Posterior means and 95% posterior credibility intervals (PCI) of sensitivities (Se) and specificities (Sp) for the PCR tests performed in bulk tank milk (PCR BTM) and indoor dust samples (PCR DUST), for the 2 models with different priors for the specificity of PCR DUST.

<p>PCR BTM (n = 380) and PCR DUST (n = 380) tests were performed in 95 dairy cattle herds in the Finistère department, France between November 2012 and April 2014.</p

Binary and quantitative test responses for the PCR tests performed in bulk tank milk (PCR BTM) and indoor dust samples (PCR DUST) according to the stratified population.

<p>PCR BTM (n = 380) and PCR DUST (n = 380) tests were performed in 95 dairy cattle herds in the Finistère department, France between November 2012 and April 2014.</p

Posterior means and 95% posterior credibility intervals (PCI) of sensitivities (Se) and specificities (Sp) of the tests combined in parallel or serial reading (2 PCR tests performed in bulk tank milk, PCR BTM, and indoor dust samples, PCR DUST) for the 2 models with different priors for the specificity of PCR DUST.

<p>PCR BTM (n = 380) and PCR DUST (n = 380) tests were performed in 95 dairy cattle herds in the Finistère department, France between November 2012 and April 2014.</p

The participating cells in lesions.

<p>(A) Prominent astrocytic reaction as evidenced by anti-GFAP antibody (GFAP, green; Dapi, blue). Astrocytic reaction, engulfing the lesion; a few astrocytic feet penetrated the lesion (<i>white asterisk</i>). (B) Microglial activation, immunolabelled by anti Iba1, reproduced similar topography as the astrocytic reaction by surrounding the lesion, and few microglial cell processes infiltrated the lesion (<i>white asterisk</i>) (Iba1, green; Dapi, blue). Concurrently, astrocytic and microglial cell activations are present not only around the lesions but also elsewhere. (C) Immunostaining of anti-oligodendrocyte specific protein (anti-OSP), a cell membrane oligodendrocyte marker (OSP, green; Dapi, blue. Big or confluent lesions (<i>white arrows</i>), where the centre is occupied by many OSP-positive and intricate processes of different shapes and sizes, which presumably depend on the plane section. (D) Double immunostaining showed that the two markers–cytoplasmic (MBP) (red) and membrane (OSP) (green)–of oligodendrocytes were present together in the demyelinating lesions and the centre of the plaque was double-immunostained (<i>white arrows</i>). (E) Anti-actin immunostaining (red), Dapi (blue), actin protein aggregates were also accumulated in the centre (<i>arrow</i>) of the plaque and in the cytoplasm of some surrounding cells (<i>white arrows</i>). (F) Double immunostaining of actin (red) and MBP (green) Dapi (blue). Within the core of the plaque with actin immunostaining, note the presence of oligodendrocyte processes (<i>white arrows</i>). Scale bar: (A) and (B) 30 μm, (C) 20 μm, (D) 50 μm, (E) and (F) 20 μm.</p

Genotyping of animals of 7 French breeds for the KIF1C mutation.

<p>Genotyping of animals of 7 French breeds for the KIF1C mutation.</p

Variants detected by whole-genome sequencing of 3 animals, including 2 with progressive ataxia.

<p>Variants detected by whole-genome sequencing of 3 animals, including 2 with progressive ataxia.</p

Association between the ataxia variant and morphology traits in animals of the Charolais breed.

<p>Association between the ataxia variant and morphology traits in animals of the Charolais breed.</p

Identification of a variant in <i>KIF1C</i> gene in bovine animals affected by progressive ataxia.

<p>(A) Sanger sequence electropherogram traces for the causal mutation in the bovine <i>KIF1C</i> gene done on a wild type (WT), a heterozygous carrier and an affected animal. The G>A substitution affects the last nucleotide of bovine exon 5. Translated amino acids are presented below the genomic sequence. (B) Schematic diagram of coding exons from <i>KIF1C</i> gene in cattle (protein with 1104 amino acids) with the predicted functional domains of the protein, with the position of the mutation indicated (<i>arrow</i>). (C) Based on protein alignment, the affected amino acid is highly conserved in vertebrates and located in a conserved region of the protein. MACMU, <i>Macaca mulatta</i>; FELCA, <i>Felis catus</i>; BOVIN, bovine (<i>Bos taurus</i>); CANLF, <i>Canis lupus familiaris</i>; XENTR, <i>Xenopus tropicalis</i>; DANRE, <i>Danio rerio</i>.</p

Quantification of the length of paranodal section in cerebellar peduncles of non-affected and affected cattle.

<p>(A) Caspr positivity was concentrated in two paranodal compartments on either side of the node of Ranvier. The immunostaining was observed on myelinated fibres of various diameters. (Caspr green, Dapi blue). (B) The lengths of the paranodal region vary slightly; however, in affected white matter this length appeared more variable and greater within and around the demyelinating lesion. (C) Quantitative comparison and graphic representation of these lengths in WT controls, within and outside the lesions. Numbers of quantified paranodal sections in WT controls: 570; in affected cattle: inside lesion 115 paranodes and outside lesion 194 paranodes. Scale bar: (A) and (B) 40 μm.</p

<i>KIF1C</i> variant affects mRNA expression and leads to a functional knock-out.

<p>(A) Schematic diagram of the <i>KIF1C</i> gene in bovine sequence, located on chromosome 19, with the mutation indicated by an arrow. Primer pairs p1 and p2 (respectively amplifying <i>KIF1C</i> exons 1 to 11 and exons 13 to 20) are shown downstream of the diagram. RT-PCR from WT and affected bovine brains with p1 and p2 primer pairs demonstrated that <i>KIF1C</i> expression is modified in affected animals both in quantity–with mRNA decay–and quality (several transcripts in affected animals). <i>RPL13</i> (ribosomal protein L13) was used as a housekeeping gene. (B) Schematic diagram of <i>KIF1C</i> transcripts in affected bovine. The normal transcript bears the G>A mutation and leads to a mutated protein; the alternative transcript results from defective splicing and leads to exon 5 skipping. (C) Proteins were extracted from brains of WT and affected bovines, and from HeLa cells. Samples were analysed by immunoblotting with antibody against KIF1C proteins. No KIF1C protein was found in affected animals. WT, wild type; Aff, affected.</p