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Detection of recombination events, haplotype reconstruction and imputation of sires using half-sib SNP genotypes

BACKGROUND: Identifying recombination events and the chromosomal segments that constitute a gamete is useful for a number of applications in genomic analyses. In livestock, genotypic data are commonly available for half-sib families. We propose a straightforward but computationally efficient method...

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Autores principales: Ferdosi, Mohammad H, Kinghorn, Brian P, van der Werf, Julius H J, Gondro, Cedric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996164/
https://www.ncbi.nlm.nih.gov/pubmed/24495596
http://dx.doi.org/10.1186/1297-9686-46-11
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author Ferdosi, Mohammad H
Kinghorn, Brian P
van der Werf, Julius H J
Gondro, Cedric
author_facet Ferdosi, Mohammad H
Kinghorn, Brian P
van der Werf, Julius H J
Gondro, Cedric
author_sort Ferdosi, Mohammad H
collection PubMed
description BACKGROUND: Identifying recombination events and the chromosomal segments that constitute a gamete is useful for a number of applications in genomic analyses. In livestock, genotypic data are commonly available for half-sib families. We propose a straightforward but computationally efficient method to use single nucleotide polymorphism marker genotypes on half-sibs to reconstruct the recombination and segregation events that occurred during meiosis in a sire to form the haplotypes observed in its offspring. These meiosis events determine a block structure in paternal haplotypes of the progeny and this can be used to phase the genotypes of individuals in single half-sib families, to impute haplotypes of the sire if they are not genotyped or to impute the paternal strand of the offspring’s sequence based on sequence data of the sire. METHODS: The hsphase algorithm exploits information from opposing homozygotes among half-sibs to identify recombination events, and the chromosomal regions from the paternal and maternal strands of the sire (blocks) that were inherited by its progeny. This information is then used to impute the sire’s genotype, which, in turn, is used to phase the half-sib family. Accuracy (defined as R(2)) and performance of this approach were evaluated by using simulated and real datasets. Phasing results for the half-sibs were benchmarked to other commonly used phasing programs – AlphaPhase, BEAGLE and PedPhase 3. RESULTS: Using a simulated dataset with 20 markers per cM, and for a half-sib family size of 4 and 40, the accuracy of block detection, was 0.58 and 0.96, respectively. The accuracy of inferring sire genotypes was 0.75 and 1.00 and the accuracy of phasing was around 0.97, respectively. hsphase was more robust to genotyping errors than PedPhase 3, AlphaPhase and BEAGLE. Computationally, hsphase was much faster than AlphaPhase and BEAGLE. CONCLUSIONS: In half-sib families of size 8 and above, hsphase can accurately detect block structure of paternal haplotypes, impute genotypes of ungenotyped sires and reconstruct haplotypes in progeny. The method is much faster and more accurate than other widely used population-based phasing programs. A program implementing the method is freely available as an R package (hsphase).
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spelling pubmed-39961642014-05-07 Detection of recombination events, haplotype reconstruction and imputation of sires using half-sib SNP genotypes Ferdosi, Mohammad H Kinghorn, Brian P van der Werf, Julius H J Gondro, Cedric Genet Sel Evol Research BACKGROUND: Identifying recombination events and the chromosomal segments that constitute a gamete is useful for a number of applications in genomic analyses. In livestock, genotypic data are commonly available for half-sib families. We propose a straightforward but computationally efficient method to use single nucleotide polymorphism marker genotypes on half-sibs to reconstruct the recombination and segregation events that occurred during meiosis in a sire to form the haplotypes observed in its offspring. These meiosis events determine a block structure in paternal haplotypes of the progeny and this can be used to phase the genotypes of individuals in single half-sib families, to impute haplotypes of the sire if they are not genotyped or to impute the paternal strand of the offspring’s sequence based on sequence data of the sire. METHODS: The hsphase algorithm exploits information from opposing homozygotes among half-sibs to identify recombination events, and the chromosomal regions from the paternal and maternal strands of the sire (blocks) that were inherited by its progeny. This information is then used to impute the sire’s genotype, which, in turn, is used to phase the half-sib family. Accuracy (defined as R(2)) and performance of this approach were evaluated by using simulated and real datasets. Phasing results for the half-sibs were benchmarked to other commonly used phasing programs – AlphaPhase, BEAGLE and PedPhase 3. RESULTS: Using a simulated dataset with 20 markers per cM, and for a half-sib family size of 4 and 40, the accuracy of block detection, was 0.58 and 0.96, respectively. The accuracy of inferring sire genotypes was 0.75 and 1.00 and the accuracy of phasing was around 0.97, respectively. hsphase was more robust to genotyping errors than PedPhase 3, AlphaPhase and BEAGLE. Computationally, hsphase was much faster than AlphaPhase and BEAGLE. CONCLUSIONS: In half-sib families of size 8 and above, hsphase can accurately detect block structure of paternal haplotypes, impute genotypes of ungenotyped sires and reconstruct haplotypes in progeny. The method is much faster and more accurate than other widely used population-based phasing programs. A program implementing the method is freely available as an R package (hsphase). BioMed Central 2014-02-04 /pmc/articles/PMC3996164/ /pubmed/24495596 http://dx.doi.org/10.1186/1297-9686-46-11 Text en Copyright © 2014 Ferdosi et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Ferdosi, Mohammad H
Kinghorn, Brian P
van der Werf, Julius H J
Gondro, Cedric
Detection of recombination events, haplotype reconstruction and imputation of sires using half-sib SNP genotypes
title Detection of recombination events, haplotype reconstruction and imputation of sires using half-sib SNP genotypes
title_full Detection of recombination events, haplotype reconstruction and imputation of sires using half-sib SNP genotypes
title_fullStr Detection of recombination events, haplotype reconstruction and imputation of sires using half-sib SNP genotypes
title_full_unstemmed Detection of recombination events, haplotype reconstruction and imputation of sires using half-sib SNP genotypes
title_short Detection of recombination events, haplotype reconstruction and imputation of sires using half-sib SNP genotypes
title_sort detection of recombination events, haplotype reconstruction and imputation of sires using half-sib snp genotypes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996164/
https://www.ncbi.nlm.nih.gov/pubmed/24495596
http://dx.doi.org/10.1186/1297-9686-46-11
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