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

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 of 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. Currently 8.2% of the genotyped US Jersey population 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 the 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 459,784 genotyped Jersey animals. With random mating, about 2,200 affected calves per year with losses of about $250,000 would result from the 1.3 million US Jersey cows in the national population. Selection and mating programs can reduce numbers of JNS-affected births 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.

Adipose gene expression profiles and their associations with adaptations in Northern Finncattle, Mirandesa cattle, Yakutian cattle and Holstein cattle

“…Among Yakutian cattle males, the DEG with the highest log2fold change was GDF5, which is associated with body traits in both Bos taurus and Bos indicus [30]. In Mirandesa cattle females, upregulated genes were associated with latent tuberculosis ( CD209 ) [31], ovarian morphology and milk traits ( ADCY5 ) [43], mastitis and mastitis immunity ( OSMR , PTX3 ) [44,45] and temperament ( BARHL2 ) [32]. In male Mirandesa cattle, the top upregulated genes were linked to immune function ( SLC7A8 ) [33] as well as susceptibility to BSE (PRND) and BVD (DHCR24) [34,35].…”

“…This was followed by UCHL1 and DYNC1I1, which are associated with splayed forelimbs at birth and limb development as well as body conformation traits [44][45][46].…”

Truncation of IFT80 causes early embryonic loss in Holstein cattle associated with Holstein haplotype 2

“…Sequence data from the Animal Genomics and Improvement Laboratory and Collaborative Dairy DNA Repository data sets were aligned to the ARS-UCD1.2 reference genome (Rosen et al, 2020) using BWA-MEM as implemented in bwa version 0.7.15-r1140 (https: / / doi .org/ 10 .48550/ arXiv .1303 .3997) and converted to the binary Sequence Alignment/Map format by samtools version 1.3 (Li et al, 2009). Sequence data variants were identified using the samtools mpileup workflow as described previously (Al-Khudhair et al, 2022). Variants were filtered using version 1.9-259-gb-d769ac of the bcftools "view" command (Li et al, 2009) and the list of filtered variants was annotated using the SNPEff utility (Cingolani et al, 2012) with the Ensembl annotation of the cattle reference genome (version 101).…”

Identification of a putative haplotype associated with recumbency in Holstein calves

“…The rate of inbreeding on both an annual and generational basis increased considerably following the introduction of genomic selection (Dechow et al, 2020;Makanjuola et al, 2020), which has implications for long-term selection response and increases the potential for genetic recessives to emerge (Fritz et al, 2013), or for low frequency mutations to amplify rapidly. For example, a neuropathy associated with splayed forelimbs in Jersey cattle has been recently identified that has increased in frequency from <1% in 2009 to over 8% currently (Al-Khudhair et al, 2022). Genomic testing has accelerated discovery of genetic recessives that result in embryonic mortality (VanRaden et al, 2011b).…”

“…Genetic defects are a prime contributor to neuromuscular disorders in humans and other species ( Laing, 2012 ), and could underlie the problem observed in calves. Additionally, a neuropathy of genetic origin has been recently identified in Jersey cattle ( Al-Khudhair et al, 2022 ). Therefore, the objectives of this study were to conduct a genome-wide association study of affected calves and normal family members to determine if a genetic origin was likely and to establish plausibility of genetic inheritance based on shared ancestors.…”