Whole genome resequencing reveals an association of ABCC4 variants with preaxial polydactyly in pigs

Abstract

Background: Polydactyly is one of the most common congenital limb dysplasia in many animal species. Although preaxial polydactyly (PPD) has been comprehensively studied in humans as a common abnormality, the genetic variations in other animal species have not been fully understood. Herein, we focused on the pig, as an even-toed ungulate mammal model with its unique advantages in medical and genetic researches, two PPD families consisting of four affected and 20 normal individuals were sequenced. Results: Our results showed that the PPD in the sampled pigs were not related to previously reported variants. 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. Conclusions: This study reports ABCC4 as a new candidate gene and identifies a missense mutation for PPD in pigs. Our results illustrate a putative role of ciliogenesis process in PPD, coinciding with an earlier observation of ciliogenesis abnormality resulting in pseudo-thumb development in pandas. These results expand our knowledge on the genetic variations underlying PPD in animals.

Whole genome resequencing reveals candidate genes for postaxial polydactyly in Large White pigs

“…The confidence regions and candidate gene proposed in our study differ from the results of Ma et al. 's study but are consistent with findings from studies in humans and other vertebrate species (Ma et al., 2020). These results not only suggest that the potential pathogenic mechanisms for preaxial and postaxial polydactyly in Large White pigs are distinct but also imply that the role of ZRS in LMBR1 for toe development is conserved across Large White pigs, humans and other animals.…”

“…Referring to previous reports, we confirmed that the imputation accuracy exceeded 91.57% when using 80K chip data (Fuller et al., 2020). We examined the genotype of the previously reported missense mutation on ABCC4 in the high‐depth resequencing dataset using the igv software (Ma et al., 2020; Robinson et al., 2017). We found that the missense mutation was fixed as AA in our dataset, indicating that it is unlikely to be an associated locus in our study.…”

“…Previous studies have shown that genes including GLI1, GLI3, IQCE, KIAA0825, EP300, VPS25 and BBS10 are associated with polydactyly (Ahmad et al, 2023;Alvarez-Satta et al, 2017;Handschuh et al, 2014;Ni et al, 2019;Sheth et al, 2012). It is noteworthy that Ma et al's (2020) study identified a significant association between preaxial polydactyly and a missense mutation in ABCC4 in pigs, which is currently the only genomic study to investigate porcine polydactyly.…”

“…It is noteworthy that Ma et al. 's (2020) study identified a significant association between preaxial polydactyly and a missense mutation in ABCC4 in pigs, which is currently the only genomic study to investigate porcine polydactyly.…”

“…Polydactyly is a rare anomaly in pigs that demonstrates high genetic heterogeneity across different populations (Ma et al., 2020). The extra toes of affected pigs do not serve any biological function and can cause hoof tears and infections, thereby negatively impacting pig welfare and profitability of the pig industry (Nikitin et al., 2021).…”