Dataset Information

Copy number variants in the sheep genome detected using multiple approaches.

ABSTRACT: Copy number variants (CNVs) are a type of polymorphism found to underlie phenotypic variation, both in humans and livestock. Most surveys of CNV in livestock have been conducted in the cattle genome, and often utilise only a single approach for the detection of copy number differences. Here we performed a study of CNV in sheep, using multiple methods to identify and characterise copy number changes. Comprehensive information from small pedigrees (trios) was collected using multiple platforms (array CGH, SNP chip and whole genome sequence data), with these data then analysed via multiple approaches to identify and verify CNVs.In total, 3,488 autosomal CNV regions (CNVRs) were identified in this study, which substantially builds on an initial survey of the sheep genome that identified 135 CNVRs. The average length of the identified CNVRs was 19 kb (range of 1 kb to 3.6 Mb), with shorter CNVRs being more frequent than longer CNVRs. The total length of all CNVRs was 67.6Mbps, which equates to 2.7 % of the sheep autosomes. For individuals this value ranged from 0.24 to 0.55 %, and the majority of CNVRs were identified in single animals. Rather than being uniformly distributed throughout the genome, CNVRs tended to be clustered. Application of three independent approaches for CNVR detection facilitated a comparison of validation rates. CNVs identified on the Roche-NimbleGen 2.1M CGH array generally had low validation rates with lower density arrays, while whole genome sequence data had the highest validation rate (>60 %).This study represents the first comprehensive survey of the distribution, prevalence and characteristics of CNVR in sheep. Multiple approaches were used to detect CNV regions and it appears that the best method for verifying CNVR on a large scale involves using a combination of detection methodologies. The characteristics of the 3,488 autosomal CNV regions identified in this study are comparable to other CNV regions reported in the literature and provide a valuable and sizeable addition to the small subset of published sheep CNVs.

SUBMITTER: Jenkins GM

PROVIDER: S-EPMC4898393 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Copy number variants in the sheep genome detected using multiple approaches.

Jenkins Gemma M GM Goddard Michael E ME Black Michael A MA Brauning Rudiger R Auvray Benoit B Dodds Ken G KG Kijas James W JW Cockett Noelle N McEwan John C JC

BMC genomics 20160608

<h4>Background</h4>Copy number variants (CNVs) are a type of polymorphism found to underlie phenotypic variation, both in humans and livestock. Most surveys of CNV in livestock have been conducted in the cattle genome, and often utilise only a single approach for the detection of copy number differences. Here we performed a study of CNV in sheep, using multiple methods to identify and characterise copy number changes. Comprehensive information from small pedigrees (trios) was collected using mul ...[more]

PMID: 27277319

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Project description:BACKGROUND: In recent years, genome-wide association studies have successfully uncovered single-nucleotide polymorphisms (SNPs) associated with complex traits such as diseases and quantitative phenotypes. These variations account for a small proportion of heritability. With the development of high throughput techniques, abundant submicroscopic structural variations have been found in organisms, of which the main variations are copy number variations (CNVs). Therefore, CNVs are increasingly recognized as an important and abundant source of genetic variation and phenotypic diversity. RESULTS: Analyses of CNVs in the genomes of three sheep breeds were performed using the Ovine SNP50 BeadChip array. A total of 238 CNV regions (CNVRs) were identified, including 219 losses, 13 gains, and six with both events (losses and gains), which cover 60.35 Mb of the sheep genomic sequence and correspond to 2.27% of the autosomal genome sequence. The length of the CNVRs on autosomes range from 13.66 kb to 1.30 Mb with a mean size of 253.57 kb, and 75 CNVRs events had a frequency > 3%. Among these CNVRs, 47 CNVRs identified by the PennCNV overlapped with the CNVpartition. Functional analysis indicated that most genes in the CNVRs were significantly enriched for involvement in the environmental response. Furthermore, 10 CNVRs were selected for validation and 6 CNVRs were further experimentally confirmed by qPCR. In addition, there were 57 CNVRs overlapped in our new dataset and other published ruminant CNV studies. CONCLUSIONS: In this study, we firstly constructed a sheep CNV map based on the Ovine SNP50 array. Our results demonstrated the differences of two detection tools and integration of multiple algorithms can enhance the detection of sheep genomic structure variations. Furthermore, our findings would be of help for understanding the sheep genome and provide preliminary foundation for carrying out the CNVs association studies with economically important phenotypes of sheep in the future.

Project description:BackgroundCopy number variation (CNV) is an important source of structural variation in the mammalian genome. CNV assays present a new method to explore the genomic diversity of environmental adaptations in animals and plants and genes associated with complex traits. In this study, the genome-wide CNV distribution characteristics of 20 Tibetan sheep from two breeds (10 Oula sheep and 10 Panou sheep) were analysed using whole-genome resequencing to investigate the variation in the genomic structure of Tibetan sheep during breeding.ResultsCNVs were detected using CNVnator, and the overlapping regions of CNVs between individual sheep were combined. Among them, a total of 60,429 CNV events were detected between the indigenous sheep breed (Oula) and the synthetic sheep breed (Panou). After merging the overlapping CNVs, 4927 CNV regions (CNVRs) were finally obtained. Of these, 4559 CNVRs were shared by two breeds, and there were 368 differential CNVRs. Deletion events have a higher percentage of occurrences than duplication events. Functional enrichment analysis showed that the shared CNVRs were significantly enriched in 163 GO terms and 62 KEGG pathways, which were mainly associated with organ development, neural regulation, immune regulation, digestion and metabolism. In addition, 140 QTLs overlapped with some of the CNVRs at more than 1 kb, such as average daily gain QTL, body weight QTL, and total lambs born QTL. Many of the CNV-overlapping genes such as PPP3CA, SSTR1 and FASN, overlap with the average daily weight gain and carcass weight QTL regions. Moreover, VST analysis showed that XIRP2, ABCB1, CA1, ASPA and EEF2 differed significantly between the synthetic breed and local sheep breed. The duplication of the ABCB1 gene may be closely related to adaptation to the plateau environment in Panou sheep, which deserves further study. Additionally, cluster analysis, based on all individuals, showed that the CNV clustering could be divided into two origins, indicating that some Tibetan sheep CNVs are likely to arise independently in different populations and contribute to population differences.ConclusionsCollectively, we demonstrated the genome-wide distribution characteristics of CNVs in Panou sheep by whole genome resequencing. The results provides a valuable genetic variation resource and help to understand the genetic characteristics of Tibetan sheep. This study also provides useful information for the improvement and breeding of Tibetan sheep in the future.

Project description:The requirement for large amounts of good quality DNA for whole-genome applications prohibits their use for small, laser capture micro-dissected (LCM), and/or rare clinical samples, which are also often formalin-fixed and paraffin-embedded (FFPE). Whole-genome amplification of DNA from these samples could, potentially, overcome these limitations. However, little is known about the artefacts introduced by amplification of FFPE-derived DNA with regard to genotyping, and subsequent copy number and loss of heterozygosity (LOH) analyses. Using a ligation adaptor amplification method, we present data from a total of 22 Affymetrix SNP 6.0 experiments, using matched paired amplified and non-amplified DNA from 10 LCM FFPE normal and dysplastic oral epithelial tissues, and an internal method control. An average of 76.5% of SNPs were called in both matched amplified and non-amplified DNA samples, and concordance was a promising 82.4%. Paired analysis for copy number, LOH, and both combined, showed that copy number changes were reduced in amplified DNA, but were 99.5% concordant when detected, amplifications were the changes most likely to be 'missed', only 30% of non-amplified LOH changes were identified in amplified pairs, and when copy number and LOH are combined ?50% of gene changes detected in the unamplified DNA were also detected in the amplified DNA and within these changes, 86.5% were concordant for both copy number and LOH status. However, there are also changes introduced as ?20% of changes in the amplified DNA are not detected in the non-amplified DNA. An integrative network biology approach revealed that changes in amplified DNA of dysplastic oral epithelium localize to topologically critical regions of the human protein-protein interaction network, suggesting their functional implication in the pathobiology of this disease. Taken together, our results support the use of amplification of FFPE-derived DNA, provided sufficient samples are used to increase power and compensate for increased error rates.

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Copy number variants in the sheep genome detected using multiple approaches.

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Copy number variants in the sheep genome detected using multiple approaches.

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