| Copy number varairon (CNV) are DNA segments ranging from one kilobase (kb) to severalmegabase (Mb) in size deletions, insertions, duplications and complex multi-site variants. The lateststudies indicated that CNV distributed not only in human genome but also in other species. Due to CNVencompass more nucleotide content per genome than total SNPs (single nucleotide polymorphisms),and can influence gene expression, phenotypic variation and evolutionary adaptation by disruptinggenes and altering gene dosage. Therefore, CNV is increasingly considered to be an important andabundant source of genetic variation and phenotypic diversity. Furthermore, growth and developmenttraits in sheep are determined by the interactions between multiple genetic and environmental factors.Looking for differences in the phenotype diversity and discovering its corresponding genes have beenan important goal of sheep breeding. Among that, the study on the mechanism of CNV regulatingphenotype and disease is the focus area. At present, the combination of CNV and GWAS provides anovel way to explore the genetic bases of complex traits.This study employed whole genome genotyping using the ovine SNP50K BeadChip system tocharacterize the CNVs in the sheep genome, and the PennCNV software was used to identify the CNVin the sheep genome and constructed the first map of ovine CNV with whole genome SNP. After qualitycontrol, the results showed that a total of238high-confidence autosomal CNVRs were identified, whichincluded219losses,13gains, and6with both events (losses and gains), ranging from13.66kb to1.30Mb with a mean and median sizes of253.57and186.92kb, respectively, The distribution of CNVs insheep was nonrandomly distributed among different chromosomes. The most enriched chromosomes forCNVR in sheep were chromosomes1,2and5. Of the238CNVRs identified,75were present at afrequency>3%, Only2of75common CNPs were captured by at least one flanking SNP (r2>0.8),suggesting that the majority of the copy number polymorphisms were not well tagged by the nearbySNP on the illumina`s platform.GO analysis indicated that the most of genes overrepresented in DAVID were involved in olfactoryreceptor activity, sensory perception, cognition, G-protein coupled receptor protein activity,neurological system processes, and so on, The genes involved in environmental responses wereover-represented in the CNVR. In addition to evaluate the accuracy of the copy number assignments, weconducted quantitative-PCR (q-PCR) on ten selected CNVR, and five regions of these CNVR wereconfirmed in at least one of the animals tested. In summary, we anticipate that our results will be usefulin developing a fine-scale map of sheep CNV with functional genomic information, and may contributeto the determination of sheep genome architecture and diversity, to accelerate the advances in breedselection. In addition, these findings can be used to complement CNV maps in forming an exact globalCNV map, from which potential genetic markers may be developed to determine the roles of CNV insheep productive traits and evolutionary adaptation.To better understand the function of CNV in sheep production, we redefined the CNVR which were checked in previous analysis. We got402new CNVR, and143of which with a populationfrequency of more than3%is called CNP. Eleven traits, such as birth weight, adjusted125days weight(or weaning weight), adjusted190days weight (or six month weight), pre-weaning weight, post-weaningweight, daily weight gain, body height, chest girth, shin circumference to run CNVï¼GWAS.We used mixed linear model to run the CNP-GWAS of11phenotype traits, the results showed thatthere were32CNP significantly related to different traits on genome level(p<0.05). Of these CNP,5were related to birth weight,2were related to adjusted125days weight,9were related to adjusted190days weight,6were related to fat thickness,3were related to eye muscle area,3were related topre-weaning growth rate,8were related to post-weaning growth rate,10were related to daily weightgain,10were related to body height,5were related to chest girth,5were related to shin circumferencetrait. Besides the post-weaning growth rate, the others were not significant on genome level by FDR(false discovery rate). In addition, most CNP affected more than one trait, and some traits were relatedto several CNV regions. The above results indicated that some traits were affected by moreminor-polygene, and there was a certain genetic correlation between these traits.We found that CNP-210which located at52,788,004bp to52,907,062bp on sheep chromosome21was significantly related to adjusted125days weight(or weaning weight), adjusted190days weight（orsix months weight）, pre-weaning growth rate and daily weight gain, body height. Especially, theNADSYN1and MRGPRG genes in this area may play an important role in the sheep production. We alsofound that, the most significant CNP-393upstream, namely the TRHR gene at76,545,109~76,642,439upstream4.5Mb of chromosome9, may be affected the skeletal muscle development, and lamb growth.Present study demonstrates that CNP-210and CNP-393may be two genetic variations affecting lambgrowth and development area, and can be further studied and analyzed as candidate regions.In summary, the CNV analysis of sheep genome provides a new idea to understand the geneticbasis of sheep complex traits. Based on these results, it is useful to study the sheep genomecharacteristics in the following. In addition, it supplies us the important information of genetic variationmechanism in sheep growth... |
