In other species: ducks , Japanese quail

Categories: Pigmentation phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 605495 (gene) , 237450 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2013

Species-specific name: Oocyan

Species-specific symbol: O

History: This trait was first described as occurring in American Araucana chickens by Punnett (1933).

Inheritance: Punnett (1933) reported autosomal dominant inheritance for this trait.

Mapping: Wang et al. (2010) mapped this trait to a region from 67.3–69.1 Mb on chromosome GGA1 in the Dongxiang chicken breed. Wragg et al. (2012) refined the location in the native Chilean Mapuche fowl (the original source of the Araucana breed of North America and Europe) and in derivative European breeds to "two small regions (Gga 1:67.25–67.28 Mb, Gga 1:67.28–67.32 Mb) totalling ~75 Kb". Using linkage analysis in the candidate region on data from 146 F2 hens from a cross between homozygous blue and homozygous non-blue birds of the Dongxiang breed, Wang et al. (2013) refined the location to "a ~120 kb region from 67296991 bp to 67416784 bp on chromosome 1 on the UCSC chicken genome (May 2006 assembly)".

Molecular basis: The refined location determined by Wang et al. (2013) contains four positional candidate genes. Only one of these, SLCO1B3, is expressed in the shell gland of the uterus of blue-shelled hens but not in non-blue-shelled hens. Sequencing revealed the causal mutation to be "a ~4.2 kb [retroviral] EAV-HP insertion in the 5′ flanking region of SLCO1B3" (Wang et al., 2013). A genotyping survey of 38 chickens from two other breeds in which blue-eggshell segregates (Lushi and Araucana, the latter from North America) showed complete correlation of the presence/absence of the insertion mutation with blue-eggshell genotype. Eight other breeds in which blue eggshells do not appear were homozygous for the absence of the insertion mutation. Interestingly, the site of the insertion in the Araucana breed is 23bp upstream of the (identical) insertion site for the two Chinese breeds (Dongxiang and Lushi), indicating that the Chinese and American mutations arose independently (Wang et al., 2013). Later in the same year, Wragg et al. (2013) reported the same insertion mutation in native chickens of Chile (Mapuche fowl) and in European derivative breeds. Consistent with the Araucana breed having arisen from the Chilean Mapuche fowl, the insertion in these chickens is at the same location as reported by Wang et al. (2013) for the Araucana breed. Wragg et al. (2013) also confirmed the different site of insertion in Chinese breeds, thus confirming the independent occurrence of the insertion in native Chinese and native Chilean chickens. As noted by Wragg et al. (2013), the fact that all European breeds with blue eggshells have the Mapuche insertion site rather than the Chinese insertion site suggests "that the presence of blue eggs in Mapuche fowl, modern European and American breeds, did not involve birds from Asia". As also noted by Wragg et al. (2013), the fact that the insertion is not present in any of the jungle fowl species from which domestic chickens arose, and the near-identity of sequence of the Chinese and Chilean insertions, suggest that the insertions are recent, post-domestication events. Li et al. (2019) showed that "methylation of the promoter region of SLCO1B3 was significantly negatively correlated with both SLCO1B3 expression in the shell gland tissue and eggshell color. In addition, we predicted that CpG5 and CpG8 may be key sites for regulating SLCO1B3 gene transcription. Our findings show that as the level of methylation increases, methylation of the CpG5 and CpG8 sites hinders the binding of transcription factors to the promoter, reducing SLCO1B3 expression during the late period and resulting in a lighter eggshell color." Chen et al. (2020) "observed an alteration in the expression patterns of SLCO1B3 ... due to the retroviral EAV-HP insertion in different genotypes and sexes of blue-eggshell Yimeng chickens." Chen and Wang (2022): "did not detect the EAV-HP in BGC [blue-greenish coloration] samples of [Lueyang black-boned chicken] LBC, but found a strong positive correlation between SLCO1B3 expression levels in shell glands and eggshell biliverdin concentration." The authors propose "a new molecular mechanism that single nucleotide variants at the promoter region of SLCO1B3 can alter gene expression and result in chicken BGC." Altgilbers et al. (2022) "demonstrated that after testing multiple gRNAs, one CRISPR/Cas9 guide pairing successfully eliminated the entire provirus (EAV-HP) on chromosome 1 in male chicken cell lines carrying the blue allele." This study involves genetically modified organisms (GMO).

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

Breeds: Araucana (Chicken) (VBO_0000445), Crèvecoeur (Chicken) (VBO_0000517), Dong, an chicken, China (Chicken) (VBO_0006672), Gallina Mapuche, Argentina (Chicken) (VBO_0006532), Legbar (Chicken) (VBO_0000559), Lueyang, China (Chicken) (VBO_0006723), Lushi, China (Chicken) (VBO_0006725), Yimeng Blue, China (Chicken) (VBO_0016867).
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: