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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 #402359
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: Candidate mutation for calf recumbency in Holsteins

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

Submitted to: Journal of Dairy Science
Publication Type: Abstract Only
Publication Acceptance Date: 3/21/2023
Publication Date: 6/21/2023
Citation: Dechow, C., VanRaden, P.M., Null, D.J., Al-Khudhair, A.S., McClure, M. 2023. Candidate mutation for calf recumbency in Holsteins [abstract]. Journal of Dairy Science. 106(Suppl. 1):52-53(abstr. 2245).

Interpretive Summary:

Technical Abstract: A recessive recumbency haplotype that results in elevated calf mortality but with apparent incomplete penetrance was previously linked to the end of chromosome 16 (78.7 to 80.7Mbp). The region included 110 unique genes, 13 of which were plausible candidate genes based on association with diseases reported in the Online Mendelian Inheritance in Man database. Genotype analysis 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 (30x, Illumina HiSeq pair-ended) from Southwind, an affected calf, and the sire of the affected calf was scanned for candidate mutations. A missense mutation in calcium channel, voltage-dependent, L type, alpha 1S subunit (CACNA1S) that alters a GGC codon to AGC and facilitates a glycine to serine amino acid substitution at 79,613,592 bp was considered the most promising candidate. The mutation was homozygous in the affected calf and heterozygous in the calf’s sire and Southwind. Sequence data available from the Cooperative Dairy DNA for 299 other Holsteins indicated a 97% concordance with the haplotype and an 89% call rate. The Sorting Intolerant From Tolerant score (range 0 to 0.01) indicated that the mutation was deleterious with a moderate projected impact which may explain the incomplete penetrance. CACNA1S is predicted to have multiple transcripts of 39 to 40 exons with the mutation in exon 30 to 32; the exon amino acid sequence appears to be broadly conserved. CACNA1S enables calcium channel voltage gate activity and is highly expressed in skeletal muscle. In humans, heterozygotes for a CACNA1S mutation may experience periodic paralysis whereas homozygotes may have no ability to stand and can be more severely affected than the recumbency. Mice homozygous for CACNA1S knockout mutations show degenerated muscles, edema, failure of myoblast differentiation by day 13 of embryonic development, and perinatal death. A stand-alone test for the mutation is under development and the mutation is expected to be added to a genotyping array.