Categories: Pigmentation phene

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: no

Key variant known: yes

Year key variant first reported: 2023

Species-specific name: Inhibitor of gold

Species-specific symbol: IG

Species-specific description: Bi et al. (2023): "The Inhibitor of gold (IG) or Cream phenotype was first described by Taylor [1932] and later analysed by Punnett [1948]. The autosomal recessive IG allele mainly dilutes the red/pheomelanic components of the plumage with minor effects on black/eumelanic components .... A general dilution of pigmentation is present in homozygous IG/IG birds that are also homozygous for the recessive wheaten allele (Y) at the MC1R locus and therefore exhibit only red pheomelanin pigmentation ... . The phenotype is apparent already at hatch. In contrast, IG birds carrying other MC1R alleles that allow expression of both eumelanin and pheomelanin show a dilution of red pheomelanic pigmentation but no visible dilution of black eumelanic pigmentation ... . Male IG chickens display a greater dilution of pheomelanin pigmentation than IG females, suggesting the involvement of sex-specific factors."

Inheritance: Bi et al. (2023): "A three-generation intercross was set up between three Rhode Island Red (RIR) birds carrying the wild-type allele at the IG locus (N) and four individuals from an experimental population fixed for the Inhibitor of Gold allele to produce a pedigree for mapping the IG locus. A total of 413 F2 chickens were born, of which 83 (20.1%) displayed the dilution of pheomelanin pigmentation caused by IG homozygosity. This represents a minor but significant deviation from the 25% expected based on Mendelian segregation (χ2 = 5.30, df = 1, P = 0.02)."

Mapping: Bi et al. (2023): "linkage analysis was performed using 159 F2 individuals from a three-generation intercross segregating at the IG-locus." The IG locus was mapped "to a 3.71 Mb region on chicken chromosome 6 defined by the closest flanking markers IG1250Kb and AP3UP500Kb ...." Identical-by-descent mapping refined the region to a 261,682 bp IBD region containing the COMTD1, and two lncRNAs.

Molecular basis: Whole genome sequencing of an IG/IG homozygote identified a 2-bp insertion in exon 5 of COMTD1 as likely causal variant (Bi et al., 2023). This variant was validated by analysis of publicly available chicken whole genome sequencing data and by genotyping "a large pedigree of an intercross between a White Leghorn line (Obese Line) and red junglefowl, which segregated at the IG and sex-linked Silver loci ... [as well as] genotyping " (i) IG birds from five different populations and (ii) wild-type birds representing 7 domestic breeds and three junglefowl species all displaying red plumage phenotypes. ... Two different COMTD1 transcripts were detected in IG birds: a full-length transcript (IG1), which is out of frame after the 2 bp insertion in exon 5 leading to a premature stop codon, and an alternative splice form (IG2), which carries four out-of-frame codons from exon 5, lacks exon 6, but contains exon 7 in frame."

Associated gene: