Identification of Anal Atresia Susceptible Genes in Pig Model Based on Sequencing

Anal atresia (AA) is a common disorder in the development of the distal hindgut in pigs with a natural incidence from 0.1 % to 1.0%. Usually, the affected piglets will die or be discarded after birth. In this study, a total of 45 DNA samples including 27 affected indivadulas and 17 unaffected full sibs or parents were used for scanning the susceptible loci (genes) by using RAD sequencing with an average depth 5.14× covering 7.24% of the whole genome. Totally, 247,715 SNPs with MAF>0.05 were identified which spanning 18 autosomes and X chromosome. Whole genome association analysis with the case/control model revealed 11 SNPs with P value <0.05. Interestingly, the most significant SNP was located in the intron of LRP5 (low density lipoprotein receptor-related protein 5) gene on SSC2. By comparing the allele frequency between these case and control groups with chi square test, we found 12 SNPs showed p value <0.001, and the three SNPs with the lowest p values were located in the DKK3 (dickkopf WNT signaling pathway inhibitor 3) and FZD6 (frizzled class receptor 6) genes. It is worth mentioning that the three genes LRP5, DKK3 and FZD6 are all invovled in the Wnt signalling pathways. LRP5 protein acts as a co-receptor with Frizzled protein family members for transducing signals by Wnt proteins and DKK3 protein is the Wnt signaling pathway inhibitor. Our results showed the Wnt signalling genes may be associated with the pig’s anal atresia disease.