Fast and accurate genotype imputation for nonmodel. Imputation page at wikipedia will be a nice start to understand the concept of imputation from a genotyping perspective, it refers to the imputation snps that are not directly genotyped on your genotyping platform for example. To this end, genotypes that have not been measured in a given cohort can be imputed on the basis of a set of reference haplotypes. Genotype imputation performance of three reference panels. Summary an interface package for genotype imputation, phasing and computation of genotyping accuracy. Gigi is a computer program to impute missing genotypes on pedigrees. Using imputation, researchers can evaluate and compare data from different providers or genotype chip versions in a more standardised format. Most existing genotype imputation methods, such as beagle browning and.
Genotype imputation in studies of related individuals family samples constitute the most intuitive setting for genotype imputation. Pedigree information becomes more important as the low density panel becomes sparser. Maximizing genetic similarity between study sample and intended reference panels may. Imputation in genetics refers to the statistical inference of unobserved genotypes. General imputation softwares to impute missing genotypes. Therefore, key components for a successful imputation include not only a promising imputation method but also an appropriate reference panel. Genotype imputation is now an essential tool in the analysis of genomewide association scans. I know that we can impute missing genotypes in gwas studies by inferring from the hapmap or genomes genotypes. Privacy policy about wikipedia disclaimers contact wikipedia developers statistics cookie statement mobile view. In this study, our goal was to examine two highly popular genotype imputation software packages, impute v2 and. Barrett, group leader, wellcome trust sanger institute. This tutorials are not specific to your population of interest, but you can adapt them for your requirement. Regardless of what software or reference sets are used to generate. Genotype imputation is particularly useful for combining results across studies that rely on different genotyping platforms but also increases the power.
Genotype imputation in studies of related individuals. Genotype imputation software tools genomewide association. Analyses of genomewide association studies contributed by dr. Genotype imputation is a common technique in genetic research. Genotypes for a relatively modest number of genetic markers can be used to identify long stretches of haplotype shared between individuals of known relationship.
Genotype imputation software tools genomewide association study data analysis genotype imputation has been widely adopted in the postgenomewide association studies gwas era. For example, many studies use data from the ukbiobank which uses a chip made by the company affymetrix as well as data from 23andme which has used multiple different chips over the past decade made by the. Genotype imputation is a statistical approach that can be used in. This protocol describes how to perform snp imputations for gwas metaanalysis with the genome of the netherlands reference panel using minimac or impute2. Here we introduce linkimpute, a software package based on a knearest. Hint a plink binary fileset of the phase 2 hapmap data can be downloaded from here. Software tools institute for quantitative and computational. In our experience, userfriendliness is often the deciding. Current software for genotype imputation springerlink.
An excellent discussion of genotype imputation enables powerful combined analyses of genomewide association studies. Our imputation and haplotypeinference methods are implemented in version 3. The genotype assembly will be included in the reference file, if add to reference panels folder is selected. This protocol provides guidelines for performing imputations with. Genotype imputation in families suppose a particular genotype g ij is missing genotype for person i at marker j consider full set of observed genotypes g evaluate pedigree likelihood l for each combination of g, g ij x posterior probability that g ij x is. This approach has been used to impute sporadic missing snp genotype. Genotype imputation is used to estimate unobserved genotypes from genomewide maker data, to increase genome coverage and power for genomewide association studies. The raw data consists of a set of genotyped snps with a large number of snps without any genotype data a. Genotypes for a relatively modest number of genetic markers can be used to identify long stretches of haplotype. Nov 01, 2011 genotype imputation is a statistical technique that is often used to increase the power and resolution of genetic association studies. Metaanalysis of multiple study datasets also requires a substantial overlap of snps for a successful association analysis, which can be achieved by imputation. I have a few questions regarding genotype imputation using beagle. Imputation has been most successful for european ancestry populations in which very large reference panels are available.
Genotype imputation, used in genomewide association studies to. There are a number of distinct scenarios in which genotype imputation is desirable, but the term now most often refers to the situation in which a reference panel of haplotypes at a dense set. The service pipeline uses eagle2 or shapeit2 for prephasing, eagle2 for phasing, and pbwt positional burrowswheeler transform for genotype imputation. The hapseqx algorithm uses a combination of dynamic programming and a hidden. A coalescent model for genotype imputation genetics. Genotype imputation to improve the costefficiency of genomic. The effect of reference datasets and software tools on. We develop cutting edge quantitative and computational tools ranging from statistical analysis and modeling approaches to physicsbased algorithms and mechanistic modeling. New methods for imputation of missing genotype using linkage. Jun 17, 2014 genotype imputation can help reduce genotyping costs particularly for implementation of genomic selection.
Aug 01, 2012 genotype imputation is a valuable tool in genetic studies of complex disease, and optimizing imputation accuracy is important for conducting analyses with imputed data. Quality of imputed datasets is largely dependent on the software used, as well as the reference populations. Imputation attempts to predict these missing genotypes. These data are publicly available from the hapmap web site, and population cohorts from these data can be used as reference panels in beagle for genotype imputation. Genotype imputation assessment of the uk biobank array for imputation the uk biobank axiom array from affymetrix was specifically designed to optimize imputation performance in gwas studies 6. Current software for genotype imputation david ellinghaus 1 stefan schreiber 1 andre franke 1 michael nothnagel 0 0 institute of medical informatics and statistics, christianalbrechts university, kiel, germany 1 institute of clinical molecular biology, christianalbrechts university, kiel, germany genotype imputation for single nucleotide polymorphisms snps has been shown to be a. Genotype imputation has been widely adopted in the postgenomewide association studies gwas era. A unified approach to genotype imputation and haplotype. Accurate genotype imputation in multiparental populations. Impact of genetic similarity on imputation accuracy bmc. The figure illustrates the idea of genotype imputation in a sample of unrelated individuals.
N2 application of imputation methods to accurately predict a dense array of snp genotypes in the dog could provide an important supplement to current analyses of arraybased genotyping data. Sep 01, 2018 many different types of multiparental populations have recently been produced to increase genetic diversity and resolution in qtl mapping. To create a reference panel, go to genotype create imputation reference panel from your quality filtered genotype spreadsheet. Comprehensive assessment of genotype imputation performance. Genotypes for a relatively modest number of genetic. A new approach for efficient genotype imputation using. Current software for genotype imputation human genomics. Major milestones estimation of missing data is a ubiquitous problem in statistics, and human genetic studies are no exception. The unphased program implements an unpublished method for genotype imputation in nuclear families. Lowcoverage, genotypingbysequencing gbs technology has become a costeffective tool in these populations, despite large amounts of missing data in offspring and founders. Mach developers have announced that they will share their sources at some point in the future. Genotype imputation is the term used to describe the process of predicting or imputing genotypes that are not directly assayed in a sample of individuals.
Evaluating the accuracy of imputation methods in a five. Genotype imputation for single nucleotide polymorphisms snps has been shown to be a powerful means to include genetic markers in exploratory genetic association studies without having to genotype them, and is becoming a standard procedure. A variety of modern software packages are available for genotype. At first, we get haplotypes of each samples from their genotype data using plem partitionligation expectation maximization except for the samples which have the missing elements in their genotypes like as fig. These challenges necessitated the development of statistical methods and. The process makes it relatively straightforward to combine results of genomewide association scans based on different genotyping platforms for two early examples of how the process works, see the papers by willer et al nat genet, 2008 and sanna et. Imputation methods work by using haplotype patterns in a reference panel to predict unobserved genotypes in a study dataset, and a number of approaches have been proposed for choosing subsets of reference haplotypes that will maximize accuracy in a given study. Pdf current software for genotype imputation michael. Assessment of genotype imputation performance using.
Genotype imputation has been used widely in the analysis of gwa studies to boost. A number of different software programs are available for genotype imputation, so the researcher must decide which program to use. Genotype imputation is a powerful tool for increasing statistical power in an. Current software for genotype imputation pdf paperity. Family samples constitute the most intuitive setting for genotype imputation. Many different types of multiparental populations have recently been produced to increase genetic diversity and resolution in qtl mapping. The process makes it relatively straightforward to combine results of genomewide association scans based on different genotyping platforms for two early examples of how the process works, see the papers by. Jul 30, 2015 this protocol describes how to perform snp imputations for gwas metaanalysis with the genome of the netherlands reference panel using minimac or impute2. Genotype imputation for genomewide association studies.
Hibag can be used by researchers with published parameter estimates instead of requiring access to large training sample datasets. Hla genotype imputation with attribute bagging github. Depending on the type of genetic study, there are two approaches for doing genotype imputation. Imputation methods work by using haplotype patterns in a reference panel to predict unobserved genotypes in a study dataset, and a number of approaches have been proposed for choosing subsets of reference haplotypes that will.
Genotype imputation can help reduce genotyping costs particularly for implementation of genomic selection. Summary an interface package for genotype imputation, phasing and. We assume that the hapmap ceu founders will be used in this example. Popular imputation methods are based upon the hidden markov model and have. The probabilities are useful as an input for genotype imputation software. Maximizing genetic similarity between study sample. Genotype imputation enables powerful combined analyses of. Genotype imputation is particularly useful for combining results across studies that rely on different genotyping platforms but also increases the power of. Imputation of missing genotypes is becoming a very popular solution for synchronizing genotype data collected with different microarray platforms but the effect of ethnic background, subject ascertainment, and amount of missing data on the accuracy of imputation are not well understood. A number of different software programs are available. This is a list of notable software for haplotype estimation and genotype imputation.
This technique allows geneticists to accurately evaluate the evidence for association at genetic markers that are not directly genotyped. Genotype imputation is a valuable tool in genetic studies of complex disease, and optimizing imputation accuracy is important for conducting analyses with imputed data. Quality of imputed datasets is largely dependent on the software used. Here we introduce linkimpute, a software package based on a knearest neighbor genotype imputation method, ldknni, which is designed for unordered markers. Genotype imputation is a costeffective method for obtaining highdensity genotypes, but its value in aquaculture breeding programs which are characterised by large fullsibling families has yet. Genotype imputation is a process of estimating missing genotypes from. Comparing performance of modern genotype imputation methods in. Genotype imputation to improve the costefficiency of. Frontiers evaluating the accuracy of imputation methods. Perhaps the reason that most people use of mach is to infer genotypes at untyped markers in genomewide association scans. In this work, we present a general statistical framework for genotype imputation. No physical or genetic maps are required, and it is designed to work on unphased genotype data from heterozygous species. Although several reference panels are available, it is often not clear which is the most optimal for a particular target dataset to be imputed.
This body of work focuses on assessing imputation accuracy and uses imputed data to identify genetic contributors to. However, candidate gene studies can not use this method. Current software for genotype imputation david ellinghaus 1 stefan schreiber 1 andre franke 1 michael nothnagel 0 0 institute of medical informatics and statistics, christianalbrechts university, kiel, germany 1 institute of clinical molecular biology, christianalbrechts university, kiel, germany genotype imputation for single nucleotide polymorphisms snps has been. Sanger genotype imputation and phasing service is a webbased tool at wellcome sanger institute. Genotype imputation has become a standard tool in genomewide association. The formulas we have derived are a step toward the development of more complicated models that can be used to make practical quantitative predictions about imputation accuracy. Can anyone post here an example of a genotype imputation commnad line. Genetic similarity between target population and reference dataset is crucial for highquality results.
Genotype imputation is a statistical technique that is often used to increase the power and resolution of genetic association studies. Testing for association at just these snps may not lead to a significant association b. I would like to point you to tutorials on how to use plink or mach or impute for genotype imputation, these tools widely used for this type of analysis. Genotype imputation, the process of inferring genotypes for untyped variants, is used to identify and refine genetic association findings. It is achieved by using known haplotypes in a population, for instance from the hapmap or the genomes project in humans, thereby allowing to test for association between a trait of interest e. Genotype imputation and genetic association studies of uk.
Genotype imputation, also called insilico genotyping, is a costeffective and efficient way to maximize genome coverage in an association study for little or no additional cost. An experiment was carried out to assess the imputation performance of the array, stratified by allele frequency, and to. Qcb encompasses a broad range of quantitative and computational biosciences research. Genotype imputation is an important tool for genomewide association studies as it increases power, aids in finemapping of associations and facilitates metaanalyses. In applications entailing large populations, recovering the genotypes of untyped loci using information from reference individuals that were genotyped with a higher density panel is computationally challenging. Note that if pedigree information is provided fimpute makes use of this information for more accurate imputation. Genotype imputation traditionally is a procedure of inferring the small. There is therefore a need for imputation methods designed specifically for nonmodel organisms in which genomic resources are poorly developed and marker order is unreliable or unknown.
Our approach handles large pedigrees by using a markov chain monte carlobased program to infer inheritance vectors. Owing to its ability to accurately predict the genotypes of untyped variants, imputation greatly boosts variant density, allowing finemapping studies of gwas loci and largescale metaanalysis across different genotyping arrays. I am very new in the bioninformatics field, so forgive me if i am asking any dumb questions. Select from the provided options or keep the defaults and select run. Mach, beagle, or provide specially designed file format conversion tools e. This gives promise to the development of nlp methods in comparing go terms. Basic steps for using plink imputation functions the first step is to create a single fileset with the reference panel merged in with your dataset.
High input genotype quality is the key for accurate imputation with fimpute. Genotype imputation is used to estimate unobserved genotypes from genomewide maker data, to increase genome coverage and power for genomewide association. In our experience, userfriendliness is often the deciding factor in the choice of software to. Gigi genotype imputation given inheritance introduction. Jul 22, 2015 genotype imputation is a common technique in genetic research. Genotype imputation is a powerful tool for increasing statistical power in an association analysis. Hibag is a state of the art software package for imputing hla types using snp data, and it relies on a training set of hla and snp genotypes.
Genotype imputation for genomewide association studies jonathan marchini and bryan howie abstract in the past few years genomewide association gwa studies have uncovered a large number of convincingly replicated associations for many complex human diseases. Imputation estimates genotypes at ungenotyped loci imputation algorithms enable genotype data estimation between marker sets with different content using the inherent correlation of snps in linkage disequilibrium ld haplotype blocks. Populationspecific genotype imputations using minimac or. However the advent of gwass ushered in a new era, with a new type of imputation. List of haplotype estimation and genotype imputation software. Genotype imputation methods and their effects on genomic. The performance of genomic prediction using imputed genotype data was comparable to using true genotype data.
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