In other species: rock pigeon , turkey , dog , domestic cat , horse , pig , Arabian camel , guanaco , llama , Western roe deer , taurine cattle , goat , sheep , domestic guinea pig , alpaca , springbok

Categories: Skeleton phene (incl. short stature & teeth) , Limbs / fins / digit / tail phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 174500 (trait) , 605522 (gene) , 188740 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2010

Cross-species summary: Often called preaxial polydactyly (PPD)

Species-specific symbol: Po

History: This is one of the first five animal traits (all in chickens) to be described as Mendelian, by Bateson and Saunders (1902; pages 87-124). The other four traits are Rose-comb (OMIA 000884-9031), Pea-comb (OMIA 000782-9031), Dominant White (OMIA 000373-9031), and Yellow skin (OMIA 001449-9031).

Mapping: This disorder was originally mapped to linkage group E (Warren, 1949). Using bulked segregant analysis with microsatellite markers, Pitel et al. (2000) mapped it to chromosome GGA2p, a result confirmed by Yang et al. (2013). Dorshorst et al. (2010) refined the location to 4.8Mb on chromosome GGA2p. Using linkage analysis and GWAS in 367 members of an F2 of a cross between Beijing-You chickens and Cobb-Vantress commercial broilers, each genotyped with the Illumina 60K Chicken SNP Beadchip (yielding 42,585 informative SNPs), Sun et al. (2014) confirmed the SSH region on chromosome GGA2 as being the most important, but also obtained genome-wide significance for SNPs on chromosomes GGA20 and GGA26. Sheng et al. (2015) reported the strongest association with Polydactyly in a region on chromosome GGA2 that contains the BRAM1 gene. This paper was withdrawn in March 2016 (Sheng et al., 2016). Zhang et al. (2016) showed that the causal mutation for Polydactyly in European breeds maps to the same region of chromosome GGA2 as the mutation that is causal in Chinese breeds, but is not the same mutation.

Molecular basis: Polydactyly results from faults in the regulation of the developmental gene Sonic Hedgehog (SHH), which is expressed only at the border of the posterior limb bud, in a region called the zone of polarizing activity (ZPA). The faults in regulation result from mutations in an enhancer located in intron 5 of the LMBR1 gene, located about 1 MB upstream of SHH. The enhancer is called the ZPA regulatory sequence (ZRS). Thus polydactyly results from mutations in ZRS, which affect expression of SHH in the developing limb bud. The first report of the causal mutation (a SNP in the SHH enhancer) was by Dorshorst et al. (2010). This discovery was confirmed by Maas et al. (2011). Zhang et al. (2016) showed that this mutation is causal in 24 indigenous Chinese breeds, but is not causal for Polydactyly in the Houdan breed, from France. He et al. (2017): "a highly purebred BF [Beijing fatty] line with 100% penetrance of Po was obtained and served as an ideal model for the study of Po in fowls. By observing the process of pure breeding and cross breeding, we provided evidence that chicken polydactyly was a complete dominant trait [in this line]. With the help of an integrated strategy of RAD-seq [restriction-site-associated DNA sequencing] and resequencing, we further confirmed that this dominant trait was highly associated with the genotype of rs80659072 [(Gallus_gallus-5.0) GGA2:8500245C>T (in an intron of LMBR1)] in the BF line." Chu et al. (2017): "The plausible mutation rs80659072 in the zone of polarizing activity regulatory sequence (ZRS) in chickens was an essential but not sufficient condition for polydactyly and polyphalangy in Beijing You chickens."

Clinical features: "Homozygous (Po/Po) and heterozygous (Po/+) mutants may have an additional preaxial digit on one or both feet and/or wings; or affected individuals may display a longer than normal first digit on one or both feet" (Robb et al., 2011)

Breeds: Beijing You, China (Chicken) (VBO_0006660), Silkie (Chicken) (VBO_0000619).
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: