Correcting estimators of theta and Tajima's D for ascertainment biases caused by the single-nucleotide polymorphism discovery process

Most single-nucleotide polymorphism (SNP) data suffer from an ascertainment bias caused by the process of SNP discovery followed by SNP genotyping. The final genotyped data are biased toward an excess of common alleles compared to directly sequenced data, making standard genetic methods of analysis...

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Bibliographic Details
Published in:Genetics (Austin) 2009-02, Vol.181 (2), p.701-710
Main Authors: Ramírez-Soriano, Anna, Nielsen, Rasmus
Format: Article
Language:English
Subjects:
Alleles
Analysis of Variance
Bias
Biometry
Computer Simulation
Databases, Genetic
Genetics, Population - statistics & numerical data
Genome, Human
Genotype
Humans
Investigations
Models, Genetic
Mutation
Polymorphism, Single Nucleotide
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Summary:Most single-nucleotide polymorphism (SNP) data suffer from an ascertainment bias caused by the process of SNP discovery followed by SNP genotyping. The final genotyped data are biased toward an excess of common alleles compared to directly sequenced data, making standard genetic methods of analysis inapplicable to this type of data. We here derive corrected estimators of the fundamental population genetic parameter = 4N(e)mu (N(e), effective population size; mu, mutation rate) on the basis of the average number of pairwise differences and on the basis of the number of segregating sites. We also derive the variances and covariances of these estimators and provide a corrected version of Tajima's D statistic. We reanalyze a human genomewide SNP data set and find substantial differences in the results with or without ascertainment bias correction.
ISSN:0016-6731
1943-2631
1943-2631
DOI:10.1534/genetics.108.094060