In other species: sheep

Categories: Nervous system phene

Single-gene trait/disorder: no

Mode of inheritance: Multifactorial

Disease-related: yes

Key variant known: no

Species-specific name: also called inherited periodic spasticity, IPS

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.
Jacinto et al. (2024) investigated 7 affected unrelated Holstein cattle with a diagnosis of spastic syndrome due to "intermittent spasm of the skeletal muscles of the pelvic girdle". Whole genome sequencing analysis did not reveal any homozygous private variants common to all cases. "Searching for homozygous rare variants considering each case individually, allowed the identification of a rare recessive likely pathogenic missense variant in TOR3A ...  [and] seven potentially dominant de novo mutations or inherited alleles as private heterozygous ... variants of uncertain significance involving seven different NMD candidate genes: MPEG1, LHX8, WHAMM, NGRN, TTN, ATP1A1, PCDH1. All eight candidate causal variants identified were predicted to be deleterious."

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."

Breeds: Angus (Cattle) (VBO_0000104), Ayrshire (Cattle) (VBO_0000120), Brown Swiss (Cattle) (VBO_0000166), Dairy Shorthorn (Cattle) (VBO_0000186), Guernsey (Cattle) (VBO_0000227), Hereford (Cattle) (VBO_0000232), Holstein Friesian (Cattle) (VBO_0000239), Jersey (Cattle) (VBO_0000250), Simmental (Cattle) (VBO_0000380).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).