# Bovine Lymphocyte Intestinal Retention Defect (BLIRD): a novel recessive immunogenetic disorder in Holstein cattle

## TL;DR

A new genetic disorder in Holstein cattle, caused by a mutation in the ITGB7 gene, leads to shorter lifespan and poor health in affected animals.

## Contribution

Identification of a novel recessive immunogenetic disorder (BLIRD) in Holstein cattle caused by the ITGB7 p.G375S mutation.

## Key findings

- Homozygous carriers of the ITGB7 p.G375S mutation had a significantly shorter lifespan and reduced body weight and dairy performance.
- The mutation caused lymphocytic leucocytosis, eosinophilia, and changes in faecal microbiota.
- The blood profile can help identify carriers with poor growth and health.

## Abstract

Dozens of missed recessive loci affecting homozygous carriers’ life expectancy were recently reported. This article details the clinical, biological and pathological manifestations of a new bovine genetic disorder caused by the ITGB7 p.G375S point mutation in the French Holstein cattle breed (BLIRD: OMIA:002872–9913). Our thorough study involved database analysis of genotyped cattle and a series of case-control investigations of forty individuals homozygous for the causative variant. These variant homozygotes had a significantly shorter lifespan (fewer than 64% surviving past three years vs. 87% in control), along with reduced body weight, daily weight gain, and dairy performance. The mutation did not affect most biochemical parameters, but a marked lymphocytic leucocytosis, moderate eosinophilia and differences in faecal microbiota were observed. Although non-pathognomonic symptoms may be confused with those of common environmental diseases, the blood profile effectively identified suspected carriers who developed ill-thrift and poor growth as heifers. Our research demonstrates that the bovine ITGB7 p.G375S substitution leads to reduced longevity, poor condition and production in most homozygous carriers. Furthermore, this spontaneous model may help to refine the functions of the integrin β7 (ITGB7) in immune homeostasis and defence.