A survey of copy number variation in the porcine genome detected from whole-genome sequence

Authors: Keel, Brittney; Nonneman, Danny - Dan; Lindholm-Perry, Amanda; Oliver, William; Rohrer, Gary

Submitted to: Frontiers in Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/12/2019
Publication Date: 8/16/2019
Citation: Keel, B.N., Nonneman, D.J., Lindholm-Perry, A.K., Oliver, W.T., Rohrer, G.A. 2019. A survey of copy number variation in the porcine genome detected from whole-genome sequence. Frontiers in Genetics. 10:737. https://doi.org/10.3389/fgene.2019.00737.
DOI: https://doi.org/10.3389/fgene.2019.00737

Interpretive Summary: One of the important challenges in post-genomic biology is relating observed phenotypic variation to the underlying genotypic variation. Genome-wide association studies have made thousands of connections between single nucleotide polymorphisms and phenotypes, but this type of variation only represents a small percentage of the total heritable variation. Hence, determining other types of DNA variation that may make a substantial contribution to variability in complex traits is a meaningful goal. Copy number variations (CNV) are gains and losses of large regions of genomic sequence between individuals of a species. It is hypothesized that CNV represent a significant source of genetic variation, as they have been shown to cover approximately 7% of the mouse genome, 12% of the human genome, and 7% of the cattle genome. ARS scientists have sequenced the genome of 240 members of a heavily phenotyped experimental herd of swine and identified 3,538 CNV covering approximately 1% of the swine genome. A larger than expected number of genes overlapped by CNV were found to be involved in organism development. Additionally, CNV were shown to overlap several known regions of DNA that correlate with variation in economically relevant swine phenotypes. The focus of future work will be to discover the extent to which CNV affect economic traits of interest and how to incorporate them into genomic selection systems.

Technical Abstract: Copy number variations (CNV) are gains and losses of large regions of genomic sequence between individuals of a species. Although CNV have been associated with various phenotypic traits in humans and other species, the extent to which CNVs impact phenotypic variation remains unclear. In swine, as well as many other species, relatively little is understood about the frequency of CNV in the genome, sizes and locations, and other chromosomal properties. In this work, we identified and characterized CNV by utilizing whole-genome sequence from 240 members of an intensely phenotyped experimental swine herd at the U.S. Meat Animal Research Center (USMARC). These animals included all 24 of the purebred founding boars (12 Duroc and 12 Landrace), 48 of the founding Yorkshire-Landrace composite sows, 109 composite animals from generations 4 through 9, 29 composite animals from generation 15, and 30 purebred industry boars (15 Landrace and 15 Yorkshire) used as sires in generations 10 through 15. Using a combination of split reads, paired-end mapping, and read depth approaches, we identified a total of 3,538 copy number variable regions (CNVRs), including 1,820 novel CNVRs not reported in previous studies. The CNVRs covered 0.94% of the porcine genome and overlapped 1,401 genes. Gene ontology analysis identified that CNV-overlapping genes were enriched for functions related to organism development. Additionally, CNVRs overlapped with many known quantitative trait loci (QTL). In particular, analysis of QTL previously identified in the USMARC herd showed that CNVRs were most overlapped with reproductive traits, such as age of puberty and ovulation rate, and CNVRs were significantly enriched for reproductive QTL.