Research Article: Genome-wide association study between CNVs and milk production traits in Valle del Belice sheep

Date Published: April 23, 2019

Publisher: Public Library of Science

Author(s): Rosalia Di Gerlando, Anna Maria Sutera, Salvatore Mastrangelo, Marco Tolone, Baldassare Portolano, Gianluca Sottile, Alessandro Bagnato, Maria Giuseppina Strillacci, Maria Teresa Sardina, Roberta Davoli.


Copy number variation (CNV) is a major source of genomic structural variation. The aim of this study was to detect genomic CNV regions (CNVR) in Valle del Belice dairy sheep population and to identify those affecting milk production traits. The GO analysis identified possible candidate genes and pathways related to the selected traits. We identified CNVs in 416 individuals genotyped using the Illumina OvineSNP50 BeadChip array. The CNV association using a correlation-trend test model was examined with the Golden Helix SVS 8.7.0 tool. Significant CNVs were detected when their adjusted p-value was <0.01 after false discovery rate (FDR) correction. We identified 7,208 CNVs, which gave 365 CNVRs after aggregating overlapping CNVs. Thirty-one CNVRs were significantly associated with one or more traits included in the analysis. All CNVRs, except those on OAR19, overlapped with quantitative trait loci (QTL), even if they were not directly related to the traits of interest. A total of 222 genes were annotated within the significantly associated CNVRs, most of which played important roles in biological processes related to milk production and health-related traits. Identification of the genes in the CNVRs associated with the studied traits will provide the basis for further investigation of their role in the metabolic pathways related to milk production and health traits.

Partial Text

The availability of several forms of DNA variants, such as single nucleotide polymorphisms (SNPs) and copy number variants (CNVs), has played an important role in phenotypic variation studies. Most genetic and genome-wide association studies (GWAS) have investigated the associations between SNPs as genetic variants and complex and economically important traits, with the aim of identifying subsets of markers able to explain traits [1–5]. CNVs are polymorphic genomic regions, including deletions, duplications and insertions that involve DNA segment ranging from 1 kb to several Mb, that vary compared to a reference genome [6]. CNVs have been shown to be associated with complex traits in several species, including chimpanzees [7], rats [8], and mice [9], and in livestock species such as cattle [10–14], goats [15], and pigs [16, 17]. Like SNPs, these genomic structural variations are considered as important genetic markers of phenotypic variation for complex traits. CNVs have recently been used as markers of phenotypic variation, environmental adaptability, and for economically important traits or disease susceptibility in livestock species [18–20]. However, few studies on CNVs have been published for sheep. Some previous studies [21–23] analyzed CNVs based on comparative genome hybridization arrays, while others [24–27] detected CNVs using SNP microarrays. GWAS using CNVs and phenotypes have been developed in cattle breeds [19, 20, 28–31] and in swine [32, 33]. However, to the best of our knowledge, no GWAS between CNVs detected using the OvineSNP50K BeadChip array and economically important traits (milk, meat, etc) in sheep breeds have been published.

This study investigated a GWAS between CNVs and milk-production traits in sheep. Although this is the first time that a similar study was performed on sheep, several genomic regions including CNVs affecting these traits have been identified. However, considering the relative low number of individuals affecting the power of the association analysis, our results constitute a preliminary report on the association between these markers and quantitative traits in sheep. Therefore, further analysi on a wider sample could provide more robust results and could be of value for future studies.

At present, limited knowledge is available on association between CNVs and production traits in sheep. To the best of our knowledge, this is the first GWAS of CNVs and milk production traits in dairy sheep breed. Our results indicate that many CNVRs are associated with one or more milk production traits, and probably contribute to phenotypic variation. In particular, the two most significant CNVRs (p-value = 2.49E-14) located on chromosome 19 and associated with MY will be more investigated.




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