Fig. 5

A de novo missense mutation of FGFR2 is perfectly associated with dominant facial dysplasia syndrome (FDS) in a family of Holstein cattle. a . Non-parametric multipoint linkage analysis for FDS. A total of three significantly linked genome regions are shown in blue. b . Pedigree drawing and FGFR2 SNP genotypes. Filled black symbols represent affected calves with FDS, open symbols represent unaffected parents, squares indicate males and circles indicate females. The case-parent trio subjected to whole genome re-sequencing is indicated by IGV screenshots showing the presence of the chromosome 26 g.41'861'956C>A de novo variant. Note that the electropherograms presented below the pedigree symbols show that the mutant A allele is present in heterozygous form in FDS affected offspring only. c . Domain structure of the 840 amino acid FGFR2 protein. The missense variant is positioned in the exon 6 of the FGFR2 gene. The p.Trp309Cys change affects the third extracellular immunoglobulin-like domain (light blue) in front of a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain (dark blue). The bovine FGFR2 309 tryptophan residue that is substituted by a cysteine residue shows a high degree of conservation across the vertebrate kingdom.