A Genome-wide Copy Number Variation Association Study Identifies Susceptibility Genes For Pig Hernia

Copy number variations（CNVs）are genomic structural variants, which includingdeletions, insertions, duplications and complex multi-site of DNA segments ranging fromone kilobase to several megabases. It covers a large scale of the whole genome withdifferent forms. As genetic marker, CNV is inheritable, relatively stable and with highlyheterogeneous. Therefore, it is considered as an important source of ge netic variations andphenotypic diversity for organisms. It also plays an important role in the formation ofcomplex traits or diseases by disrupting gene expression and altering gene dosage.Pig hernia, such as umbilical hernia（UH）and scrotal/inguinal hernia（S/IH）, is oneof the most common growth and developmental defects in pigs, leading to considerableeconomic loss and serious animal welfare problem. As a complex disease which influencedby both genetic and environmental factors, coupled with the limitation of research methodsand techniques, the genetic dissection of swine hernia has developed very slowly.To investigate whether copy number variations（CNVs）contribute to pig hernia, weperformed a case-control genome-wide CNV association study using the Porcine SNP60SNP data and PennCNV algorithm in1303pigs from Duroc, Landrace, Large White andPietrain breeds. We constructed a genomic map containing6193CNVs pertaining to737CNV regions（CNVRs）from905QC qualified individuals, and found20CNVs associatedwith the risk for umbilical hernia or inguinal/scrotal hernia through genome-wide CNVassociation analysis, respectively. To confirm the authenticity of CNV detected byPennCNV, ten most significantly associated CNVs chosen from the40CNVs werevalidated using quantitative real-time PCR（qPCR), five of which were confirmed with avalidation rate of50%. Notably, a rare CNV（14:13030843-13059455）most associatedwith umbilical hernia with a permutation corrected p value of0.0015（pertaining to CNVR569）occurred exclusively in7Duroc affected individuals and SNPs surrounding the CNVdid not show association signals, indicating that rare CNV may be one of the pathogenesisfor the formation of pig umbilical hernia. The NUGGC gene partially encompassed byCNV （14:13030843-13059455） has been reported to be associated with humanomphalocele, and may be a promising candidate gene for umbilical hernia for furtherstudy.In summary, the genome-wide CNV association analysis for pig hernia provides anew insight into understanding the genetic basis of complex disease traits. This study haslaid a solid theoretical basis for future verification and fine mapping of susceptible genesfor pig hernia in a larger population, and offered scientific basis for deciphering thecomplex genetic mechanism of pig hernia.