Fig. 5

Characterization of the ITGB7 substitution. a (top) Modeling of the 3D structure of the ITGα4β7 heterodimer using crystallography in humans, and evaluation of the consequences of glycine to serine substitution at amino acid position 283 in humans (375 in bovine). The purple dashed lines illustrate the clash with a predicted 0.8 kcal/mol reduction in binding affinity (see “Methods” for further details). a (down) WebLogo representation of multiple protein alignments showing perfect conservation of the mutated glycine residue among 128 vertebrate ITGB7 orthologs (Additional file 1: Table S19). b Schematic representation of the ITGα4β7-mediated transmigration of T lymphocytes (T cells) from blood vessels to the lamina propria of the jejunum, and details of the sampling area for subsequent analyses. c Dosage of α4β7pos CD45ROpos memory CD4 T cells in the lamina propria of the jejunum and of immune cells in the circulating blood of homozygous wild-type (0) and mutant (2) heifers (Additional file 1: Tables S20 and S21). ***: Student t-test p value ≤ 0.001. d Pictures of 247-day-old wild-type and 245-day-old homozygous mutant heifers, illustrating growth retardation in the latter, and analysis of average daily gain in 13 cases and 13 matched control heifers aged 6 months to 2 years (Additional file 1: Table S22). e Origin of H5P25 haplotype and ITGB7 mutation (see Additional file 1: Table S23 for details). f Proportion of animals that died, were slaughtered, or are still alive at 2 years of age for each combination of ITGB7 variant genotype and H5P25 status. Different symbols indicate significant differences (Fisher p value ≤ 0.01) between genotype-haplotype combinations in the proportions of animals within each of the three categories (Additional file 1: Table S24). g Analysis of age at first AI for the three genotypes at the ITGB7 variant (Additional file 1: Table S25). ***: Student t-test p value ≤ 0.001. h Effects of heterozygosity and homozygosity at the ITGB7 variant on 14 recorded traits (Additional file 1: Table S26). Only significant effects are shown (Benjamini–Hochberg adjusted Student’s t-test p value ≤ 0.01). GSD: genetic standard deviation. i Trimester repartition of the proportion of females that died or were slaughtered before reaching 6 years of age by genotype group at the ITGB7 substitution (Additional file 1: Table S27)