Identification and prevalence of a genetic defect that causes leukocyte adhesion deficiency in Holstein cattle.

TLDR

Leukocyte adhesion deficiency caused by a D128G mutation in CD18 is widespread in Holstein cattle worldwide, making it one of the most common genetic diseases in animal agriculture, with all affected animals tracing back to a single bull used in artificial insemination. The study aims to develop a diagnostic test and organizational strategy to enable nearly complete eradication of bovine LAD within one year. The authors identified two point mutations in bovine CD18, including a D128G substitution in the extracellular domain, and confirmed that all clinically affected calves and additional cases were homozygous for this allele through DNA testing. The D128G allele has a carrier frequency of ~15% in bulls and 6% in cows, and the study confirms that bovine LAD is genetically and phenotypically analogous to human LAD, providing a valuable animal model.

Abstract

Two point mutations were identified within the gene encoding bovine CD18 in a Holstein calf afflicted with leukocyte adhesion deficiency (LAD). One mutation causes an aspartic acid to glycine substitution at amino acid 128 (D128G) in the highly conserved extracellular region of this adhesion glycoprotein, a region where several mutations have been found to cause human LAD. The other mutation is silent. Twenty calves with clinical symptoms of LAD were tested, and all were homozygous for the D128G allele. In addition, two calves homozygous for the D128G allele were identified during widespread DNA testing, and both were subsequently found to exhibit symptoms of LAD. The carrier frequency for the D128G allele among Holstein cattle in the United States is approximately 15% among bulls and 6% among cows. This mutation is also prevalent among Holstein cattle throughout the world, placing this disorder among the most common genetic diseases known in animal agriculture. All cattle with the mutant allele are related to one bull, who through the use of artificial insemination sired many calves in the 1950s and 1960s. The organization of the dairy industry and the diagnostic test described herein will enable nearly complete eradication of bovine LAD within 1 year. These results also demonstrate that bovine LAD is genetically homologous and phenotypically similar to human LAD, thus providing a useful animal model for studies of LAD and beta 2 integrin function.