Categories: Muscle phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 136440 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2007

Species-specific name: Haplotype BHM

Species-specific symbol: BHM

Mapping: Medugorac et al. (2003) reported "the localization of the gene causing bovSMA within a genomic interval between the microsatellite marker URB031 and the telomeric end of bovine Chromosome (Chr) 24 (BTA24)" Krebs et al. (2006) refined the mapping "to an interval of approximately 0.8 cM at the very distal end of BTA24". Krebs et al. (2007) narrowed the location to a region containing three comparative positional candidate genes. In the course of their large-scale study of BovineSNP50 BeadChip haplotypes that are common but never homozygous, VanRaden et al. (2011) confirmed the mapping of this disorder to BTA24 at 58-63Mb (UMD 3.0 genome assembly).

Molecular basis: By examining three comparative positional candidate genes from their mapping results (see Mapping section), Krebs et al. (2007) reported strong evidence that this disorder in cattle is due to a mutation in "FVT1, encoding 3-ketodihydrosphingosine reductase, which catalyzes a crucial step in the glycosphingolipid metabolism". Specifically, the mutation is "a G-to-A missense mutation that changes Ala-175 to Thr". Interestingly, the FVT1 gene, officially known as KDSR, is not included in the list of genes in which mutations result in SMA in humans. In their table of reduced-fertility haplotypes, Cole et al. (2014) list this KDSR mutation as being the causal mutation for haplotype BHM, which is located at 62,118,139– 62,156,760bp on chromosome BTA24.

Breeds: Brown Swiss (Cattle) (VBO_0000166), Red Dane (Cattle) (VBO_0000353).
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: