BLAD (Bovine Leucocyte Adhesion Deficiency)

 

Gene: ITGB2 (Integrin subunit beta 2, previously named CD18)

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, ITGB2; c.383A>G, exon 3, p.(D128G), bovine chromosome 1.

Breed: Holstein

Medical system: Immune

Age of onset of symptoms: symptoms can become evident soon after birth.

Bovine Leukocyte Adhesion Deficiency (BLAD) is a genetic disease seen in Holstein cows that results in an inability of immune cells to pass from the inside of blood vessels into tissues. This is caused by a deficiency in a white blood cell membrane adhesion protein called beta 2 integrin. This in turn results in the affected animal being very susceptible to bacterial infections, in delayed wound healing, poor growth and ultimately premature death.

Clinical signs for homozygous mutated animals (with two copies of the mutation) can include, among others, a reduction of neutrophils in the blood (neutropenia), ulcers on the oral mucosa, severe periodontitis, loss of teeth, anorexia, fever, chronic pneumonia, and recurrent diarrhea.  In 1993 the percentage of Holsteins born with FDALW in the United States was 0.2%.  DNA testing to identify carrier animals and careful breeding choices have effectively eliminated the mutation and disease from the genetics of Holstein cattle.

 

References:

OMIA link: [0595-9913]

Bengtsson C, Stålhammar H, Thomasen JR, et al. (2023) Mating allocations in Holstein combining genomic information and linear programming optimization at the herd level. J Dairy Sci 106(5):3359-3375   [pubmed/37028963]

Caivio-Nasner S, López-Herrera A, González-Herrera LG, Rincón JC. (2021) Frequency of genotypic markers for genetic disorders, colour, polledness, and major genes in Blanco Orejinegro cattle. Trop Anim Health Prod 53:546. [pubmed/34779908]

Alyethodi RR, Singh U, Kumar S, et al. (2016) Development of a fast and economical genotyping protocol for bovine leukocyte adhesion deficiency (BLAD) in cattle. Springerplus 5:1442. [pubmed/27652018]

Nagahata H. (2004) Bovine leukocyte adhesion deficiency (BLAD): a review. J Vet Med Sci 66:1475-82. [pubmed/15644595]

Gerardi AS. (1996) Bovine leucocyte adhesion deficiency – a review of a modern disease and its implications. Research in Veterinary Science 61:183-186. [pubmed/9838844]

Gilbert RO, Rebhun WC, Kim CA, Kehrli, et al. (1993) Clinical Manifestations of Leukocyte Adhesion Deficiency in Cattle – 14 Cases (1977-1991). JAVMA 202:445-449.  [pubmed/8095042]

Shuster DE, Kehrli ME, Ackermann MR, Gilbert RO. (1992) Identification and Prevalence of a Genetic Defect That Causes Leukocyte Adhesion Deficiency in Holstein Cattle. PNAS 89:9225-9229.  [pubmed/1384046]

 

Contributed by Dr. Anaïs Fournier-Leclaire, Class of 2023, Faculté de médecine vétérinaire, Université de Montréal.   (Translation DWS).