Lymphocyte intestinal retention defect, ITGB7-related

Gene: ITGB7

Transmission: Autosomal, recessive (probably)

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, ITGB7 gene; c.904 G>A, p.(Gly375Ser), chromosome 5.

Breed: Holstein

Medical system: Immunologic

Age of onset of symptoms: During adolescence.

To identify genetic patterns that might be responsible for subtle deleterious health phenotypes with incomplete penetration which might be contributing to inbreeding depression, a reverse genetics approach based genetic association studies of almost 400,000 Holstein animals was performed.  Animals that were homozygous for a mutation in the ITGB7 gene were identified for phenotypic studies.  These animals were found to have stunted growth, poor production traits and reduced daily gains compared to controls.  Chronic diarrhea may be an additional feature.  Blood analysis showed increased white blood cell and lymphocyte counts, however, on necropsy, a complete absence of specific T-cells within the lamina propria of the jejunum was observed.  The ITGB7 gene is expressed in intestinal T-cells where it codes for a subunit of an integrin cell adhesion molecule.   This specific integrin molecule is involved in T-cell migration from the blood stream to digestive tissues and thus is an important component of intestinal immunity.  Pedigree analysis revealed that popular sire effects as well as artificial insemination contributed to the dissemination of the ITGB7 mutation within Holstein populations.  Genetic companies and breeders of Holsteins can now use DNA tests to eliminate this mutation from their genetic stock.

References:

OMIA link: [2872-9913]

Inokuma H, Maezawa M, Tahara G, et al. (2025) Retrospective detection of ITGB7 gene mutation in a Holstein calf with chronic diarrhea that was suspected of hereditary cholesterol deficiency. J Vet Med Sci 87:273-276. [pm/39814374]

Leuenberger T, Jacinto JPG, Seefried FR, Drögemüller C. (2024) BLIRD – eine neue genetische Erkrankung beim Holsteinrind in der Schweiz [BLIRD – a new genetic disease in Holstein cattle in Switzerland]. Schweiz Arch Tierheilkd 166:511-518.  [pm/39330956]

Besnard F, Guintard A, Grohs C, Guzylack-Piriou L, et al. (2024) Massive detection of cryptic recessive genetic defects in cattle mining millions of life histories. Genome Biol 25(1):248.  [pm/39343954]

van den Berg I, Nguyen TV, Nguyen TTT, (2024) Imputation accuracy and carrier frequency of deleterious recessive defects in Australian dairy cattle. J Dairy Sci 107:9591-9601.  [pm/38945256]

Contributed by: Kim Cloutier Rattelle and Sierra Mrozinski, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)