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ARS Home » Northeast Area » Beltsville, Maryland (BARC) » Beltsville Agricultural Research Center » Animal Genomics and Improvement Laboratory » Research » Publications at this Location » Publication #407334
Research Project: Increasing Accuracy of Genomic Prediction, Developing Algorithms, Selecting Markers, and Evaluating New Traits to Improve Dairy Cattle

Location: Animal Genomics and Improvement Laboratory

Title: New mutation within a common haplotype is associated with calf muscle weakness in Holsteins

Author
item Al-Khudhair, Ahmed
item Vanraden, Paul
item Null, Daniel
item Neupane, Mahesh
item MCCLURE, MATTHEW - Abs Global
item DECHOW, CHAD - Pennsylvania State University

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/19/2023
Publication Date: 6/1/2024
Citation: Al-Khudhair, A.S., Van Raden, P.M., Null, D.J., Neupane, M., Mcclure, M.C., Dechow, C.D. 2024. New mutation within a common haplotype is associated with calf muscle weakness in Holsteins. Journal of Dairy Science. 107(6):3768-3779. https://doi.org/10.3168/jds.2023-24121.
DOI: https://doi.org/10.3168/jds.2023-24121

Interpretive Summary: Recently, a genetic component was investigated in newborn calves unable to stand which was termed recumbency and resulted in higher death rates (Dechow et al., 2022). Current research further estimated the effects on heifer livability from national data, traced DNA of the common ancestor back many generations using genotypes of 5.6 million Holsteins, and identified the new mutation causing this condition in a gene affecting muscle movement. Improved pedigree tracking of the DNA and direct genetic tests for the mutation now allow selection and mating programs to reduce the incidence of calf muscle weakness in dairy cattle.

Technical Abstract: A recessive haplotype resulting in elevated calf mortality but with apparent incomplete penetrance was previously linked to the end of chromosome 16 (78.7 to 80.7Mbp). Genotype analysis of 5.6 million Holsteins indicated that the haplotype was common and traced back to 1952 with a key ancestor born in 1984 (HOUSA1964484, Southwind) identified from chip genotypes as homozygous for the suspect haplotype. Sequence data from Southwind, an affected calf, and the sire of the affected calf was scanned for candidate mutations. A missense mutation with a moderate projected impact at 79,613,592 bp was homozygous in the affected calf and heterozygous in the calf’s sire and Southwind. Sequence data available from the Cooperative Dairy DNA Repository for 299 other Holsteins indicated a 97% concordance with the haplotype and an 89% call rate. Exon amino acid sequence appears to be broadly conserved in the CACNA1S gene, and mutations in humans and mice can cause phenotypes of temporary or permanent paralysis analogous to those in calves. Improved methods for using pedigree to track new mutations within existing haplotypes were developed and applied to the haplotypes for both muscle weakness (HMW) and Holstein cholesterol deficiency (HCD). For HCD, concordance of the gene test with its haplotype status was greatly improved. For both defects, haplotype status was matched to heifer livability records for 558K calves. For HMW, only 46 heifers with livability records were homozygous and traced only to Southwind on both sides. Of those, 52% of those died before 18 months at an average age of 1.7+-1.6 months, but that death rate may be underestimated if only healthier calves were genotyped. The death rate was 2.4% for noncarriers. Different reporting methods or dominance effects may be needed to include HMW and other partially lethal effects in selection and mating. Direct tests are needed for new mutations within existing common haplotypes because tracking can be difficult even with accurate pedigrees when the original 4 haplotype has high frequency.