Identification of a putative haplotype associated with recumbency in Holstein calves

Thirty-four Holstein calves from multiple farms were found recumbent during the neonatal period with no detectable neurologic, infectious, or metabolic abnormalities. Most calves did not survive beyond 6 wk of age. The objective of this study was to conduct a genome-wide association and pedigree analysis to determine if a genetic origin was plausible. There were 101,917 DNA markers for 18 affected calves and 26 unaffected family controls available for analysis. Genome-wide association, homozygosity screening, and a parental based transmission disequilibrium test were conducted in PLINK. A genomic region on the end of chromosome 16 that contained 78 markers based on a recessive inheritance model and that spanned 5.1 million bp was considered the most probable region for a genetic defect; the region was narrowed to 2.1 million bp following homozygosity screening and the transmission disequilibrium test with all affected calves homozygous in the candidate region and 1 homozygous control. A genotyped sire and 2 dams with imputed genotypes were heterozygous in the candidate region. A common sire born in 2008 was identified that was present for both paternal and maternal lineages of all affected calves; nearly all lineages traced through a prolific son born in 2010 who was genotyped and was heterozygous for the candidate region. Therefore, a possible genetic defect with incomplete penetrance on chromosome 16 that results in recumbency has been identified. Further efforts with an increase in families represented are needed to confirm a genetic basis, and identify the mutation and mode of inheritance.