In other species: dog

Categories: Nervous system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 612123 (gene) , 251950 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2016

Species-specific name: Weaver syndrome; Haplotype BHW; bovine degenerative progressive myeloencephalopathy

Species-specific symbol: BHW, BDPME

Mapping: In one of the very early genome scans, Georges et al. (1993) genotyped 33 affected Brown Swiss, plus (where possible) their sires, dams and normal siblings, with "82 multisite haplotypes . . . , 38 variable number of tandem repeat markers . . . , and 233 bovine dinucleotide microsatellites". The 78th microsatellite tested in two-point linkage analysis, namely TGLA116, showed a significant recombination fraction of 3% with the disorder. No other markers showed any linkage. Subsequent somatic-cell-hybrid mapping enabled TGLA116 to be allocated to bovine synteny group 13. In the course of their large-scale study of BovineSNP50 BeadChip haplotypes that are common but never homozygous, VanRaden et al. (2011) mapped this disorder to BTA4 at 45-56Mb (UMD 3.0 genome assembly). By conducting a GWAS on 20 carriers and 51 normal Brown Swiss, each genotyped with the Illumina BovineHD assay (yielding 733,937 informative SNPs), and subsequent fine-mapping, McClure et al. (2013) refined the mapping of this disorder to a 252 kb haplotype on chromosome BTA4, which will provide greater accuracy for carrier detection. In their table of reduced-fertility haplotypes, Cole et al. (2014) list the "Weaver" haplotype as haplotype BHW (for Brown Swiss/Haplotype/Weaver).

Molecular basis: Kunz et al. (2016) reported a likely causal mutation as "a missense mutation (p.S568N, c.G1703A; [Chr4: 49,878,773 bp, rs800397662]) in the PNPLA8 gene that encodes patatin-like phospholipase domain containing 8".

Prevalence: As reported by Kunz et al. (2016), "Genotyping for the candidate causal mutation in a random sample of 2334 current Braunvieh animals suggested a frequency of the Weaver allele of 0.26 %"

Genetic testing: Using the powerful tool of imputation from 50K SNP genotypes, McClure et al. (2013) reported that <7,500 Brown Swiss have now been characterised as carriers or non-carriers of the haplotype described in the Mapping section (above). Identification of a likely causal mutation by Kunz et al. (2016) (see Molecular basis section) has the potential to replace the haplotype test with a specific SNP test.

Breed: Brown Swiss (Cattle) (VBO_0000166).
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).

Associated gene: