Nucleic Acids Research Advance Access originally published online on October 4, 2006
Nucleic Acids Research 2006 34(19):e129; doi:10.1093/nar/gkl700
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Nucleic Acids Research, 2006, Vol. 34, No. 19 e129
© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Using DNA pools for genotyping trios
Children's Hospital Oakland Research Institute 5700 Martin Luther King Jr Way, Oakland, CA 94609, USA 1 Sequenom, Inc. 3595 John Hopkins Court, San Diego, CA 92121, USA 2 Dx. Innovation, Inc. 3935 Lago di Grata Cir, San Diego, CA 92130, USA 3 International Computer Science Institute 1947 Center Street, Suite 600, Berkeley, CA 94704, USA
*To whom correspondence should be addressed. Tel: +1 510 666 2952; Fax: +1 510 666 2952; Email: heran{at}icsi.berkeley.edu
Received June 13, 2006. Revised August 17, 2006. Accepted September 5, 2006.
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.
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