A joint analysis using exome and transcriptome data identifies candidate polymorphisms and genes involved with umbilical hernia in pigs

Abstract

Background Umbilical Hernia (UH) is characterized by the passage of part of the intestine through the umbilical canal forming the herniary sac. There are several potential causes that can lead to the umbilical hernia such as bacterial infections, management conditions and genetic factors. Since the genetic components involved with UH are poorly understood, this study aimed to identify polymorphisms and genes associated with the manifestation of umbilical hernia in pigs using exome and transcriptome sequencing in a case and control design. Results In the exome sequencing, 119 variants located in 58 genes were identified differing between normal and UH-affected pigs, and in the umbilical ring transcriptome, 46 variants were identified, located in 27 genes. Comparing the two methodologies, we obtained 34 concordant variants between the exome and transcriptome analyses, which were located in 17 genes, distributed in 64 biological processes (BP). Among the BP involved with UH it is possible to highlight cell adhesion, cell junction regulation, embryonic morphogenesis, ion transport, muscle contraction, within others. Conclusions We have generated the first exome sequencing related to normal and umbilical hernia-affected pigs, which allowed us to identify several variants possibly involved with this disorder. Many of those variants present in the DNA were confirmed with the RNA-Seq results. The combination of both exome and transcriptome sequencing approaches allowed us to better understand the complex molecular mechanisms underlying UH in pigs and possibly in other mammals, including humans. Some variants found in genes and other regulatory regions are highlighted as strong candidates to the development of UH in pigs and should be further investigated.

A confirmed association between DNA variants in CAPN9, OSM, and ITGAM candidate genes and the risk of umbilical hernia in pigs

“…Of these, ACAN , MMPs , COLs , EPYC , VIT , CCBE1 , and LGALS3 have been indicated as candidates that deserve further investigation (Souza et al, 2020). The same research group later indicated DNA polymorphisms within new candidates (e.g., in genes responsible for myosin formation, muscle contraction, and skeletal muscle development) in the sequenced transcriptomes, which were potentially associated with UH in Landrace pigs (Savoldi et al, 2021). That analysis was performed on a very small group of UH vs. control animals, and the predicted effects of these variants for the encoded proteins was determined only by an in silico SIFT (sorting intolerant from tolerant) analysis.…”

“…That analysis was performed on a very small group of UH vs. control animals, and the predicted effects of these variants for the encoded proteins was determined only by an in silico SIFT (sorting intolerant from tolerant) analysis. These results thus need to be validated in a larger group of affected and control pigs (Savoldi et al, 2021). Altered muscle and connective tissue development in the umbilical ring seems to be a crucial cause of hernias.…”

“…In a recent study of hernias in the Landrace breed, performed using RNA sequencing, a candidate SNP was described in the integrin α M (ITGAM) gene, which is involved in ectodermal cell differentiation (Rodrigues et al, 2021). This variant was also indicated by the same research group (Savoldi et al, 2021) using the exomic data. There has also been report on the association between copy number variant (CNV) and UH.…”

Whole-Exome Sequencing Indicated New Candidate Genes Associated with Unilateral Cryptorchidism in Pigs

“…However, these studies were not sufficient to eliminate this defect from swine herds through animal selection [Sevillano et al, 2015]. This could be due to the limited power of the approaches used to identify the mutations involved with the differences in the genetic background of the swine populations used [Zanella et al, 2016;Lago et al, 2018;Joaquim et al, 2019], or by the environmental role in controlling this phenotype, as observed in umbilical hernias [Savoldi et al, 2021]. For example, Sevillano et al [2015] and Thaller et al [1996] highlighted the influence of maternal, intrauterine, and postnatal environments on the occurrence of cryptorchidism in pigs.…”