This tutorial covers a basic workflow for whole genome cnv analysis and association testing using the univariate segmentation process in svs. A statistical framework for performing casecontrol cnv association studies that applies likelihood ratio testing of quantitative cnv measurements in cases and controls. Cnvassociation metaanalysis in 191,161 european adults reveals. Highdensity single nucleotide polymorphism snp genotyping arrays recently have been used for copy number variation cnv detection and analysis, because the arrays can serve a dual role for snp and. This includes functionality for summarizing individual cnv calls across a population, assessing overlap with. While efficient for large cnv detection, genotyping arrays are less sensitive for detecting cnvs smaller than 50 kilobases. With wholegenome snp analysis, the snp array has become a method to measure copy. The go analysis identified possible candidate genes and pathways related to the. Copy number variation cnv is an important type of genetic variation contributing to phenotypic differences among mammals and may serve as an alternative molecular marker to single. Here we present a largescale cnv association metaanalysis on.
Cnvtools can model large batch effects that do not follow group membership, which is an important consideration in largescale association studies. Genomewide, imputed, sequence, and structural data are now available for exceedingly large sample sizes. Cnvs have successfully provided target genome regions for some disease. Understanding manhattan plots and genomewide association studies duration. I found this software called mrcanavar, and its great since it has its own aligner which is supposed to be designed specifically for cnv detection. Plink is a free, opensource whole genome association analysis toolset, designed to perform a range of basic, largescale analyses in a computationally efficient manner the focus of plink is purely on. A copy number variationbased casecontrol association. The purpose of this study was to analyze the cnv and its genetic effects of the opn4 gene in 284 guizhou goats guizhou black goat. It if often helpful to visually examine cnv calls to judge whether they are reliable or not.
The data is a formatted version of cnv calls that allow for cnv analysis in plink, and the phenotypes. The program features confidence threshold parameter, probe gap size threshold parameter, and more. Analysis of the association between cnvs and disease requires that. First, you need to find enriched cnv segments for each patient, using anytool. Copy number variants cnv are a potentially important component of the genetic contribution to risk of common complex diseases. Cnvranger provides downstream summarization and association analysis for cnv calls, it does not implement functions for cnv calling or quality control. Association tests and software for copy number variant data. Outputs from the 10 most common cnv defining algorithms can be directly used as input files for determining the three different definitions of cnvrs. Genomewide association studies gwas based on single. Gistic is normally used to find recurrent cnv among patients, and there are other tools as well to find recurrent cnvs. Single tube taqman copy number variation assays thermo. Cnvseq is a software to estimate copy number variation using nextgeneration sequence data.
Numerous studies have documented the role of copy number variations cnvs in human health with associated phenotypes including cancer, obesity, cognitive disability and numerous other. Analysis of the association between cnvs and disease requires that uncertainty in cnv copynumber calls, which can be substantial, be taken into account. Association analysis to copy number variation cnv of. The needs for data management, handling population structure and related. Cnvineta is an r package for mining and visualization of copy number variation cnv in casecontrol oligonucleotide array data, genotyped by single nucleotide polymorphism snp.
Office tools downloads illumina cnvpartition cnv analysis plugin by illumina, inc. Genomewide association study between cnvs and milk production. Cnvranger assumes cnv calls provided as input to be already filtered by quality, using the software that was used for cnv calling, or specific tools for that purpose. Reproductive performance of livestock is an economically important aspect of global food production. The tutorial is built around the affymetrix 500k array, but the. A novel querybased model matching regions to userdefined queries. After merging the overlapping cnvs using the cnvruler 42 software. Cnv association bioinformatics tools gwas analysis omicx. Genotyping console software thermo fisher scientific us. Using the softwares powerful numeric association testing and regression analysis capabilities, you can then perform association testing with these genebased covariates. By providing a basebybase view of the genome, ngs detects small or novel copy. Despite the fact that a plethora of software has been developed to detect.
Cnv analysis of meishan pig by nextgeneration sequencing. The parameters can be changed via an editable configuration file. Simplified oneclick export of summary calls text file with intensities for performing cnv analysis. Despite the importance and popularity of cnvphenotype association studies, there are not many algorithms that provide all three key steps mentioned above. Scientific protocols copy number variation detection via. Download illumina cnv analysis software for free windows. Access rights manager can enable it and security admins to quickly analyze user authorizations and access permission to systems, data, and files, and help them. The cnv association using a correlationtrend test model was. An intuitive graphical user interface gui enables the determination of cnv regions and carrying out association analysis through multiple regressions. Complete genomics cnv analysis pipeline employs readdepth analysis to estimate the genomic copy number at a given region based on the count of reads aligned to that region. Illumina cnvpartition cnv analysis plugin free download.
Germline copy number variations are associated with breast. To date, only one other r package, cnvtools, has been developed that can appropriately incorporate cnv copy number call uncertainty in the test for. After filtering, 27,200 cnvs remained for further analysis additional file 2. Conan is a crossplatform analysis software tool developed to provide several methods for genomewide association studies based on copy number variations. Methods for detecting cnv regions andor markers have the power to identify risk factors for disease directly. Genomewide association studies gwas using copy number variation cnv are becoming a central focus of genetic research. Association analysis to copy number variation cnv of opn4 gene with growth traits of goats by lijuan li 1, peng yang 2, shuyue shi 2, zijing zhang 3, qiaoting shi 3, jiawei xu 2, hua he 1,4. The microarrays and their defining features, including total probe numbers, types of probes, probe spacing across the genome, source of the raw data, platformspecific analysis software.
The chinese meishan pig is a prolific breed, with an average of three to five more piglets per litter than. The cnv association p value from the fisher exact test or lmm association analysis was assigned to the genes. Comprehensive performance comparison of highresolution. Software for computing and annotating genomic ranges. For genes that contain more than one cnv, multipletesting correction was.
Genomic copy number variation association study in. This document provides an overview on the usage of the cnvassoc. The cnvpartition cnv analysis plugin is a software library that works with illuminas genomestudio data analysis software. This includes functionality for summarizing individual cnv calls across a population, assessing overlap with functional genomic regions, and association analysis with gene expression and quantitative phenotypes.
Genes within significant associated cnvs for each trait were annotated. Association tests and software for copy number variant data ncbi. Similar to how genomewide association studies gwas have helped discover. Genomewide copy number variant analysis reveals variants. Copy number variation cnv is a major type of structural genomic. Cnv association testing a number of covariate generation procedures enable you to perform association testing on raw or pcacorrected log ratios, cnv segment means, and discretized values based on three and twostate models representing loss, neutral, and gain. After sample quality control, gene and cnvbased association tests were performed using cleaned data from group 1 493 cases and 1586 controls and group 2 307 cases and 1102 controls. The cnvranger package implements a comprehensive tool suite for cnv analysis. Cnvassoc allows users to perform association analysis between cnvs and disease incorporating uncertainty of cnv genotype. The cnvranger package implements association testing between cnv regions and rnaseq read counts based on edger robinson et al. Predesigned taqman copy number assays are ideal for analysis of copy number variation cnv and smaller regions in human and mouse genomes.
Integrated genotype calling and association analysis of snps, common copy number polymorphisms and rare cnvs. Wisard, a workbench for integrated superfast association study with related data is a statistical analysis toolkit for the analysis of largescale. Identification of snp markers for common cnv regions and. To date, only one other r package, cnvtools 5, has been developed that can appropriately incorporate cnv copy. Summarization and quantitative trait analysis of cnv ranges. Cnvruler is a userfriendly program with multiple functions that support all procedures of cnv phenotype association analysis in a single system without requiring any additional manual processes. Identification of breast cancer associated cnvs in coding regions. Copy number variation analysis cnv array and ngs solutions. The latest version of genotyping console software is supported on windows 7 64bit and windows 8. Association analysis of cnv data using r isaac subirana1,2,3, ramon diazuriarte4, gavin lucas2 and juan r gonzalez5,1 abstract background. This joint snpcnv association is implemented as part of the analysis software. Doing so manually in the illumina beadstudio software or the affymetrix genotyping console takes too much. The cnv association studies were performed with the golden helix svs 8.