Identity-by-Descent-Based Phasing and Imputation in Founder Populations Using Graphical Models

Accurate knowledge of haplotypes, the combination of alleles co‐residing on a single copy of a chromosome, enables powerful gene mapping and sequence imputation methods. Since humans are diploid, haplotypes must be derived from genotypes by a phasing process. In this study, we present a new computational model for haplotype phasing based on pairwise sharing of haplotypes inferred to be Identical‐By‐Descent (IBD). We apply the Bayesian network based model in a new phasing algorithm, called systematic long‐range phasing (SLRP), that can capitalize on the close genetic relationships in isolated founder populations, and show with simulated and real genome‐wide genotype data that SLRP substantially reduces the rate of phasing errors compared to previous phasing algorithms. Furthermore, the method accurately identifies regions of IBD, enabling linkage‐like studies without pedigrees, and can be used to impute most genotypes with very low error rate. Genet. Epidemiol. 2011.  © 2011 Wiley Periodicals, Inc.35:853‐860, 2011

• Publication year

  2011

• Venue

  Genetic Epidemiology

• Publication date

  2011-10-17

• Fields of study

  Biology, Medicine, Computer Science

• Identifiers
  DOI 10.1002/gepi.20635PMID 22006673PMCID 3368215
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Whole-genome molecular haplotyping of single cells

  2011cited by this paper
• A combined long-range phasing and long haplotype imputation method to impute phase for SNP genotypes

  2011cited by this paper
• A fast, powerful method for detecting identity by descent.

  2011cited by this paper
• Haplotype-resolved genome sequencing of a Gujarati Indian individual

  2011cited by this paper
• A rare variant in MYH6 is associated with high risk of sick sinus syndrome

  2011cited by this paper
• MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes

  2010influential reference
• High-resolution detection of identity by descent in unrelated individuals.

  2010cited by this paper
• Improved IBD detection using incomplete haplotype information

  2010cited by this paper
• Whole population, genome-wide mapping of hidden relatedness.

  2009influential reference
• A Flexible and Accurate Genotype Imputation Method for the Next Generation of Genome-Wide Association Studies

  2009cited by this paper
• Finding the missing heritability of complex diseases

  2009cited by this paper
• Systematic haplotype analysis resolves a complex plasma plant sterol locus on the Micronesian Island of Kosrae

  2009cited by this paper
• The Wellcome Trust Case Control Consortium, U.K.

  2008cited by this paper
• The genome-wide patterns of variation expose significant substructure in a founder population.

  2008cited by this paper
• Detection of sharing by descent, long-range phasing and haplotype imputation

  2008influential reference
• The IBD process along four chromosomes.

  2008cited by this paper
• Runs of homozygosity in European populations.

  2008cited by this paper
• Forward-time simulations of non-random mating populations using simuPOP

  2008cited by this paper
• PLINK: a tool set for whole-genome association and population-based linkage analyses.

  2007influential reference
• Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

  2007cited by this paper
• Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering.

  2007cited by this paper
• A second generation human haplotype map of over 3.1 million SNPs

  2007cited by this paper
• A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase.

  2006cited by this paper
• Efficiency and power in genetic association studies

  2005cited by this paper
• A Fine-Scale Map of Recombination Rates and Hotspots Across the Human Genome

  2005influential reference
• Low-Density Parity-Check Codes

  2004cited by this paper
• Haplotype reconstruction from genotype data using Imperfect Phylogeny

  2004cited by this paper
• Modeling linkage disequilibrium and identifying recombination hotspots using single-nucleotide polymorphism data.

  2003cited by this paper
• An MDL Method for Finding Haplotype Blocks and for Estimating the Strength of Haplotype Block Boundaries

  2002cited by this paper
• Genetic evidence for different male and female roles during cultural transitions in the British Isles

  2001cited by this paper
• Factor graphs and the sum-product algorithm

  2001influential reference
• Mapping quantitative trait loci in complex pedigrees: a two-step variance component approach.

  2000cited by this paper
• Loopy Belief Propagation for Approximate Inference: An Empirical Study

  1999cited by this paper
• Biological Sequence Analysis: Probabilistic Models of Proteins and Nucleic Acids

  1998cited by this paper
• Near Shannon limit error-correcting coding and decoding: Turbo-codes. 1

  1993cited by this paper
• Probabilistic reasoning in intelligent systems: Networks of plausible inference

  1991cited by this paper
• Probabilistic reasoning in intelligent systems - networks of plausible inference

  1989cited by this paper
• A Theory of Cooperative Phenomena

  1951cited by this paper

• Advances in haplotype phasing and genotype imputation

  2025cites this paper
• SURFBAT: a surrogate family based association test building on large imputation reference panels

  2023cites this paper
• Genome-wide association studies

  2021cites this paper
• Current Developments in Detection of Identity-by-Descent Methods and Applications

  2021cites this paper
• Off the street phasing (OTSP): no hassle haplotype phasing for molecular PGD applications

  2019cites this paper
• Haplotype Estimation and Genotype Imputation

  2019cites this paper
• Premutations in C9ORF72 and FMR1 in Iceland

  2019cites this paper
• Inter-individual genomic heterogeneity within European population isolates

  2019cites this paper
• Strategies for phasing and imputation in a population isolate

  2018cites this paper
• Non-parametric estimation of survival in age-dependent genetic disease and application to the transthyretin-related hereditary amyloidosis

  2018cites this paper
• Kinpute: Using identity by descent to improve genotype imputation

  2018cites this paper
• A comparison of different algorithms for phasing haplotypes using Holstein cattle genotypes and pedigree data.

  2017cites this paper
• Estimating genetic kin relationships in prehistoric populations

  2017cites this paper
• Computing Individual Risks Based on Family History in Genetic Disease in the Presence of Competing Risks

  2017cites this paper
• Université de Montréal-Thèse numérique

  2016influential citation
• Fast and accurate long-range phasing and imputation in a UK Biobank cohort

  2015cites this paper
• Fast and accurate long-range phasing in a UK Biobank cohort

  2015cites this paper
• Mountain gorilla genomes reveal the impact of long-term population decline and inbreeding

  2015cites this paper
• Identity-by-descent mapping in a Scandinavian multiple sclerosis cohort

  2014cites this paper
• A renewal theory approach to IBD sharing.

  2014cites this paper
• Recent identity by descent in human genetic data - methods and applications

  2014influential citation
• Identification of Genetic Determinants of Aging Traits

  2014cites this paper
• Using population isolates in genetic association studies

  2014cites this paper
• Origin of the PSEN1 E280A mutation causing early‐onset Alzheimer's disease

  2014cites this paper
• A General Approach for Haplotype Phasing across the Full Spectrum of Relatedness

  2014cites this paper
• Inferring the fine-scale structure and evolution of recombination from high-throughput genome sequencing

  2013cites this paper
• Improved whole-chromosome phasing for disease and population genetic studies

  2013cites this paper
• Imputation of Rare Variants in Next-Generation Association Studies

  2013cites this paper
• Imputation-based Assessment of Next Generation Rare Exome Variant Arrays

  2013cites this paper
• Reducing Pervasive False-Positive Identical-by-Descent Segments Detected by Large-Scale Pedigree Analysis

  2013cites this paper
• Inference of identity by descent in population isolates and optimal sequencing studies

  2013cites this paper
• Genome-wide patterns of identity-by-descent sharing in the French Canadian founder population

  2013cites this paper
• Improving the throughput of the forward population genetic simulation environment simuPOP

  2013cites this paper
• Supplementary Information for ‘ Improved whole chromosome phasing for disease and population genetic studies ’

  2012cites this paper
• Small effective population size and genetic homogeneity in the Val Borbera isolate

  2012cites this paper
• Quantifying recent variation and relatedness in human populations

  2012cites this paper
• The Variance of Identity-by-Descent Sharing in the Wright–Fisher Model

  2012influential citation