Communication Dans Un Congrès Année : 2023

Description of a new point mutation in ITGB7 affecting life expectancy in Holstein dairy cattle

Résumé

Objectives: As a result of intensive genetic selection, bovine dairy breeds show high consanguinity trends. This leads to an increase in health problems, a reduction in life expectancy and an elevated juvenile mortality rate. We hypothesized that inbreeding, i.e. homozygosity at one or more allelic loci, is responsible for the decline of fitness. Searching for enrichment or depletion in homozygous haplotypes in groups of animals with different life trajectories (HHED mapping), we identified several new recessive genetic defects affecting longevity in French Holstein cattle. The purpose of our study is to determine the pathophysiology of one of them, caused by a deleterious substitution in ITGB7. Materials and methods: To characterize the consequences of this point mutation on bovine health, clinical signs and associated lesions were recorded in a series of case and control animals genotyped for this mutation as part of routine genomic evaluation. During the epidemiological study, homozygous mutant females were studied with matched heterozygous and wild-type controls. Clinical records (weight, size, ADG, BCS, fertility, milk production, …) as well as environmental factors (housing, livestock management) were analysed for a total of 25 cases. Blood and faecal samples were collected to describe the biological consequences of the point mutation (haematology, biochemistry, parasitology, faecal microbiota, biochemistry, …). Then, based on the basic knowledge of protein function, we carried out a case/control study in a small number of cattle to further investigate the differences between homozygous mutant and wild-type individuals and to determine altered functions at the organ and system levels. Post-mortem examination was also undertaken for identification of gross lesions and microscopic examination was done on various tissue samples. Single-cell RNA-sequencing of mononuclear cells from various tissues like blood, lymph node and intestine is underway. Outcomes: The lifespan of homozygous mutants was significantly reduced, and two periods of elevated mortality rate were identified (exponential growth phase, and early lactation). On average, affected animals were shorter, lighter and had lower performances (such as ADG). On the other hand, most biochemical parameters were not affected by the presence of the mutation, but a marked lymphocytic leucocytosis and moderate eosinophilia were identified that may serve as phenotypic traits to identify carriers in the non-genotyped population. Histopathology of the lymphoreticular system and immunological studies are in progress to specify the mechanisms involved at the cellular and molecular levels. Due to the protein function, the disease was named BLIRD for Bovine Lymphocyte Intestinal Retention Default. Conclusions: We show that an inherited mutation leads to ill-thrift and increased mortality in Holstein dairy cattle. Non-pathognomonic symptoms may be confused with those of common diseases of environmental origin, but the haematological profile is sufficient to detect suspected carriers.

Fichier non déposé

Dates et versions

hal-04726395 , version 1 (08-10-2024)

Identifiants

  • HAL Id : hal-04726395 , version 1

Citer

Lucie Dutheil, Laurence Guzylack-Piriou, Blandine Gaussères, Adèle Clément, Florian Besnard, et al.. Description of a new point mutation in ITGB7 affecting life expectancy in Holstein dairy cattle. European Buiatrics Congress, Aug 2023, Berlin, Germany. ⟨hal-04726395⟩
200 Consultations
0 Téléchargements

Partager

  • More