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Using DNA pools for genotyping trios
The genotyping of mother–father–child trios is a very useful tool in disease association studies, as trios eliminate population stratification effects and increase the accuracy of haplotype inference. Unfortunately, the use of trios for association studies may reduce power, since it requires the gen...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1636483/ https://www.ncbi.nlm.nih.gov/pubmed/17020923 http://dx.doi.org/10.1093/nar/gkl700 |
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author | Beckman, Kenneth B. Abel, Kenneth J. Braun, Andreas Halperin, Eran |
author_facet | Beckman, Kenneth B. Abel, Kenneth J. Braun, Andreas Halperin, Eran |
author_sort | Beckman, Kenneth B. |
collection | PubMed |
description | The genotyping of mother–father–child trios is a very useful tool in disease association studies, as trios eliminate population stratification effects and increase the accuracy of haplotype inference. Unfortunately, the use of trios for association studies may reduce power, since it requires the genotyping of three individuals where only four independent haplotypes are involved. We describe here a method for genotyping a trio using two DNA pools, thus reducing the cost of genotyping trios to that of genotyping two individuals. Furthermore, we present extensions to the method that exploit the linkage disequilibrium structure to compensate for missing data and genotyping errors. We evaluated our method on trios from CEPH pedigree 66 of the Coriell Institute. We demonstrate that the error rates in the genotype calls of the proposed protocol are comparable to those of standard genotyping techniques, although the cost is reduced considerably. The approach described is generic and it can be applied to any genotyping platform that achieves a reasonable precision of allele frequency estimates from pools of two individuals. Using this approach, future trio-based association studies may be able to increase the sample size by 50% for the same cost and thereby increase the power to detect associations. |
format | Text |
id | pubmed-1636483 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-16364832006-11-29 Using DNA pools for genotyping trios Beckman, Kenneth B. Abel, Kenneth J. Braun, Andreas Halperin, Eran Nucleic Acids Res Methods Online The genotyping of mother–father–child trios is a very useful tool in disease association studies, as trios eliminate population stratification effects and increase the accuracy of haplotype inference. Unfortunately, the use of trios for association studies may reduce power, since it requires the genotyping of three individuals where only four independent haplotypes are involved. We describe here a method for genotyping a trio using two DNA pools, thus reducing the cost of genotyping trios to that of genotyping two individuals. Furthermore, we present extensions to the method that exploit the linkage disequilibrium structure to compensate for missing data and genotyping errors. We evaluated our method on trios from CEPH pedigree 66 of the Coriell Institute. We demonstrate that the error rates in the genotype calls of the proposed protocol are comparable to those of standard genotyping techniques, although the cost is reduced considerably. The approach described is generic and it can be applied to any genotyping platform that achieves a reasonable precision of allele frequency estimates from pools of two individuals. Using this approach, future trio-based association studies may be able to increase the sample size by 50% for the same cost and thereby increase the power to detect associations. Oxford University Press 2006-11 2006-10-04 /pmc/articles/PMC1636483/ /pubmed/17020923 http://dx.doi.org/10.1093/nar/gkl700 Text en © 2006 The Author(s) |
spellingShingle | Methods Online Beckman, Kenneth B. Abel, Kenneth J. Braun, Andreas Halperin, Eran Using DNA pools for genotyping trios |
title | Using DNA pools for genotyping trios |
title_full | Using DNA pools for genotyping trios |
title_fullStr | Using DNA pools for genotyping trios |
title_full_unstemmed | Using DNA pools for genotyping trios |
title_short | Using DNA pools for genotyping trios |
title_sort | using dna pools for genotyping trios |
topic | Methods Online |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1636483/ https://www.ncbi.nlm.nih.gov/pubmed/17020923 http://dx.doi.org/10.1093/nar/gkl700 |
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