnormalities including splayed forelimbs, spasticity, and neurological deficits.

Purpose of the Study:

• To identify the genetic basis of JNS in Jersey cattle.
• To determine the inheritance pattern and prevalence of the JNS genetic factor.

Main Methods:

• Pedigree analysis of 16 affected calves traced the defect to a common ancestor.
• Genotyping identified a specific haplotype on Bos taurus autosome 6 associated with JNS.
• Sequencing revealed a missense variant (rs1116058914) in the UCHL1 gene as the likely causative mutation.

Main Results:

• The JNS defect is inherited recessively and linked to a specific haplotype on chromosome 6.
• Approximately 8.2% of genotyped US Jersey cattle are carriers of the JNS haplotype.
• The causative mutation is a G-to-A substitution in the UCHL1 gene, conserved across species.

Conclusions:

• The identified genetic variant in UCHL1 is the most probable cause of JNS.
• Current carrier frequency suggests significant annual losses in the US Jersey population without intervention.
• Genetic testing and selective breeding programs can mitigate the incidence of JNS-affected calves.