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

Categories: Limbs / fins / digit / tail phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 174500 (trait) , 605522 (gene) , 188740 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Recessive

Considered a defect: yes

Key variant known: no

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

Inheritance: Gorbach et al. (2010) provided convincing data that this disorder is inherited but could find no evidence of a single gene of large effect. A whole-genome scan with a SNP chip identified a 25 Mb region on chromosome SSC5 that appears to play some role in the development of this disorder. Nikitin et al. (2021) report polydactyly in mini-pigs with a likely recessive mode of inheritance.

Mapping: Ma et al. (2020) sequenced "two PPD [preaxial polydactyly][Large White] families consisting of four affected and 20 normal individuals ... A strong association was identified at ABCC4 and it encodes a transmembrane protein involved in ciliogenesis. We found that the affected and normal individuals were highly differentiated at ABCC4, and all the PPD individuals shared long haplotype stretches as compared with the unaffected individuals. A highly differentiated missense mutation (I85T) in ABCC4 was observed at a residue from a transmembrane domain highly conserved among a variety of organisms."
Hao et al. (2024) "analyzed a group of Large White pigs with postaxial polydactyly, including 29 cases and 79 controls from 24 families. High-depth sequencing was performed on 20 pigs, while low-depth sequencing was improved through imputation for the remaining pigs. A genome-wide association study (GWAS) and genetic differentiation were conducted using the resequencing dataset, resulting in the identification of 48 significantly associated SNPs and 27 candidate regions. The genetic differentiation regions on chromosomes 5 and 18, which harbored GWAS-identified SNPs, were delineated as confidence regions. The confidence region at Chr18: 1.850-1.925 Mb covers the fifth intron of LMBR1, a gene that contains an important regulatory element for SHH, known as ZRS." 

Molecular basis: Ma et al. (2020) sequenced "two PPD [preaxial polydactyly][Large White] families consisting of four affected and 20 normal individuals ... A strong association was identified at ABCC4 and it encodes a transmembrane protein involved in ciliogenesis. We found that the affected and normal individuals were highly differentiated at ABCC4, and all the PPD individuals shared long haplotype stretches as compared with the unaffected individuals. A highly differentiated missense mutation (I85T) in ABCC4 was observed at a residue from a transmembrane domain highly conserved among a variety of organisms."

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

Breed: Large White (Pig) (VBO_0001163).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below