Categories: Muscle phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 604976 (gene) , 619030 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2000

Species-specific name: "Hampshire effect"

Species-specific symbol: RN

Species-specific description: The Rendement Napole (RN) gene was first documented by Leroy et al. (1990). In longissimus dorsi muscles, carriers of this dominant gene show lower pH, higher surface and internal reflectance values, lower protein extractability, lower water-holding capacity, lower Napole yield (yield after curing and cooking), and greater cooking loss. On the positive side, carriers have a lower shear force value, a stronger taste and smell, and greater acidity. The primary cause of these differences is that the mutant allele results in higher stored glycogen content in muscle.

Mapping: Using a genome scan with 63 markers, Milan et al. (1995) mapped the RN locus to chromosome SSC15, 18cM from marker S008. Fine-mapping on SSC15 by Milan et al. (1996) narrowed the location to "between markers Sw120 and Sw936, at 2 cM from Sw936 (LOD = 38.1)". These same authors also physically mapped Sw936, and hence RN, to SSC15q21-22. In an independent study involving a genome scan with 19 microsatellites and one other marker, Mariani et al. (1996) also mapped the RN locus to SSC15, and then fine-mapped it with a further three microsatellite markers. The closest marker, Sw936, is 4.8cM from RN. Noting that the next-nearest marker (S0088; 10.6 cM from RN) is 3cM from the DPP4 gene, which had been physically mapped to SSC15q2.1, Mariani et al. (1996) concluded that RN is located in the region SSC15q2.1-15qtel.

Molecular basis: Building on the mapping results describe above in the Mapping section, Milan et al. (2000) constructed a 2.5 Mb contig of BAC clones covering the region in which RN resides, and used it to fine-map the RN locus. Sequencing of the most likely BAC clone revealed three putative coding sequences, one which showed some homology with genes encoding the gamma subunit of AMP-activated protein kinase (AMPK). Noting that AMPK "has a key role in regulating energy metabolism in eukaryotic cells", Milan et al. (2000) had identified a likely positional coding sequence. Noting this coding sequence's similarity with, but distinctness from, the only two human genes then known to encode the gamma subunit of AMPK, namely PRKAG1 and PRKAG2, Milan et al. (2000) named their new gene PRKAG3. Sequencing of this gene in the RN genotypes revealed the causative mutation to be a missense mutation (c.599G>A) resulting in a "nonconservative substitution (R200Q)". The following year, Ciobanu et al. (2001) showed that one of the other alleles at this locus, namely I199V (first reported by Milan et al., 2000) has a substantial effect on glycogen content and meat quality in populations for which the R200Q allele is not segregating.

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

Breed: Hampshire Down (Sheep) (VBO_0001431).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: