In other species: pig

Categories: Nervous system phene

Possibly relevant human trait(s) and/or gene(s) (MIM number): 149400 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: no

Mode of inheritance: Multifactorial

Considered a defect: yes

Key variant known: no

Species-specific name: posterior paralysis; hind-limb paralysis

Inheritance: Leipold et al. (1967) concluded that the "pattern of occurrence suggested recessive inheritance" but had insufficient evidence for a firm conclusion. Hanset et al. (1993) fitted a single-locus model to more extensive data, but the model was not sufficient to explain all occurrences.

Mapping: From a GWAS of 46 Holstein AI bulls affected with bovine spastic paresis (BSP) and/or bovine spastic syndrome (BSS), and 213 unspecified control cattle, each genotyped with the BovineLD BeadChip, yielding 9,092 markers, Krull et al. (2020) identified four QTL on chromosome BTA15, and one each on BTA8 and BTA19.

Markers: Whole-genome sequencing of "one affected sire and his two full brothers (one known to be unaffected), two further affected sires and their respective parents, and the affected grandfather (mother's father) of one of these" enabled Krull et al. (2020) to identify a potential marker at BTA15:g.78135822_78135823insC (UMD3.1). However, even allowing for the relatively late onset of this disorder, the high frequency of this variant (73.7%) in 3,093 animals from the 1000 Bull Genomes Project suggests that more work is required before this variant is put to any use as a marker for BSS/BSP.

Molecular basis: In an imaginative approach to investigating an intractable disorder, Pariset et al. (2013) compared gene expression in the most likely candidate tissue (the spinal cord from C6 to L6) between affected and normal animals, using RNA from two pools (of 4 affecteds and 4 normals) on a 15k cDNA expression array that includes cDNA from a bovine brain library and a bovine monocyte library. The 268 differentially expressed genes suggested involvement of "a defective glycinergic synaptic transmission in the development of the disease and an alteration of calcium signalling proteins". Clusters of differentially expressed genes are located "in narrow regions on BTA3, BTA5, BTA18 BTA21 and BTA22". For the 86 genes that were under-expressed in affected animals, the only significant KEGG pathway was C2 (Neurodegenerative Diseases).

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Prevalence: Krull et al. (2020): "An allele frequency of the [g.78135822_78135823insC] variant of 0.74 was determined in 3,093 samples of the 1000 Bull Genomes Project."